HEPATITIS

Diagnosis, Diagnostics, Immunodiagnosis & Immunodiagnostics:

3259. Akuta N. Chayama K. Suzuki F. Someya T. Kobayashi M. Tsubota A. Suzuki Y. Saitoh S. Arase Y. Ikeda K. Kumada H. Risk factors of hepatitis C virus-related liver cirrhosis in young adults: positive family history of liver disease and transporter associated with antigen processing 2(TAP2)*0201 Allele. Journal of Medical Virology. 64(2):109-16, 2001 Jun.

Abstract

The aim of this study was to clinically characterize young patients with hepatitis-C-related cirrhosis. We compared 27 patients with liver cirrhosis (Group LC) who were anti-HCV positive, aged 40 years or less at the time of diagnosis, with 323 consecutive patients with HCV-related chronic hepatitis (Group CH) matched for age and gender. Furthermore, Group LC was divided into two arbitrary groups (29-35 years, n = 8 /36-40 years, n = 19), based on the age of patients at the time of diagnosis of liver cirrhosis. Patients' characteristics and family history were investigated, and the frequency of transporter associated with antigen processing 2 (TAP2) was determined. A family history of liver disease was present in 40.7% of Group LC but in 18.0% of Group CH (P < 0.05). The younger the age of diagnosis of cirrhosis in Group LC, the higher the frequency of a positive family history (29-35 years, 87.5%; 36-40 years, 21.1%, P < 0.05). The frequency of TAP2*0201 was significantly higher in young adult patients with HCV-related liver cirrhosis than in HCV carriers with normal ALT (P < 0.05), and tended to be higher than in uninfected normal subjects (P = 0.05). The cumulative survival rate of cirrhosis patients with family history of liver diseases was significantly lower than that of cirrhosis patients without such history (P < 0.05). Our findings suggest that a positive family history of liver disease and TAP2*0201 polymorphism may be risk factors for HCV-related liver cirrhosis in young adults. Copyright 2001 Wiley-Liss, Inc.

3260. Al-Sheyyab M. Batieha A. El-Khateeb M. The prevalence of hepatitis B, hepatitis C and human immune deficiency virus markers in multi-transfused patients. Journal of Tropical Pediatrics. 47(4):239-42, 2001 Aug.

Abstract

All patients presenting with hereditary hemolytic anemia, (n = 143) over a period of 18 months were enrolled in a study to evaluate the prevalence of hepatitis B, hepatitis C and HIV in multi-transfused patients in Jordan, and to identify possible related risk factors. All patients were treated in the Thalassemia Unit at Princess Rahma Teaching Hospital. Relevant clinical data were collected. Blood specimens were taken from these patients and tested for HbsAg, HbsAb, hepatitis core IgMAb, hepatitis core IgGAb, HCVAb, and ELISA for HIV. Fifty-eight (40.5 per cent) of the specimens were HCVAb positive, while only five (3.5 per cent) of them were positive for HBsAg. None of the specimens were positive for HIV. The frequency of blood transfusion and the time of diagnosis before or after 1995, were investigated as possible risk factors for viral seropositivity. Only the time of diagnosis was a statistically significant risk factor for HCVAb positivity (OR = 4.49; p = 0.005). In conclusion, hepatitis C acquisition is a serious risk for multi-transfused patients in Jordan. Hepatitis B is relatively less common. Blood screening initiated after 1995 in Jordan has significantly reduced the risk of hepatitis C associated with blood transfusion.

3261. Andries S. Casamayou L. Sempoux C. Burlet M. Reding R. Bernard Otte J. Buts JP. Sokal E. Posttransplant immune hepatitis in pediatric liver transplant recipients: incidence and maintenance therapy with azathioprine. Transplantation. 72(2):267-72, 2001 Jul 27.

Abstract

BACKGROUND: Cases of so-called autoimmune hepatitis (AH) have been reported after liver transplantation. Our aim was to evaluate the incidence in a series of 471 pediatric liver transplant recipients. METHODS: Between 1984 and 1998, 471 children had orthotopic liver transplantation (OLT). Children are followed up on a regular basis, with full clinical, biochemical, and histologic evaluation at 6 months, 1, 2, 5, 7, and 10 years after OLT. Children with unexplained abnormal liver tests were screened for autoimmune markers (total gamma-globulins, smooth muscle antibodies [SMA], liver kidney microsome antibodies [LKM], antinuclear factor [ANA]). From January of 1998 until December of 1998, autoimmune markers were prospectively searched in all children admitted for regular posttransplant follow-up (n = 118). RESULTS: Eleven of 471 children (2.35%) were found with autoimmune hepatitis, 9 retrospectively and 2 prospectively. None had previous autoimmune liver disease. Patients had a history of steroid-dependent hepatitis. Histology showed variable degree of portal and lobular inflammation, piecemeal necrosis, and bridging collapse. Mean (+/-SDS) aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities at diagnosis were 173+/-145 and 196+/-157 IU/L, respectively (nl<32). Median gamma-globulin levels reached 1365 mg/dl versus 931 mg/dl in controls (P<0.05). Nine had ANA (titer 1/80 up to 1/10,000), 1 SMA (1/320), and 2 LKM1 antibodies (1/1280). Patients did not respond to increasing charge of cyclosporine (n=10) or tacrolimus (n=1). Eleven received steroids (prednisolone: 2 mg/kg per day, then tapered) and azathioprine (1.5 to 2.5 mg/kg per day). All patients normalized within 3 months (mean AST/ALT levels of 26+/-8 and 30+/-9 IU/L). Three had mild to moderate relapse with increase of ALT thereafter. Gamma-globulins decreased to 1190 mg/dl (ns). Amongst the 116 remaining prospectively evaluated patients, 85 had normal evaluation, despite low titers of autoantibodies in 15 (SMA< or =1/40, ANA 1/80). Thirty-one patients had graft dysfunction, related to well-explained posttransplant causes, among which 7 had similar low levels of autoantibodies. CONCLUSIONS: A total of 2.35% of our transplant children present evidence of immune hepatitis after transplantation. Patients do not respond to increasing cyclosporine or tacrolimus levels and require steroid and azathioprine. In view of this specific treatment, systematic screening for "autoimmune" markers is advised in children with liver transplant.

3262. Andriulli A. Festa V. Leandro G. Rizzetto M. Usefulness of a liver biopsy in the evaluation of patients with elevated ALT values and serological markers of hepatitis viral infection: an AIGO study. Digestive Diseases & Sciences. 46(7):1409-15, 2001 Jul.

Abstract

Our study objective was to determine the current use of liver biopsy in chronic viral hepatitis and how patient management is affected by the procedure. Members of the Italian Association of Hospital Gastroenterologists were asked to complete a questionnaire for patients submitted to biopsy. Their clinical diagnosis was compared with the histological diagnosis. Of 660 patients evaluated, we selected 535 cases with viral infection. Concordance of clinical vs histologic diagnosis amounted to 84.3%, with 92.7% sensitivity and 32.4% specificity rates for diagnosing chronic hepatitis; the clinical diagnosis was correct in only 24 of 57 cases with cirrhosis. In 20 cases (3.7%) additional diagnoses were provided. The biopsy was rated avoidable in 36.8% of cases. Knowledge about grading and staging was considered of value in 59.6 and 66.4% of cases, respectively; however, when it became available, the scheduled treatment with interferon was not changed in 81.7 and 80.9% of cases. In the majority of patients with abnormal ALT and infection with HCV and/or HBV, histology documents mild/moderate inflammation with minimal fibrosis and liver biopsy neither increases the accuracy of clinical diagnosis nor affects the choice of therapy. The data from this study support the view that liver biopsies are less helpful than conventionally understood.

3263. Aoyagi K. Iida K. Ohue C. Matsunaga Y. Tanaka E. Kiyosawa K. Yagi S. Performance of a conventional enzyme immunoassay for hepatitis C virus core antigen in the early phases of hepatitis C infection. Clinica y Laboratorio. 47(3-4):119-27, 2001.

Abstract

There are periods within the early phase of hepatitis C virus (HCV) infection in which the anti-HCV antibody test is unable to confirm HCV viremia. To reduce the risk of transmitting HCV through transfusions, we developed a simple and highly sensitive enzyme immunoassay (EIA) which detects the core antigen of HCV (HCVcAg). This assay employed a conventional colorimetric EIA system, and was based on a two-step sandwich assay, using a 96- well microplate. The reproducibility of the results was very high. When the cutoff values were set to 30 fmol of recombinant HCVcAg/L, as determined by the distribution of healthy subject sera (n=223), 99.6% of healthy subject sera and 100% of hepatitis B patient sera (n=50) were negative for HCVcAg. The clinical performance of this EIA was examined using 14 commercially available seroconversion panels. In every panel, HCVcAg could be detected at points preceding the seroconversion of anti-HCV antibodies. The points at which HCVcAg was detected were the same as those at which it was detected by an AMPLICOR HCV Monitor test. The EIA's window period for detecting the HCVcAg in all panels was on average 26 days shorter than that of the anti-HCV antibody test. In three panels where the first sample is negative for HCV RNA, the window period was shortened 50 days by this EIA for HCVcAg. There was a positive correlation between the concentration of HCVcAg and HCV RNA in anti-HCV antibody negative specimens. This assay was simpler to perform than assays based on gene amplification technology for the detection of HCV RNA, and the window period was shortened to that of the AMPLICOR HCV Monitor test. Thus, the EIA for HCVcAg would be useful in screening seroconverting donors and could reduce the residual risk of secondary HCV infections through transfusions.

3264. Arens M. Clinically relevant sequence-based genotyping of HBV, HCV, CMV, and HIV. [Review] [62 refs] Journal of Clinical Virology. 22(1):11-29, 2001 Aug.

Abstract

The term 'genotyping' describes the genetic characterization of a genome. The genotype analysis is performed to identify mutations that differentiate one individual or strain from another. The mutations may confer resistance to specific antiviral drugs or they may simply allow classification of a strain as to 'type' and 'subtype'. There are four human viruses for which genotype information is clinically useful. Hepatitis B virus (HBV) infections are being treated with antiretroviral drugs and resistance after prolonged treatment is common. Since HBV cannot be cultured, the only method of detecting resistance-conferring mutations in the genome is a genotypic analysis. Hepatitis C virus (HCV) infection can be cured by treatment with the combination of interferon and ribavirin but certain strains of virus are more resistant to treatment than others. The current recommendations are that all HCV type 1 infections be treated for 12 months whereas other types may be successfully treated in 6 months. Since interferon treatment may have significant side effects, the determination of HCV genotype is an important aspect of this therapeutic regimen. Treatment of cytomegalovirus (CMV) disease with nucleoside analogues occasionally results in resistant virus with mutations in the phosphotransferase gene (UL97) and/or the DNA polymerase gene (UL54) that can be tested with phenotypic or genotypic assays. Since CMV grows very slowly, it may be more clinically useful to perform a rapid genotypic assay although only the UL97 gene can be efficiently genotyped. Finally, the virus for which genotyping has become the standard of care, human immunodeficiency virus type 1 (HIV-1) can now be genotyped routinely by many clinical virology labs experienced with molecular amplification methods and automated DNA sequencing technology. All currently-available antiretroviral drugs are directed against either the protease or reverse transcriptase genes of HIV-1 and the mutations within these genes that confer resistance have been well described. Sequence-based genotyping methods are not necessarily the best approach for routine genotyping of these four viruses, but sequencing is the gold standard from which other methods are developed and against which they are compared. [References: 62]

3265. Badur S. Akgun A. Diagnosis of hepatitis B infections and monitoring of treatment. [Review] [33 refs] Journal of Clinical Virology. 21(3):229-37, 2001 Jun.

Abstract

Worldside viral hepatitis is still recognized as a major problem particularly in developing countries. During the past two decades there has been important progress in the field of viral hepatitis; the adaptation of molecular biology techniques to viral hepatitis has proven to be of great utility in the diagnosis of 'classical' hepatitis viruses, in monitoring during treatment, and also in learning more about the 'new' viruses. Here, the progress and pitfalls of serologic and molecular diagnosis techniques for viral hepatitis, unusual profiles and benefits of quantitative DNA/RNA tests will be discussed. [References: 33]

3266. Barrett S. Goh J. Coughlan B. Ryan E. Stewart S. Cockram A. O'Keane JC. Crowe J. The natural course of hepatitis C virus infection after 22 years in a unique homogenous cohort: spontaneous viral clearance and chronic HCV infection. Gut. 49(3):423-30, 2001 Sep

Abstract

BACKGROUND/AIMS: The cohort of Irish women infected with hepatitis C virus (HCV) genotype 1b via contaminated anti-D immunoglobulin in 1977 represent a unique homogenous group to investigate the natural course of HCV infection. METHODS: The clinical status of 87 polymerase chain reaction (PCR) positive and 68 PCR negative women was investigated at diagnosis (1994/95) and after 4-5 years of follow up (21/22 years after inoculation). Other features investigated included: histological status/progression, psychosocial impact of HCV infection, extrahepatic manifestations, and HLA class II associations. RESULTS: The most common symptoms reported were fatigue and arthralgia. Furthermore, 77% of women fell within the clinical range for psychological distress. A history of icteric hepatitis was reported in 20.6% of PCR negative and 3.4% of PCR positive women after inoculation (p=0.002). The mean histological activity index/fibrosis scores of PCR positive and negative women were 4.1 (1.4)/1.1 (1.3) and 2.1 (1.5)/0.15 (0.36) at diagnosis and 4.1 (1.2)/1.0 (1.0) in 44 PCR positive women after five years of follow up. Cirrhosis or hepatocellular carcinoma was not observed. The DRB1*01 allele was present in 28.8% of PCR negative and 8.7% of PCR positive women (p=0.004). The prevalence rates of mixed cryoglobulinaemia, sicca complex, positive thyroid autoantibodies, antinuclear antibody, rheumatoid factor, and antimitochondrial antibody in PCR positive women were 12.7%, 7.6%, 13.9%, 5.1%, 3.8%, and 3.8%. CONCLUSIONS: A benign course of HCV infection with lack of disease progression was observed in women with chronic HCV, 22 years after inoculation. Acute icteric hepatitis and the HLA DRB1*01 allele were associated with viral clearance. Despite this favourable outcome, high levels of psychological distress and poor quality of life were present.

3267. No Abstract

3268. Cantaloube JF. Gallian P. Attoui H. Biagini P. De Micco P. De Lamballerie X. Erroneous HCV genotype assignment by a hybridization typing assay in a case of posttransfusion HCV infection. Transfusion. 41(3):429-30, 2001 Mar.

3269. Cashman TM. Elm JL Jr. Wu M. Tom T. Effler PV. Hepatitis C, diagnosis and management: a survey of practicing physicians in Hawaii. Hawaii Medical Journal. 60(6):148-54, 2001 Jun.

Abstract

We surveyed 652 Hawaii physicians who diagnosed hepatitis C (HCV) since 1997. Less than 20% of licensed physicians have diagnosed HCV and initial estimates suggest there are 12,000 to 18,000 undiagnosed HCV cases in Hawaii. Treatment is concentrated among twelve physicians and aggressive case finding may overwhelm present resources. More primary care physicians need to participate in the detection and management of HCV.

3270. No Abstract

3271. No Abstract

3272. Cho JW. Baek WK. Suh SI. Yang SH. Chang J. Sung YC. Suh MH. Hepatitis C virus core protein promotes cell proliferation through the upregulation of cyclin E expression levels. Liver. 21(2):137-42, 2001 Apr.

Abstract

AIMS/BACKGROUND: The hepatitis C virus (HCV) core protein is known to play an important role in hepatocarcinogenesis. Recent studies have suggested that the increased proliferation rate of hepatocytes is a major risk factor for the development of hepatocellular carcinoma. In this study, we investigated whether the HCV core protein promotes the cell growth rate through the modulation of cyclin E expression levels. METHODS/RESULTS: HCV core stable transfectant Rat-1 cell lines showed a markedly increased proliferation rate compared to mock cells. Cyclin E expression and its associated kinase activities were remarkably increased in HCV core stable transfectants. Cyclin E mRNA levels were also upregulated in these cell lines. CONCLUSIONS: Our data suggest that the HCV core protein promotes cell proliferation through upregulation of the cyclin E expression levels, implying this property of HCV core protein plays an important role in hepatocarcinogenesis.

3273. Chu CW. Hwang SJ. Luo JC. Lai CR. Tsay SH. Li CP. Wu JC. Chang FY. Lee SD. Clinical, virologic, and pathologic significance of elevated serum alpha-fetoprotein levels in patients with chronic hepatitis C. Journal of Clinical Gastroenterology. 32(3):240-4, 2001 Mar.

Abstract

Elevated serum alpha-fetoprotein (AFP) in patients with chronic hepatitis C is not uncommonly seen, but the pathogenesis of this phenomenon remains unclear. The aims of this study were to assess the prevalence of elevated serum AFP in patients with chronic hepatitis C and to evaluate the clinical, virologic, and histopathologic significance of this phenomenon. One hundred and fifteen Chinese patients with a histologic diagnosis of chronic hepatitis C were enrolled. None had evidence of hepatocellular carcinoma by image study at enrollment and for at least 2 years' follow-up. Of the 115 patients, 33 (29%) had elevated serum AFP (more than 12 ng/mL). There was a significantly lower mean serum albumin (4.0 +/- 0.1 vs. 4.3 +/- 0.1 gm/dL, p <0.001) and higher mean scores for periportal necroinflammation (3.3 +/- 0.3 vs. 2.3 +/- 0.2, p = 0.007) and fibrosis (2.3 +/- 0.2 vs. 1.1 +/- 0.1, p < 0.001) in patients with elevated serum AFP when compared with patients without elevated serum AFP. Patients with elevated serum AFP had significantly more incidences of genotype 1b infection when compared with patients without elevated serum AFP (77% vs. 51%, p = 0.021). Mean serum hepatitis C virus (HCV) RNA titer showed no significant difference between the two groups. Multivariate logistic regression analysis showed that as serum albumin of less than 4.2 gm/dL, a histology fibrotic score of more than 3, and HCV genotype 1b infection were significantly independent predictors associated with elevated serum AFP. In conclusion, elevated serum AFP levels were significantly correlated with lower serum albumin levels, advanced fibrosis/cirrhosis, and genotype 1b infection in patients with chronic hepatitis C.

3274. Du B. You S. Present situation in preventing and treating liver fibrosis with TCM drugs. [Review] [26 refs] Journal of Traditional Chinese Medicine. 21(2):147-52, 2001 Jun.

Abstract

Considerable evidences have shown that the mechanism of TCM drugs for preventing and treating liver fibrosis is very complicated. TCM treatment can not only inhibit viral replication, ameliorate inflammation and promote blood circulation in the liver, and enhance regeneration of the hepatic cells, but also inhibit HSC proliferation, intra- and extracellular secretion, decrease the secretion of collagen and promote its degradation and re-absorption. However, most of the animal models are only suitable for studies of acute hepatitis. Establishment of cell lines suitable for studies of fibrosis is still at its initial stage. What we expect is that comprehensive clinical studies in TCM treatment of liver fibrosis will be carried out and evaluation of each datum given, both of which are of importance. [References: 26]

3275. Erensoy S. Diagnosis of hepatitis C virus (HCV) infection and laboratory monitoring of its therapy. [Review] [45 refs] Journal of Clinical Virology. 21(3):271-81, 2001 Jun.

Abstract

BACKGROUND: Just after the identification and characterization of hepatitis C virus (HCV) in 1989, tests for the detection of HCV antibodies or HCV RNA in serum were developed. The enzyme-linked immunosorbent assays (ELISAs) and confirmatory/supplemental analytical antibody tests were improved in sensitivity and specificity with the development of further generations of these assays. Application of molecular tests for detecting, quantifying, and characterization of the infecting virus became very important in management of HCV infection. OBJECTIVE AND DESIGN: This review summarizes the assays developed for the diagnosis and management of HCV infection. Strategies for the diagnosis and monitoring with the advantages and disadvantages of the assays based on the setting and goal are discussed according to data in the literature and our experience. Results: Specific laboratory diagnostic tests for hepatitis C virus infection may be discussed under two titles: (i) Serological antibody tests which detect anti-HCV in serum or plasma; (ii) Molecular tests which detect HCV RNA genome, investigate viral load, and determine the characteristics of the genome. Strategies in different laboratory settings which screen populations with different HCV prevalences vary. CONCLUSIONS: Anti-HCV positive result in a low-risk setting such as blood banks should be confirmed with an analytical antibody test. Then a HCV RNA test should be performed on serum of the person with a positive or indeterminate confirmatory test result. On the contrary, anti-HCV positive test result in high-risk population or a situation where HCV infection is suspected, it is likely to be true positive and confirmation with HCV RNA test will be significant. Quantitative HCV RNA test and genotyping should be performed if therapy is considered. [References: 45]

3276. Fabrizi F. Martin P. Dixit V. Quan S. Brezina M. Kaufman E. Sra K. Mousa M. DiNello R. Polito A. Gitnick G. Automated RIBA HCV strip immunoblot assay: a novel tool for the diagnosis of hepatitis C virus infection in hemodialysis patients. American Journal of Nephrology. 21(2):104-11, 2001 Mar-Apr.

Abstract

Hemodialysis (HD) patients remain a high-risk group for hepatitis C virus (HCV) infection. Serological assays (enzyme-linked immunosorbent assays, ELISAs) are the only tests currently approved by the Food and Drug Administration in the United States for the diagnosis of HCV. The RIBA HCV Strip Immunoblot Assay (SIA) is an established method for supplemental testing of repeat reactive hepatitis C ELISA patients on HD. However, the current manual procedure is labor intensive, requiring subjective band scoring and result interpretation. Recently, the automated CHIRON RIBA HCV Processor System has been designed to perform RIBA supplemental testing. The CHIRON RIBA HCV Processor System consists of a bench-top instrument that provides objective evaluation of the RIBA immunoblot strips, by measuring the light differentially reflected from the developed bands and white background, creating a density of reflectance. The CHIRON RIBA HCV Processor System assesses the intensity of each of the reactive bands in relation to the intensity of the internal control bands on each RIBA HCV strip. Comparison between processor and manual protocols was performed using a large (n = 200) cohort of ELISA 3.0 HCV negative and positive patients on maintenance HD. The test characteristics of RIBA HCV 3.0 SIA were identical with manual and automated runs. The relative intensity values of antigenic bands by the CHIRON RIBA HCV 3.0 Processor System between anti-HCV positive and negative patients were significantly different; only 15 of 784 (1.9%) antigenic bands had borderline reactivities. The correlation of test results between manual and automated runs was very high (kappa value 0.989). Among positive results by RIBA HCV 3.0 SIA, there was a strong concordance between manual and automated runs with regard to the pattern of reactivity (kappa value 0.943). The discordant results between manual and automated protocols were attributable to increased variability of antigen scores close to the cutoff value for both tests. In conclusion, the CHIRON RIBA HCV 3.0 Processor System is capable of performing RIBA HCV 3.0 SIA in the HD population accurately with minimal operator involvement. The test characteristics of RIBA HCV 3.0 SIA were identical by manual and automated runs. There was a strong correlation between the results of the manual and automated runs; the few discordant results between the two procedures were mostly due to increased variability of antigen scores close to the cutoff value for both tests. The Centers for Disease Control and Prevention in the USA have recently included chronic HD patients among those persons for whom routine HCV testing is recommended; HCV-infected patients on HD often have a high rate of indeterminate results by manual RIBA technology which is operator dependent for band scoring and result interpretation. The CHIRON RIBA HCV 3.0 Processor System may be very useful for supplemental anti-HCV testing of ELISA repeat reactive specimens in clinical practice within dialysis units. Copyright 2001 S. Karger AG, Basel

Abstract

3277. Funato T. Satou N. Abukawa D. Satou J. Abe Y. Ishii KK. Iinuma K. Kaku M. Sasaski T. Quantitative evaluation of cytomegalovirus DNA in infantile hepatitis. Journal of Viral Hepatitis. 8(3):217-22, 2001 May.

Abstract

We used a PCR method to develop a diagnostic assay for the detection of cytomegalovirus (CMV) DNA in infantile hepatitis, which has been suggested to be associated with CMV infection. CMV DNA was detected in 25 (58.1%) of 43 patients with elevated serum alanine aminotransferase (ALT) levels but no jaundice, and no hepatitis B or C as assessed by conventional PCR. None of the samples from 97 healthy infants tested positive for CMV DNA. We assayed CMV DNA quantitatively in blood using a real-time PCR system that allowed reproducible detection of at least 10 copies of CMV DNA. When 1 microg of DNA from each blood sample was used in this system, a good correlation was obtained between the calculated and measured copy numbers of CMV DNA. This system detected CMV DNA in 29 patients (67.4%) with liver dysfunction. Serial studies in patients with liver dysfunction revealed that CMV DNA copy number decreased, ultimately to below 10, as the ALT levels normalized. In contrast, no CMV DNA copies were detectable by the real-time system in any of the samples from control subjects. These results highlight the usefulness of detecting CMV DNA in the diagnosis of infantile hepatitis and indicate that the real-time quantitative PCR assay may be a valuable tool for monitoring CMV-associated infantile hepatitis.

3278. Gopalani A. Ahuja TS. Prevalence of glomerulopathies in autopsies of patients infected with the hepatitis C virus. American Journal of the Medical Sciences. 322(2):57-60, 2001 Aug.

Abstract

BACKGROUND: Several reports have shown hepatitis C virus (HCV) infection to be associated with various extrahepatic manifestations, including certain forms of glomerulopathy. The most frequently reported glomerulonephritis in patients infected with HCV is either membranoproliferative glomerulonephritis (MPGN) or cryoglobulinemic glomerulonephritis, and HCV has been directly implicated in their pathogenesis. Other investigators have reported a higher prevalence of HCV infection in patients with membranous glomerulonephritis, IgA nephropathy, and focal segmental glomerulosclerosis (FSGS). However, the prevalence of these glomerulopathies in patients infected with HCV is unknown. METHODS: We conducted a 5-year retrospective review to determine prevalence of glomerulopathies in autopsies of patients infected with HCV. The renal histology on the autopsy reports was carefully reviewed for appropriate diagnosis of glomerulonephritis. RESULTS: Of the 114 autopsies of patients infected with HCV during this period, the majority had been incarcerated and had state-mandated autopsies. The mean age of the patients was 46.8 +/- 10 years (+/- SD; range, 19-87). Of the 114 patients, 46 were white, 37 were African American, and 31 were Hispanic. The glomerulopathies seen were 3 MPGN, 2 membranous, 3 HIV-associated nephropathy, 1 idiopathic FSGS, 1 minimal change glomerulonephritis, and 3 diabetic nephropathy. CONCLUSION: We conclude that although HCV is reported to be associated with membranoproliferative and membranous glomerulonephritis, their prevalence in these patients is not common.

3279. Hahn JA. Page-Shafer K. Lum PJ. Ochoa K. Moss AR. Hepatitis C virus infection and needle exchange use among young injection drug users in San Francisco. Hepatology. 34(1):180-7, 2001 Jul.

Abstract

Young injection drug users (IDUs) in San Francisco may be at high risk for hepatitis C virus (HCV) infection despite access to several needle exchange venues. The authors conducted a cross-sectional study from 1997 to 1999 in San Francisco to estimate the prevalence and incidence of antibody to HCV (anti-HCV) among street-recruited IDUs under age 30, and to examine risk behaviors and sources of sterile needles. Among 308 participants, the prevalence of anti-HCV was 45%. Using statistical modeling, incidence of HCV infection was estimated to be 11 per 100 person years. Independent risk factors for anti-HCV included age (odds ratio [OR], 1.17 per year; 95% confidence interval [CI], 1.05-1.30), years injecting (OR, 1.21 per year; 95% CI, 1.10-1.34), years in San Francisco (OR, 1.06 per year; 95% CI, 1.00-1.14), first injected by a sex partner (OR, 4.06; 95% CI, 1.74-9.52), injected daily (OR, 3.85; 95% CI, 2.07-7.17), ever borrowed a needle (OR, 2.56; 95% CI, 1.18-5.53), bleached last time a needle was borrowed (OR, 0.50; 95% CI, 0.24-1.02), snorted or smoked drugs in the prior year (OR, 0.48; 95% CI, 0.26-0.89), and injected by someone else in the prior month (OR, 0.50; 95% CI, 0.25-0.99). In the prior month, 88% used at least 1 of several needle exchange venues, and 32% borrowed a needle. We conclude that anti-HCV prevalence is lower than in previous studies of older IDUs, but 11% incidence implies high risk of HCV infection in a long injecting career. Despite access to sterile needles, borrowing of needles persisted.

3280. Halfon P. Trimoulet P. Bourliere M. Khiri H. de Ledinghen V. Couzigou P. Feryn JM. Alcaraz P. Renou C. Fleury HJ. Ouzan D. Hepatitis C virus genotyping based on 5' noncoding sequence analysis (Trugene). Journal of Clinical Microbiology. 39(5):1771-3, 2001 May.

Abstract

Hepatitis C virus (HCV) genotyping of samples from 184 patients with chronic HCV infection by the Trugene 5'NC genotyping kit, based on sequence analysis of the 5' noncoding region (5' NCR), and the InnoLiPA assay was evaluated. In addition to these methods, the 184 samples were also analyzed by sequencing of part of the NS5B of the HCV genome after in-house PCR amplification, as a means of validating results obtained with the 5' NCR. The distribution of the genotypes typed by NS5B sequence analysis was as follows: 1a, 41 samples; 1b, 58 samples; 1d, 1 sample; 2a, 5 samples; 2b, 2 samples; 2c, 7 samples; 3a, 46 samples; 4a, 7 samples; 4c, 1 samples; 4e, 9 samples; 5a, 6 samples; 6a, 1 sample. The Trugene and InnoLiPA assays gave concordant results within HCV types in 100% of cases. The ability to discriminate at the subtype level was 76 and 74% for the Trugene and the InnoLiPA assays, respectively.

3281. Hitzler WE. Runkel S. Routine HCV PCR screening of blood donations to identify early HCV infection in blood donors lacking antibodies to HCV. Transfusion. 41(3):333-7, 2001 Mar.

Abstract

BACKGROUND: Detection of early hepatitis C infection of blood donors is still a major problem for blood transfusion. Common anti-HCV screening assays show differences in sensitivity and specificity. The often mild symptoms of acute hepatitis C also cause difficulties in the identification of early HCV infection. The feasibility and efficacy of routine screening of blood donations for HCV RNA were investigated. STUDY DESIGN AND METHODS: Blood donations (n = 251,737) were screened for HCV RNA over 4 years. RNA extraction, amplification, and detection were done by two commercial HCV PCR kits (HCV Cobas Amplicor and HCV Cobas Amplicor 2.0, Roche Diagnostics). Screening was done by pool testing with a maximum pool size of 40 serum samples. RESULTS: Three donations out of 251,737 were HCV RNA positive and anti-HCV negative. ALT levels of these donations were 271, 32, and 10 U per L. The HCV infection of a fourth HCV RNA-positive donor could not be identified by routine, second-generation HCV EIA (Abbott Diagnostika). In this case, two previous donations were also HCV RNA positive, and three second-generation test systems (Abbott) could not detect anti-HCV, whereas third-generation anti-HCV screening assays detected antibody with different sensitivity. The first HCV RNA-positive donation was identified only by the HCV ELISA 3.0 (Ortho Diagnostic Systems). The results of confirmatory assays like RIBA HCV 3.0 (Ortho) and Matrix (Abbott) indicate a restricted immune response to NS3 only. CONCLUSION: HCV RNA detection by PCR can be carried out routinely in blood donor screening without significant delay of release of the components. The residual risk of transmission can be reduced by identification of early infection, which can lead to an improved safety of blood components. RNA screening can also be advantageous in cases of incomplete or lack of antibody response to HCV.

3282. No Abstract

3283. No Abstract

3284. Koff RS. Risks associated with hepatitis A and hepatitis B in patients with hepatitis C. [Review] [36 refs] Journal of Clinical Gastroenterology. 33(1):20-6, 2001 Jul.

Abstract

Individuals with hepatitis C virus (HCV) are at risk for acquiring hepatitis A virus (HAV) or hepatitis B virus (HBV) because of shared risk factors. A number of organizations recommend vaccination against HAV and HBV for patients with HCV. The rationale for vaccinating these patients is to prevent hepatic superinfections. Acute HAV superinfection causes more severe disease, acute hepatic failure, and higher fatality rates in patients with underlying chronic liver disease, specifically chronic HBV infection and chronic HCV infection. Available data, although limited, suggest that HBV coinfection with HAV and HCV causes more severe hepatic injury than infection with HAV or HCV alone. At standard doses, hepatitis A and hepatitis B vaccines are safe and immunogenic in patients with mild-to-moderate hepatitis C or chronic liver disease. Regardless of disease severity, vaccination should be routinely administered to patients upon diagnosis of HCV infection. Early vaccination is important because response to vaccination is reduced as liver disease progresses. Prevaccination and postvaccination serology testing is recommended in specific populations. A new combination hepatitis A and hepatitis B vaccine has been shown to be as safe and effective as monovalent hepatitis A and B vaccines and is currently under review by the United States Food and Drug Administration. A combination vaccine would offer ease of administration and convenience and could increase compliance in patients with hepatitis C or other chronic liver disease: two groups that should be more aggressively targeted by healthcare professionals. [References: 36]

3285. Kozlowski A. Charles SA. Harris JM. Development of pegylated interferons for the treatment of chronic hepatitis C. [Review] [46 refs] Biodrugs. 15(7):419-29, 2001.

Abstract

The chemical attachment of poly(ethylene glycol) [PEG] to therapeutic proteins produces several benefits, including enhanced plasma half-life, lower toxicity, and increased drug stability and solubility. In certain instances, pegylation of a protein can increase its therapeutic efficacy by reducing the ability of the immune system to detect and mount an attack on the compound. A PEG-protein conjugate is formed by first activating the PEG moiety so that it will react with, and couple to, the protein. PEG moieties vary considerably in molecular weight and conformation, with the early moieties (monofunctional PEGs; mPEGs) being linear with molecular weights of 12kD or less, and later moieties being of increased molecular weights. PEG2, a recent innovation in PEG technology, involves the coupling of a 30kD (or less) mPEG to lysine that is further reacted to form a branched structure that behaves like a linear mPEG of much larger molecular weight. These compounds are pH and temperature stable, and this factor along with the large molecular weight may account for the restricted volume of distribution seen with drugs utilising these reagents. Three PEG-protein conjugates are currently approved for clinical use in the US, with more under clinical development. Pegademase is used in the treatment of severe combined immunodeficiency disease, pegaspargase for the treatment of various leukaemias, and pegylated interferon-alpha for chronic hepatitis C virus infections. As illustrated in the case of the 2 pegylated interferon-alphas, all pegylated proteins are not equal. The choice of PEG reagent and coupling chemistry is critical to the properties of the PEG-protein conjugate, with the molecular weight of the moiety affecting its rate and route of clearance from the body, and coupling chemistry affecting the strength of the covalent attachment of PEG to therapeutic protein. [References: 46]

3286. Levis J. Kenny-Walsh E. O'Sullivan K. Horgan M. Whelton M. Shanahan F. Fanning L. Strategy for the maximization of clinically relevant information from hepatitis C virus, RT-PCR quantification. Journal of Clinical Virology. 20(3):163-71, 2001 Feb.

Abstract

BACKGROUND: The increasing clinical application of viral load assays for monitoring viral infections has been an incentive for the development of standardized tests for the hepatitis C virus. OBJECTIVE: To develop a simple model for the prediction of baseline viral load in individuals infected with the hepatitis C virus. METHODOLOGY: Viral load quantification of each patient's first sample was assessed by RT-PCR-ELISA using the Roche MONITOR assay in triplicate. Genotype of the infecting virus was identified by reverse line probe hybridization, using amplicons resulting from the qualitative HCV Roche AMPLICOR assay. RESULTS: Retrospective evaluation of first quantitative values suggested that 82.4% (n=168/204) of individuals had a viral load between 4.3 and 6.7 log(10) viral copies per ml. A few patients (3.4%; n=7/204) have a serum viremia less than the lower limit of the linear range of the RT-PCR assay. Subsequent, prospective evaluation of hepatitis C viral load of all new patients using a model based on the dynamic range of viral load in the retrospective group correctly predicted the dynamic range in 75.9% (n=33/54). CONCLUSION: The dynamic range of hepatitis C viremia extends beyond the linear range of the Roche MONITOR assay. Accurate determination of serum viremia is substantially improved by dilution of specimens prior to quantification.

3287. Lieber CS. Liver diseases by alcohol and hepatitis C: early detection and new insights in pathogenesis lead to improved treatment. [Review] [152 refs] American Journal on Addictions. 10 Suppl:29-50, 2001.

Abstract

Much progress has been made in the understanding of the pathogenesis of alcoholic liver disease, resulting in improvement of treatment. Therapy must include correction of nutritional deficiencies, while taking into account changes of nutritional requirements. Methionine is normally activated to S-adenosylmethionine (SAMe). However, in liver disease, the corresponding enzyme is depressed. The resulting deficiencies can be attenuated by the administration of SAMe but not by methionine. Similarly, phosphatidylethanolamine methyltransferase activity is depressed, but the lacking phosphatidylcholine (PC) can be administrated as polyenylphosphatidylcholine (PPC). Chronic ethanol consumption increases CYP2E1, resulting in increased generation of toxic acetaldehyde and free radicals, tolerance to ethanol and other drugs, and multiple ethanol-drug interactions. Experimentally, PPC opposes CYP2E1 induction and fibrosis. Alcoholism and hepatitis C infection commonly co-exist, with acceleration of fibrosis, cirrhosis, and hepatocellular carcinoma. PPC is being tested clinically as a corresponding antifibrotic agent. Available antiviral agents are contraindicated in the alcoholic. Anti-inflammatory agents, such as steroids, may be selectively useful. Finally, anticraving agents, such as naltrexone or acamprosate, should be part of therapy. [References: 152]

3288. No Abstract

3289. No Abstract

3290. Polywka S. Schroter M. Feucht HH. Zollner B. Laufs R. Relevance of reactivity in commercially available hepatitis C virus antibody assays. Journal of Clinical Microbiology. 39(4):1665-8, 2001 Apr.

Abstract

Sera from 2,148 patients were tested with a third-generation microparticle enzyme immunoassay (MEIA), a confirmatory assay, and a reverse transcription-PCR. Overall, 85.6% of reactivities were confirmed, 13.2% were shown to be unspecifically reactive, and 1.2% were indeterminate. The rate of confirmed MEIA reactivities clearly depended on the strength of the reactivity.

3291. No Abstract

3292. Rostaing L. Borde JS. Hasle C. Bories P. Allal A. Abbal M. Durand D. Lack of effect of chronic hepatitis C virus infection on T-cell cytokine production in chronic hemodialysis patients. American Journal of Nephrology. 21(3):194-9, 2001 May-Jun.

Abstract

It has been shown that chronic hemodialysis modifies, to some extent, the normal immune response by both T and B lymphocytes elicited by antigenic stimulation, e.g. by impairing the T-cell-dependent response after vaccination. A new technique, i.e. flow cytometry, enables to assess intracytoplasmically, at the single cell level, the production of a given cytokine. By using it, we studied in healthy volunteers (HV) and in chronic hemodialysis (CHD) patients, with respect to their hepatitis C virus (HCV) status, the production by the T lymphocytes of type 1, and type 2 cytokines. We studied the following cytokines (CK): IL-2, IL-4, IL-5, IL-6, IL-10, IFN-gamma and TNF-alpha in the T-cell lymphocytes (whole, CD4+ and CD8+). There were 13 HV and 59 CHD patients (36 HCV(-) and 23 HCV(+)). Amongst the latter, there were 32 men and 27 women, aged 59.5 +/- 2 years, undergoing CHD since 70 +/- 9.4 months. We found that: (1) the total number of lymphocytes as well as those expressing CD3, CD4, or CD19 were significantly decreased in CHD patients as compared to those from HV; (2) the total number of lymphocytes as well as their different subsets were similar in HCV(+) and in HCV(-) CHD patients; (3) the frequency of T-cell-expressing IL-5 or IL-10 was always low (<1%) in both HV and CHD groups; (4) overall in CHD patients, the mean percentages of T lymphocytes expressing IL-2, IL-4, IFN-gamma or TNF-alpha were respectively 31 +/- 13, 2.5 +/- 1.3, 28 +/- 12 and 34 +/- 11% and were not statistically different between HCV(+) and HCV(-) patients; (5) IL-2 was mainly produced by CD4+ T cells, whereas IFN-gamma was produced by CD8+ T cells, in both HV and CHD groups, and (6) the lymphocytes of CHD patients produced significantly more IL-2 and IL-4 than those from HV, suggesting an activation of their T lymphocytes. We conclude that using the cytokine flow cytometry assay, our study demonstrated that in HCV(+) CHD patients, as opposed to what has been described for HCV(+) patients with normal renal function, there was no impairment in the production of type 1 cytokines by peripheral blood mononuclear cells when compared to HCV(-) CHD patients. Conversely to HV, T lymphocytes from CHD patients are activated. Copyright 2001 S. Karger AG, Basel

3293. Ryan M. Desmond P. Liver toxicity. Could this be a drug reaction?. [Review] [8 refs] Australian Family Physician. 30(5):427-31, 2001 May.

Abstract

BACKGROUND: Adverse reaction to prescription medications, over the counter medications and complementary medicines, are an important cause of liver toxicity. OBJECTIVE: To highlight the importance of drug induced liver toxicity in patients presenting with abnormal liver function tests. DISCUSSION: In patients who present with symptoms of liver dysfunction such as anorexia, itch or Jaundice and in whom liver function tests are abnormal, the possibility of an adverse reaction to medications should be considered. A detailed history of all medications taken in the past few months, including complementary medicines, should be obtained. After exclusion of other causes of liver disease such a viral hepatitis or gallstones, the cessation of the offending medication and the normalisation of liver tests is usually sufficient to establish a diagnosis. Occasionally, referral to a specialist and liver biopsy may be required. [References: 8]

3294. Saab S. Brezina M. Gitnick G. Martin P. Yee HF Jr. Hepatitis C screening strategies in hemodialysis patients. [see comments]. American Journal of Kidney Diseases. 38(1):91-7, 2001 Jul.

Abstract

Hepatitis C virus (HCV) infection is common in patients undergoing chronic hemodialysis, with an estimated yearly incidence of 0.2% and prevalence between 8% and 10%. Although a screening strategy based on alanine aminotransferase (ALT) values is currently recommended, this strategy has not been evaluated for cost-effectiveness compared with other potential screening strategies. A comparison therefore was made using a decision-analysis model of a simulated cohort of 5,000 hemodialysis patients followed up for 5 years. Using direct medical costs, three strategies were evaluated, including: (1) ALT values with confirmatory testing (biochemical), (2) serial enzyme-linked immunosorbent and strip immunoblot assay testing (serological), and (3) polymerase chain reaction (viral). Under baseline assumptions, the per-patient cost of screening hemodialysis patients for HCV was $378 for biochemical-based testing, $195 for serological-based testing, and $696 for viral-based testing. Our model was robust when varying the costs of testing, as well as the incidence and prevalence of HCV infection. Results of sensitivity analysis by varying costs, HCV incidence, and HCV prevalence indicated that serological-based screening was less costly than biochemical testing. Biochemical testing was in turn less costly than viral-based screening. Serological-based testing was also more effective in the diagnosis of de novo HCV infection, with a likelihood ratio of 85, in contrast to the likelihood ratio of 44 with biochemical-based testing using viral-based screening as the gold standard. A serological-based screening strategy is less costly and more effective than biochemical-based screening in the diagnosis of de novo HCV infection. Serological-based screening should be considered for HCV screening in hemodialysis populations.

3295. Sagnelli E. Coppola N. Scolastico C. Mogavero AR. Filippini P. Piccinino F. HCV genotype and "silent" HBV coinfection: two main risk factors for a more severe liver disease. Journal of Medical Virology. 64(3):350-5, 2001 Jul.

Abstract

To evaluate whether HCV genotype and a "silent" HBV infection may be related to a more severe clinical presentation of liver disease, 205 anti-HCV/HCV-RNA positive, HBsAg/anti-HBs negative patients with chronic hepatitis (113 males and 92 females; median age 55 years, range 18-77), were studied on presentation at the Liver Unit from January 1993 to December 1997. Presence of serum anti-HBc, in the absence of HBsAg and anti-HBs, was considered a marker of "silent" HBV infection. Of the 205 patients, 134 had undergone percutaneous liver biopsy. Two main diagnosis groups were established: the mild liver disease group (76 patients), and the severe liver disease group (109 patients); 20 patients who had refused to undergo liver biopsy were not included in the clinical and virological evaluation because the diagnosis was uncertain. The prevalence of severe liver disease was similar in the genotype 1 and non-1 groups (61.3% of 98 patients with genotype 1 and 52.9% of 70 patients with a non-1 genotype). Instead, the 88 patients with "silent" HBV infection showed a higher percentage of severe liver disease than the 97 anti-HBc negative patients (72.7% vs. 46.4%, respectively: P < 0.0005). Of the 88 anti-HBc positive patients, the prevalence of those with severe liver disease was similar in the 32 cases with serum HBV-DNA as detected by PCR and in the 56 HBV-DNA negative (81.2% vs. 67.8%, P = 0.4). The relation between "silent" HBV infection and severe liver disease was observed both in genotype 1 and non-1 infected patients. Nevertheless, the anti-HBc negative patients infected by genotype 1 showed a severe liver disease more frequently than those infected by a non-1 genotype, with a difference that is significant to the statistical analysis (P < 0.05). The findings suggest that "silent" HBV infection in anti-HCV positive chronic hepatitis enhances the severity of the liver disease. Evidence was also found that in patients without "silent" HBV infection there is a correlation between the presence of HCV genotype 1 and the severity of liver disease. Copyright 2001 Wiley-Liss, Inc.

3296. Schroter M. Schafer P. Zollner B. Polywka S. Laufs R. Feucht HH. Strategies for reliable diagnosis of hepatitis C infection: the need for a serological confirmatory assay. Journal of Medical Virology. 64(3):320-4, 2001 Jul.

Abstract

The aim of the study was to examine whether the diagnosis of Hepatitis C (HCV) infection can be obtained reliably without using an immunoblot-based confirmation assay. 1,708 EIA-reactive serum samples were examined retrospectively for (i) optical density value in the screening assay, (ii) reactivity in an immunoblot assay, and (iii) result by RT PCR. In 1,394 (81.0%) samples positive results were obtained by both the HCV EIA and the confirmation assay. OD-values > or = 2.2 were observed in 1026 of these samples, but covered the range from 0.4 to 2.1 in the other 368 samples. The combination of HCV EIA reactivity and indeterminate immunoblot assay was observed in 134 (7.8%) serum samples. HCV RNA was detected in 58 cases by PCR. The OD-values of these 58 samples ranged from 0.4 to >2.2. Especially reactivity against the core recombinant protein was indicative of PCR positivity. The reactivity by the HCV EIA could not be confirmed by immunoblot assay or PCR in 180 (10.5%) sera. These false reactive sera showed OD values by EIA from 0.3 to 2.1. It is concluded that no threshold values can be defined which would allow differentiation between positive, indeterminate, and false reactive result by HCV EIA without producing an unacceptably high number of false negative diagnoses. Not using immunoblot-based confirmation would result in many additional PCR examinations. Therefore, confirmation of reactive HCV EIA results by a serological confirmatory assay must remain an essential part of the diagnostic procedure. Copyright 2001 Wiley-Liss, Inc.

3297. Sheiner PA. Florman SS. Emre S. Fishbein T. Schwartz ME. Miller CM. Boros P. Recurrence of hepatitis C after liver transplantation is associated with increased systemic IL-10 levels. Mediators of Inflammation. 10(1):37-41, 2001 Feb.

Abstract

BACKGROUND: Recurrence of hepatitis C after liver transplantation is an almost universal occurrence. T-cell derived cytokines have an important role in the development of liver damage associated with chronic hepatitis C, their post-transplant levels, however, have not been correlated with histologic recurrence of the disease. AIMS: We sought to analyze levels of TNF-alpha, soluble IL-2 receptor, IL-4 and IL-10 at 1 month, 6 months and 1 year after transplantation in 27 patients undergoing transplantation for hepatitis C related end-stage liver disease. METHODS: HCV RNA levels were monitored by a branched-chain DNA signal amplification assay. Diagnosis of recurrent hepatitis was based on 1-year protocol biopsies and on biopsies performed for liver enzyme elevations. RESULTS: Recurrent hepatitis C was detected in 52% (n=14) of the 27 patients. HCV RNA levels rose over time in all patients regardless of histologic recurrence. TNF-alpha, and IL-4 levels, although elevated, did not show specific patterns over time or in correlation with recurrence. Similarly, the early elevation followed by a gradual decrease over the first year in the amount of soluble IL-2 receptor was not related to histologic recurrence. We observed a significant increase in circulating IL-10 levels over the first year in patients with biopsy-proven recurrence, while patients with no signs of histologic recurrence displayed increased, but steady levels. CONCLUSIONS: These results suggest that while these cytokines are associated with post-transplant recurrence of hepatitis C, their production may be altered by additional factors.

3298. Singh VK. Naik S. Simultaneous amplification of DNA and RNA virus using multiplex PCR system. Clinica Chimica Acta. 308(1-2):179-81, 2001 Jun.

Abstract

A large number of disease-causing bacteria and viruses are being sequenced and PCR is increasingly used for the diagnosis of the diseases. We have designed a multiplex PCR system for hepatitis B virus (HBV), a DNA virus, and hepatitis E virus (HEV), an RNA virus. A modified technique has been standardized for simultaneous extraction of DNA and RNA, followed by a one-step RT-PCR/PCR.

3299. Smythe JS. Anstee DJ. Expression of C antigen in transduced K562 cells. Transfusion. 41(1):24-30, 2001 Jan.

Abstract

BACKGROUND: The Rh blood group system is involved in HDN and transfusion reactions. A retrovirus-expression system was previously used to show that polypeptides carrying the Rh blood group antigens are encoded by the RHD and RHCE genes. This study investigated the structure of the C antigen. STUDY DESIGN AND METHODS: K562 cells were transduced with full-length cDNA encoding Ce and CE antigens, and the expression of C, e, and E antigens was examined by flow cytometry using MoAbs. The importance of Cys16 in C antigen expression was examined by utilizing site-directed mutagenesis to convert Cys16 to Trp in cDNA encoding Ce and CE before expression in K562 cells. RESULTS: When K562 cells were transduced with cDNA that was predicted to encode Ce antigens, clear reactivity with anti-e and anti-C was obtained. In contrast, K562 cells transduced with cDNA that was predicted to encode CE antigens gave strong reactivity with anti-E but failed to react with two examples of anti-C. A third example of anti-C gave weak reactivity. When cDNA encoding Ce antigens was mutated to encode Trp16, one example of anti-C had the same reactivity with the mutated polypeptide as with the wild-type molecule, but reactivity with two other anti-C examples was reduced by 50 percent. CONCLUSIONS: The nature of polymorphic residue 226 (proline when E is expressed, alanine when e is expressed) has a marked effect on the epitopes recognized by the three C MoAbs studied. The presence of Cys16 in Ce polypeptides influences the presentation of the C epitope recognized by two of the three MoAbs. These experiments provide the first direct demonstration that C and E/e antigens can be expressed on the same polypeptide.

3300. Sobao Y. Tomiyama H. Nakamura S. Sekihara H. Tanaka K. Takiguchi M. Visual demonstration of hepatitis C virus-specific memory CD8(+) T-cell expansion in patients with acute hepatitis C. Hepatology. 33(1):287-94, 2001 Jan.

Abstract

Hepatitis C virus (HCV)-specific CD8(+) T cells in peripheral blood mononuclear cells (PBMCs) from patients infected with HCV were quantitatively analyzed by flow cytometry using an HLA-B*3501-HCV epitope tetrameric complex. In chronic hepatitis C, tetramer(+)CD8(+) T cells were detected at frequencies ranging from 0.05% to 0.12% of total CD8(+) T cells. The number of tetramer(+)CD8(+) T cells in acute phase PBMCs from patients with acute hepatitis C was about 3 to 5 times higher than in recovery phase PBMCs from the same patients and in PBMCs from patients with chronic hepatitis C. Expanding tetramer(+)CD8(+) T cells in PBMCs from patients with acute hepatitis C express a CD28(+)CD45RA(-) memory T-cell phenotype. In contrast, tetramer(+)CD8(+) T cells in PBMCs from patients with chronic hepatitis C did not predominantly express this phenotype. These tetramer(+)CD8(+) T cells did not have perforin in their cytoplasma. The present study visually showed that a high number of circulating HCV-specific CD8(+) T cells in acute phase PBMCs from patients with acute hepatitis C are mostly memory T cells.

3301. Teixeira R. Papatheodoridis GV. Burroughs AK. Management of recurrent hepatitis C after liver transplantation. [Review] [88 refs] Journal of Viral Hepatitis. 8(3):159-68, 2001 May.

Abstract

Hepatitis C virus (HCV) reinfection is almost universal in patients transplanted for HCV-related cirrhosis. The medium-term survival after orthotopic liver transplantation (OLT) is similar to other transplanted patients, but the long-term survival remains uncertain. The prevention and an effective treatment of progressive liver disease are the primary aims in HCV recurrence. Interferon and ribavirin, as monotherapy or in combination, have been tried to treat or prevent HCV recurrence. Preliminary studies suggest a better chance of initial HCV clearance and better results in preventing HCV recurrence with combination therapy. IFN or ribavirin, as monotherapy, may normalize liver enzymes, but only gives rise to a transient virological response, without histological improvement. Combination IFN and ribavirin may be able to prevent progression of HCV-related graft disease, but indications and duration of treatment need further evaluation. No clear association between type and dose of immunosuppressive and outcome of post-transplant HCV recurrence has been found. Strategies to minimize the effects of immunosuppressive drugs include dose reduction of all agents and the selective discontinuation of individual agents. Initial immunosuppression with a single drug may inhibit or delay the severe fibrosis, and further investigation with a single immunosuppressive regimen to evaluate the outcome of recurrent hepatitis C should be performed. The recent evidence that mycophenolate may have an antiviral effect needs a clinical confirmation. Retransplantation survival is better with early retransplantation, and for indications not directly related to viral recurrence. [References: 88]

3302. Tennant BC. Gerin JL. The woodchuck model of hepatitis B virus infection. [Review] [214 refs] Ilar Journal. 42(2):89-102, 2001.

Abstract

The woodchuck hepatitis virus (WHV) was the first of the mammalian and avian hepadnaviruses described after discovery of the virus of hepatitis B (HBV). Woodchucks chronically infected with WHV develop progressively severe hepatitis and hepatocellular carcinoma, which present as lesions that are remarkably similar to those associated with HBV infection in humans. The initial virological studies and studies of pathogenesis utilized woodchucks that had been trapped in the wild and had acquired WHV infection naturally. Research with wild woodchucks was complicated by lack of knowledge of their backgrounds (e.g., dietary history, exposure to parasites or environmental toxins, and source and duration of WHV infection). Breeding colonies of woodchucks have been established and maintained in laboratory animal facilities, and laboratory-reared woodchucks are superior for experimental studies of pathogenesis or hepatocarcinogenesis. It is possible to infect neonatal woodchucks born in the laboratory with standardized inocula and produce a high rate of chronic WHV carriers that are useful for controlled investigations. WHV has been shown experimentally to cause hepatocellular carcinoma, supporting conclusions based on epidemiological and molecular virological studies that HBV is an important etiological factor in human hepatocarcinogenesis. Chronic WHV carrier woodchucks have become a valuable animal model for the preclinical evaluation of antiviral therapy for HBV infection, providing useful pharmacokinetic and pharmacodynamic results in a relevant animal disease model. It also has been shown that the pattern of toxicity and hepatic injury observed in woodchucks treated with certain fluorinated pyrimidines is remarkably similar to that observed in humans that were treated with the same drugs, suggesting the woodchuck has significant potential for the preclincial assessment of antiviral drug toxicity. [References: 214]

3303. Torre F. Giusto R. Grasso A. Brizzolara R. Campo N. Sinelli N. Balestra V. Picciotto A. Clearance kinetics of hepatitis C virus under different antiviral therapies. Journal of Medical Virology. 64(4):455-9, 2001 Aug.

Abstract

Interferon alpha (IFN) has been the standard treatment for hepatitis C virus (HCV) infection. Using the kinetic curves of viral clearance, this study compared three treatment regimes based on IFN alone or in combination with Amantadine or Ribavirin to determine the mechanisms of action and the most suitable way to use these drugs. The early clearance kinetics of HCV were studied in 22 patients with chronic hepatitis C under different antiviral treatments: IFN 3 MU daily (7 pts); IFN 3 MU daily plus Amantadine 200 mg (7 pts); and IFN 3 MU daily plus Ribavirin 1-1.2 gr (8 pts), for 6 months. HCV-RNA was assessed qualitatively and quantitatively on serial samples. The HCV-RNA decay curves suggested a different behaviour of viral clearance induced by the three treatments. While no significant differences were present in the first 6 hours, between 6 to 12 hours Ribavirin induced a rapid decline in the viral load. Amantadine seemed to accelerate it in the third phase (12 to 30 hours) and to provoke a more pronounced viral decline when compared to IFN alone (P < 0.05) or to IFN plus Ribavirin (P < 0.025) (baseline to 30 hours). Thus, while IFN remains the principal antiviral drug, Amantadine upholds the viral decline. Ribavirin, although synergistic with IFN, does not seem to improve the IFN effect during the earliest phase of treatment but probably supports the effects of IFN later on. A new dynamic approach to HCV treatment can therefore be developed. Copyright 2001 Wiley-Liss, Inc.

3304. Walsh K. Alexander GJ. Update on chronic viral hepatitis. [Review] [101 refs] Postgraduate Medical Journal. 77(910):498-505, 2001 Aug.

Abstract

Many recent and significant advances in the field of chronic viral hepatitis, including therapy, suggest that an update on chronic hepatitis is timely. Chronic hepatitis B virus infection remains a significant worldwide cause of liver cirrhosis and hepatocellular carcinoma, despite the wide availability of a long established and effective vaccine. Transmission occurs via perinatal, sexual, and parenteral routes (particularly intravenous drug abuse and although blood products still carry a risk, this is now extremely low in Western countries). Only a minority of infected adult cases develop chronic hepatitis but in children under 1 year, 90% develop chronic hepatitis. The clinical spectrum of chronic liver injury ranges from mild inflammation to end stage liver cirrhosis. Interferon alfa has been the mainstay of treatment for patients with active disease but nucleoside analogues (lamivudine and adefovir) are now available with similar efficacy. Patients with end stage liver disease and hepatocellular carcinoma can be offered transplantation but infection in the graft is commonplace. The combination of hepatitis B immunoglobulin and newer antiviral drugs reduce the incidence and severity of graft infection significantly.The hepatitis C virus epidemic of the latter half of the 20th century now affects more than 1% of populations worldwide. This RNA virus is spread parenterally and is becoming the leading indication for liver transplantation. The majority of patients develop chronic hepatitis, which may be progressive, evolving to significant liver disease (cirrhosis or hepatocellular carcinoma) in about 20% cases after decades. Treatment with the combination of interferon alfa and ribavirin is successful in up to 40% cases. Liver transplantation is a therapeutic option for some but graft infection is universal and often complicated by progressive liver fibrosis. A vaccine remains a remote prospect so that prevention is crucial.Hepatitis D virus infection occurs on a background of hepatitis B virus infection and can also cause liver damage. The response to antiviral therapy is poor.The newer "hepatitis" viruses G and TT do not cause significant liver injury. [References: 101]

3305. Wang QM. Heinz BA. Recent advances in prevention and treatment of hepatitis C virus infections. [Review] [159 refs] Progress in Drug Research. Spec No:79-110, 2001.

Abstract

Hepatitis C virus (HCV) is the leading cause of chronic hepatitis in humans. As members of the flavivirus family, HCVs are a group of small single-stranded, positive-sense RNA viruses. Upon translation of the genome, a polyprotein precursor is synthesized and further processed by both cellular and viral proteases to generate functional viral proteins. Treatment options are currently limited to the administration of alpha-interferon alone or in combination with ribavirin. Unfortunately, these approaches are characterized by relatively poor efficacy and an unfavorable side-effect profile. Therefore, intensive effort is directed at the discovery of novel molecules to treat this disease. These new approaches include the development of prophylactic and therapeutic vaccines, the identification of interferons with improved pharmacokinetic characteristics, and the discovery of novel drugs designed to inhibit the function of three major viral proteins: protease, helicase and polymerase. Finally, the HCV RNA genome itself, particularly the IRES element, is being actively exploited as an antiviral target using antisense molecules and catalytic ribozymes. This review summarizes the most recent findings in each of these areas. Although not intended to be comprehensive, it should serve as a first resource for those individuals who desire updated information in this rapidly changing field. [References: 159]

3306. Weber B. Melchior W. Gehrke R. Doerr HW. Berger A. Rabenau H. Hepatitis B virus markers in anti-HBc only positive individuals. Journal of Medical Virology. 64(3):312-9, 2001 Jul.

Abstract

Isolated reactivity to hepatitis B virus (HBV) core antigen (anti-HBc) is observed relatively frequently in immunocompromised individuals, intravenous drug abusers (IVDA), and in the presence of HCV infection. The reason for the lack of HBsAg is not clear. The aim of the present study was to investigate which factors (genetic variability of S gene, low-level HBsAg, and immune complexes may be responsible for the failure of HBsAg detection with commercial HBsAg screening assays. Dilution series of two recombinant HBsAg escape mutants and dilutions of serum samples from chronic HBV carriers with multiple insertions in the a determinant and different HBsAg subtypes were tested with a highly sensitive assay that detects wild-type HBsAg (Elecsys HBsAg, Roche Diagnostics, Penzberg, Germany) and two assays that detect HBV wild-type and escape mutants (Murex HBsAg Version 3, Murex and Enzygnost HBsAg 5.0, Dade Behring, Marburg, Germany). Elecsys HBsAg showed in comparison to Murex HBsAg Version 3 and Enzygnost HBsAg 5.0 a reduced sensitivity for escape mutant detection. On the other hand, the best performance for HBsAg subtype detection was obtained with Elecsys HBsAg. In the second part of the study, a selected panel of isolated anti-HBc reactive (n = 104) serum samples (AxSYM Core) was submitted to testing by Elecsys HBsAg, Murex HBsAg Version 3, Enzygnost HBsAg 5.0, and HBsAg detection after immune complex dissociation (ICD) and anti-HBs determination with two different assays (AxSYM Ausab and Elecsys Anti-HBs). To assess the specificity of anti-HBc test results, all the samples were tested by a second anti-HBc assay (Elecsys Anti-HBc). Quantitative HBV DNA detection was undertaken with a commercially available HBV PCR assay (Amplicor HBV Monitor). HCV infection was present in 65.4% of anti-HBc only reactive individuals. Five AxSYM Core positive samples were negative by Elecsys Anti-HBc. Overall, 15 (14.4%) AxSYM Ausab negative samples gave positive results with Elecsys Anti-HBs (median value: 21 IU/ml). No low-level HBsAg carrier was detected among the isolated anti-HBc reactive individuals with Elecsys HBsAg. There was no evidence for the presence of immune complexes. Only one sample was repeatedly reactive by the Murex HBsAg, suggesting that the a mutant form of HBsAg was responsible for the isolated anti-HBc reactivity, however neutralisation assay was not interpretable and HBV DNA PCR was negative. Fifteen (14.4%) anti-HBc only positive individuals were HBV DNA carriers with concentrations ranging from 800 to more than >4,000,000 copies of viral DNA/ml. In conclusion, the most probable explanations for isolated anti-HBc reactivity in our study group are a possible interference of HBsAg synthesis by HCV infection (65.4%) and divergence of results of anti-HBs assays (14.4%). There is no evidence for the presence of low-level HBsAg carriers and immune complexes. HBsAg mutants cannot be excluded definitively by the test strategy used in the present evaluation. Copyright 2001 Wiley-Liss, Inc.

3307. Wendland BE. Nutritional guidelines for persons infected with the hepatitis C virus: a review of the literature. [Review] [80 refs] Canadian Journal of Dietetic Practice & Research. 62(1):7-15, 2001 Spring.

Abstract

Hepatitis C virus (HCV) is one of the leading causes of chronic liver disease. It was first identified in 1989, as being distinct from hepatitis A and hepatitis B. The HCV does not attack the immune system, but rather causes an inflammatory reaction that is localized within the liver, involving the entire organ. About 80% of patients with acute hepatitis C will develop chronic HCV, of which about 20-30% will progress to cirrhosis and its consequences, over 10-20 years. After 20-40 years, a smaller proportion of patients with chronic disease will develop hepatocellular carcinoma. The course and outcome of the disease vary considerably. In some individuals, spontaneous remission occurs over a few years; in others, the disease is more severe, progressing to cirrhosis and end-stage liver disease. Despite biochemical and pathological confirmation of the diagnosis, patients are often asymptomatic for many years. Hepatic failure occurs late in the disease. Factors suggesting a poor prognosis include high serum transaminase levels, active cirrhosis on liver biopsy, and an increased viral load (HCV RNA), as well as associated medical conditions such as alcoholic liver disease, hepatitis B viral (HBV) infection, or human immunodeficiency virus (HIV). Nutrition has been recognized as a prognostic indicator in patients with chronic liver failure. However, standardized approaches for the diagnosis and classification of malnutrition in this population have not been consistently applied before implementing nutrition intervention. Common criteria for the assessment of malnutrition, weight and body mass index (BMI) for example, do not give accurate data in patients with chronic liver disease, complicated by ascites and edema. In addition, the chronic inflammatory reaction of liver failure progresses slowly, so that subtle nutritional deficits are not obvious at early stages of the disease. A review of the literature has been undertaken to identify current nutritional guidelines for patients with hepatitis C as well as chronic hepatitis. [References: 80]

3308. Willers E. Webber L. Delport R. Kruger M. Hepatitis B--a major threat to childhood survivors of leukaemia/lymphoma. Journal of Tropical Pediatrics. 47(4):220-5, 2001 Aug.

Abstract

This prospective descriptive study was undertaken to determine: the proportion of paediatric oncology patients with prior exposure to hepatitis B at cancer diagnosis; the risk and risk factors for acquisition of hepatitis B infection during chemotherapy; and the development of a prevention policy. Sixty African children were included in this study. At the time of cancer diagnosis, 67.7 per cent had not been exposed to hepatitis B, and none had active infection. After follow-up (median of 20 months; range 4-81 months) 23.3 per cent had active hepatitis B infection, which was subclinical in the majority of cases. The diagnosis of leukaemia/lymphoma posed a major risk factor for the acquisition of active hepatitis B infection (chi-square 7.0; p-value = 0.008), probably due to intensive chemotherapy regimens and severity of immunosuppression. No association with gender, age, place of origin, or number of blood transfusions was found. Patients with leukaemia/lymphoma were at an increased risk for horizontal transmission of hepatitis B. A policy of active surveillance for infective carriers of hepatitis B infection and passive immunization of seronegative immunosuppressed patients must be implemented to limit the endemic infection in paediatric oncology units.

Apr 02

4052. Agarwal M K, Bhatt V B, Agrawal A S : Hepatitis E. Gujarat med J 2000, 57(1), 21-3. (016248) Aug 16, 2023 No abstract.

4053. Anand P, Thakur S K, Jaiprakash M, Sharma U K, Rajvanshi A, Gill H S, Narula A S: Hepatitis C in chronic renal failure and renal transplant recipents. Indain J Gastroenterl 1999, 18(1 Suppl), S35. (016255) Aug 16, 2023

The occurrence of hepatitis C virus (HCV) infection amongst chronic renal failure (CRF) patients and renal transplant recipients was investigated over aperiod of 4 years. A total of 252 patients were studied comprising 77 chronic hemodialysis (CHD) patients, 35 CRF patients not on dialysis and 140 renal transplant recipients. Patients were screened before and after a mean 10 session of hemodialysis and their baseline and post dialysis values of liver enzymes were determined. 12(15.58%) of the 77 patients on CHD were HCV antibody positive. Similarly, among renal transplant recipients (12/140) (8.5%) were positive for HCV infection. The relative risk for hepatitis C was about 8 times greater for those with CRF compared with the normal control which makes CRF an important risk factor. This risk further increases two-fold in those on CHD. The risk for HCV infection among immunocompromised renal transplant recipients is similar to that of CRF patients in general.

4054. Arora N K, Mathur P, Arora N, Panda S K: Hepatitis C virus (HCV) infection in children in North India. Indian J Gastroenterol 1999,18(1 Suppl), S35. (016260) Aug 16, 2023

Determine the prevaience of anti- HCV antibodies in children with and without liver disease attending a tertiary care hospital in North India. Enzyme immunoassay (EIA) developed in house for detection of antibody against the prevailing HCV genotype in India was used. Specific reactivity of the test was compared with commercial 2^nd and 3^rd generation EIAs and RT-nested PCR. Prevalence of anti-HCV antibodies in children with and without liver disease. The significance of anti-HCV antibody positivity and risk factors of HCV transmission in paediatric population need further work.

4055. Arrankalle V A, Deshmukh T M, Chobe L P, Chadha M S, Walambe A M: Hepatitis G virus infection in India: prevalence and phylogenetic analysis based on 5’ non-coading region. Indian J Gastroenterol 2001,20(1), 13-17. (016259) Aug 16, 2023

Determines the prevalence of hepatitis G virus (HGV) infection in western India and carries out phylogenic analysis of HGV isolates. HGV RNA positivity rates among paid plasma donors from commercial plasmapheresis unit (7/43, 16.3%) and patients with hemophilia (5/44, 11.4%) were significantly higher than in voluntary blood donors (0/15; p=0.003 and 0.019, respectively). Among patients with acute non-A to E hepatitis and fulminant hepatic failure, 1 of 50 and 1of 28 were HGV RNA- positive, whereas 6 of 49 (12%) patients with chronic liver disease had circulating HGV RNA. All Indian isolates belonged to genotype 2, whereas the Kenyan isolate formed a distinct branch within genotype 1 consisting of African isolates. Results suggest existence of parenteral transmission of HGV in the Indian population. HGV was not an important cause of acute non-A to E hepatitis of hepatitis or fulminant hepatic failure among the patients investigated. Genotype 2 seems to be the most prevalent genotype in western India.

4056. Bapat S, Joshi D, Naik SS, Bavdekar A, Bhave S, Pandit A. Hepatitis B immunization in adolescent girls. Indian Pediatr 2001 Oct;38(10):1160-2 No abstract.

4057. Bouchard MJ, Wang LH, Schneider RJ. Calcium signaling by HBx protein in hepatitis B virus DNA replication. Science 2001 Dec 14;294(5550):2376-8

Hepatitis B virus (HBV) infects more than 300 million people and is a leading cause of liver cancer and disease. The HBV HBx protein is essential for infection; HBx activation of Src is important for HBV DNA replication. In our study, HBx activated cytosolic calcium-dependent proline-rich tyrosine kinase-2 (Pyk2), a Src kinase activator. HBx activation of HBV DNA replication was blocked by inhibiting Pyk2 or calcium signaling mediated by mitochondrial calcium channels, which suggests that HBx targets mitochondrial calcium regulation. Reagents that increased cytosolic calcium substituted for HBx protein in HBV DNA replication. Thus, alteration of cytosolic calcium was a fundamental requirement for HBV replication and was mediated by HBx protein.

4058. Bruno R, Sacchi P, Malfitano A, Filice G. YMDD-mutant HBV strain as a cause of liver failure in an HIV-infected patient. Gastroenterology 2001 Oct;121(4):1027-8 No abstract.

4059. Butz K, Denk C, Fitscher B, Crnkovic-Mertens I, Ullmann A, Schroder CH, Hoppe Seyler F. Peptide aptamers targeting the hepatitis B virus core protein: a new class of molecules with antiviral activity. Oncogene 2001 Oct 4;20(45):6579-86

A substantial proportion of the worldwide liver cancer incidence is associated with chronic hepatitis B virus (HBV) infection. The therapeutic management of HBV infections is still problematic and novel antiviral strategies are urgently required. Using the peptide aptamer screening system, we aimed to isolate new molecules, which can block viral replication by interfering with capsid formation. Eight peptide aptamers were isolated from a randomized expression library, which specifically bound to the HBV core protein under intracellular conditions. One of them, named C1-1, efficiently inhibited viral capsid

formation and, consequently, HBV replication and virion production. Hence, C1-1 is a novel model compound for inhibiting HBV replication by blocking capsid formation and provides a new basis for the development of therapeutic molecules with specific antiviral potential against HBV infections.

4060. Carroccio A, Giannitrapani L, Soresi M, Not T, Iacono G, Di Rosa C, Panfili E, Notarbartolo A, Montalto G. Guinea pig transglutaminase immunolinked assay does not predict coeliac disease in patients with chronic liver disease. Gut 2001 Oct;49(4):506-11

BACKGROUND: It has been suggested that serological screening for coeliac disease (CD) should be performed in patients with chronic unexplained hypertransaminasaemia. AIMS: To evaluate the specificity for CD diagnosis of serum IgA antitissue transglutaminase (tTG) determination in consecutive patients with chronic hypertransaminasaemia using the most widely utilised ELISA based on tTG from guinea pig as the antigen. PATIENTS AND METHODS: We studied 98 patients with chronic hypertransaminasaemia, evaluated for the first time in a hepatology clinic. Serum anti-tTG and antiendomysial (EmA) assays were performed. Patients positive for EmA and/or anti-tTG were proposed for intestinal biopsy. Finally, all sera were reassayed for anti-tTG using an ELISA based on human recombinant tTG as the antigen. RESULTS: A total of 94/98 hypertransaminasaemic patients were positive for hepatitis virus markers, with 82/98 (83%) positive for anti-hepatitis C virus. Liver histology showed that most patients had mild or moderate chronic hepatitis while severe fibrosis or overt liver cirrhosis was found in 20/98. CD screening showed that 15/98 (16%) hypertransaminasaemic subjects had anti-tTG values in the same range as CD patients; however, IgA EmA were positive in only 2/98 (2%). Distal duodenal biopsy, performed in nine patients, showed subtotal villous atrophy in the two EmA+/anti-tTG+ patients but was normal in 7/7 EmA-/anti-tTG+ subjects. The presence of anti-tTG+ values in EmA- patients was unrelated to particular gastrointestinal symptoms, other associated diseases, severity of liver histology, or distribution of viral hepatitis markers. There was a significantly higher frequency of positive serum autoantibodies (antinuclear, antimitochondrial, antismooth muscle, and anti-liver-kidney microsomal antibodies) in anti-tTG+/EmA- patients than in the other subjects (9/13 v 10/83; p<0.003). Also, a correlation was found between serum gamma globulin and anti-tTG values (p<0.01). When sera were tested with the ELISA based on human tTG as the antigen, no false positive results were observed: only the two EmA+ patients with atrophy of the intestinal mucosa were positive for anti-tTG while all others were negative, including those false positive in the ELISA based on guinea pig tTG as the antigen. CONCLUSIONS: In patients with elevated transaminases and chronic liver disease there was a high frequency of false positive anti-tTG results using the ELISA based on tTG from guinea pig as the antigen. Indeed, the presence of anti-tTG did not correlate with the presence of EmA or CD. These false positives depend on the presence of hepatic proteins in the commercial tTG obtained from guinea pig liver and disappear when human tTG is used as the antigen in the ELISA system. We suggest that the commonly used tTG ELISA based on guinea pig antigen should not be used as a screening tool for CD in patients with chronic liver disease.

4061. Chedid A, Sung CC, Lepe MR, Ahmed SA, Iftikhar SA, Feller A, Beaman KD. Expression of a novel protein by regenerating hepatocytes and peripheral blood lymphocytes. Clin Diagn Lab Immunol 2001 Nov;8(6):1292-4

Regeneration and tolerance factor (RTF) is a protein with immunosuppressive activity and is normally present in the thymus and placenta. RTF was measured in the livers of patients with regenerating nodules due to alcoholic cirrhosis and hepatitis C. RTF was expressed in the regenerating nodules of 26 patients with alcoholic cirrhosis. All patients with chronic hepatitis C without cirrhosis failed to express RTF. Flow cytometry revealed upregulation of RTF on the lymphocytes from alcoholic cirrhosis and downregulation in hepatitis C disease.

4062. Chen GG, Lai PB, Chak EC, Xu H, Lee KM, Lau WY. Immunohistochemical analysis of pro-apoptotic Bid level in chronic hepatitis, hepatocellular carcinoma and liver metastases. Cancer Lett 2001 Oct 22;172(1):75-82

Bid, a member of the Bcl-2 family, mediates apoptosis by inducing the release of proapoptotic factors. The expression of Bid in liver diseases has not been investigated. This study evaluated Bid level in various liver diseases including hepatocellular carcinoma (HCC), liver metastases from colorectal cancer, chronic hepatitis and liver cirrhosis. The expression of Bid in tumorous tissues of HCC was lower than that in their corresponding non-tumorous tissues from the same patient. Heavy staining with Bid antibody was found in some localized tumorous liver tissues from patients with poorly differentiated tumors. In patients with chronic hepatitis and liver cirrhosis, there were gradient tumor-development centers, a gradient increase in reaction with Bid antibody from the middle of the center to its edge. The gradient tumor-development center was also found in non-tumorous tissues of HCC, suggesting that occurrence of this center in chronic hepatitis might be an early pathologic sign of HCC development. Bid was also expressed in the epithelial cells in tissues from liver metastases and their expression was often stronger than in the non-tumorous liver tissues. Heavy nuclear staining of Bid was not uncommon in these metastatic cells. The different patterns of staining between primary and secondary liver tumors may reflect a difference in tumor origin and in cell type. Nuclei of metastatic cells, though positive for Bid, still showed a considerable mitotic activity, indicating that they were in active proliferation rather than on a pathway deemed to be apoptotic. In conclusion, this study shows that the Bid level is decreased in HCC except in poorly differentiated HCC in which cells may undergo a process of apoptosis or necrosis. The existence of gradient tumor-development center in chronic hepatitis, liver cirrhosis and non-tumorous tissues from HCC may serve as a pathologic marker of a carcinogenic change of cell phenotypes.

4063. Choudhuri G, Saraswat V A, Lakhtakia S, Dadhich S K, Mehrotra P, Naik S R: Poor response to low dose interferon therapy in chronic liver disease due to hepatitis B virus infection in Indian patients. Indian J Gastroenterol 1999, 18(1 Suppl), S26. (016288) Aug 16, 2023

Assesses virological and clinical response of low dose interferon therapy in patients of established hepatitis B related chronic liver disease in north India. 19 consecutive patients of chronic active hepatitis with (all Child Pugh class A) or without cirrhosis, with elevated transminases (ALT ³ x 1.5 normal) and presence of HbeAg and /or HBV DNA in the serum were offered treatment with IFN a 2b TIW (or 3 MU when 5 MU was not tolerated ) for 24 weeks. Therapy has been completed also received lamivudine 150 mg OD for 24 weeks, one has completed treatment. 12 patients completed 24 weeks of therapy. Initial biochemical remission occurred in 9 (75%) with break-through in 3 (25%). End of treatmentvirological response was observed in 7 (58%) with absence of HBV DNAin serum by PCR; however there was biochemical relapse with increase in ALT in 2 patients within 3 months of stopping treatment. Sustained virological response occurred at 6 months or more after end of therapy in 5 (42%), 2 of whom also lost the HBsAg at 6-18 months. The eradication rate of hepatitis B with low dose IFN therapy is 42%. Probably higher doses or combination regimes with nucleoside analogues need to be tried to obtain better results.

4064. Comanor L, Anderson F, Ghany M, Perrillo R, Heathcote EJ, Sherlock C, Zitron I, Hendricks D, Gordon SC. Transcription-mediated amplification is more sensitive than conventional PCR-based assays for detecting residual serum HCV RNA at end of treatment. Am J Gastroenterol 2001 Oct;96(10):2968-72

OBJECTIVE: In patients chronically infected with hepatitis C virus (HCV) undergoing antiviral therapy, sustained virologic response is suggested by viral clearance by end of treatment (EOT). Viral clearance is defined by nondetection of serum HCV RNA, usually by qualitative PCR-based assays with limits of detection ranging from 100 to 1000 copies/ml. However, some individuals relapse after achieving apparent viral clearance by EOT. These individuals may have low levels of viremia not detected by current PCR methods. The aim of this retrospective study was to determine whether the Bayer HCV RNA Qualitative Assay, which employs Transcription Mediated Amplification (TMA) and detects 50 HCV RNA copies/ml, could detect residual serum HCV RNA in patients who achieved apparent viral clearance by EOT and subsequently relapsed. METHODS: Samples were obtained at EOT (wk 24 or 48) and follow-up (wk 24-26 posttreatment) from 97 patients treated for HCV (78 relapsing patients, 19 sustained responders). All samples in which HCV RNA was not detected by PCR were tested in a blinded manner for HCV RNA by the TMA-based assay. RESULTS: HCV RNA was detected by the TMA-based assay in 27 (34.6%) EOT and 76 (97.4%) follow-up samples from relapsing patients, but not in any of the EOT or follow-up samples from sustained responders. CONCLUSION: Residual serum HCV RNA was detected by the TMA-based assay in EOT samples from 34.6% of patients that had achieved apparent viral clearance by PCR. The detection of HCV RNA by the TMA-based assay could help redefine EOT response and assist in the antiviral management of HCV infection.

4065. Crespo J, Cayon A, Fernandez-Gil P, Hernandez-Guerra M, Mayorga M, Dominguez Diez A, Fernandez-Escalante JC, Pons-Romero F. Gene expression of tumor necrosis factor alpha and TNF-receptors, p55 and p75, in nonalcoholic steatohepatitis patients. Hepatology 2001 Dec;34(6):1158-63

The main objective of this study was to analyze the pathogenic role of the tumor necrosis factor alpha (TNF-alpha) system in the development of nonalcoholic steatohepatitis (NASH). Fifty-two obese patients were studied. We investigated: (1) the expression of mRNA of TNF-alpha and their p55 and p75-receptors by quantitative reverse-transcriptase polymerase chain reaction (RT-PCR) in hepatic and adipose tissues; and (2) the relationship between TNF-alpha, p55, and p75 and the severity of NASH. Obese patients without NASH were the control group. A remarkable increase in the expression of mRNA of TNF-alpha was found in patients with NASH in hepatic tissue (0.65 +/- 0.54) and in peripheral fat (0.43 +/- 0.45); in the control samples, the mRNA expression was 0.28 +/- 0.32, P <.007, and 0.26 +/- 0.22, P <.018, respectively. Furthermore, we found a significant increase in the mRNA levels of p55 receptor (2.42 +/- 1.81 vs. 1.56 +/- 1.17; P <.05); however, the mRNA expression of the p75 receptor was similar in both patients. Those patients with NASH with significant fibrosis presented an increase in the expression of mRNA TNF-alpha in comparison with those with a slight or nonexistent fibrosis. An overexpression of TNF-alpha mRNA is found in the liver and in the adipose tissue of NASH patients. The levels of mRNA-p55 are increased in the liver tissue of NASH patients. This overexpression is more elevated in patients with more advanced NASH. These findings suggest that the TNF-alpha system may be involved in the pathogenesis of NASH.

4066. Davis GL. Treatment of chronic hepatitis C. BMJ 2001 Nov 17;323(7322):1141-2 No abstract.

4067. De Silvestri A, Pasi A, Martinetti M, Belloni C, Tinelli C, Rondini G, Salvaneschi L, Cuccia M. Family study of non-responsiveness to hepatitis B vaccine confirms the importance of HLA class III C4A locus. Genes Immun 2001 Nov;2(7):367-72

Non-responsiveness to hepatitis B virus (HBV) vaccine in adults is strongly associated with HLA-C4AQ0,DRB1*0301,DQB1*02 haplotype. This association was also demonstrated in neonates who failed to mount a humoral response to challenge with HBV vaccine. About 4% of vaccinated newborns do not reach a protective antibody level (> or =10 mIU/ml) at seroconversion and 0.4% is a non-responder even after receiving a fourth dose of vaccine (true non-responders (TNR)); while 3.6% achieved an antibody level > or =10 mIU/ml (slow responders (SR)) only when reboostered with the fourth dose. In the present study we extend the vaccination and HLA typing to 91 family members of probands to understand better the possible parent-to-child transmission of this trait. A transmission disequilibrium test (TDT), performed in 27 families, showed that the C4AQ0 allele was almost always transmitted to probands, both TNRs and SRs. Although not statistically significant, the highest LOD score was obtained with C4A locus: 1.58. These results suggest the presence of a region regulating immune response against HBV vaccination near to or coincident with the C4A locus.

4068. Faustini A, Spadea T, Fano V, Giorgi Rossi P, Sangalli M, Franco E, Perucci CA. Factors associated with hepatitis B virus immunization coverage at the beginning of a population campaign in the Lazio region, Italy. Prev Med 2001 Nov;33(5):409-14

BACKGROUND: The hepatitis B virus (HBV) vaccination was introduced in Italy in 1991 as compulsory among newborns and among 11-year-old children. METHODS: We conducted a retrospective study to evaluate the HBV immunization coverage of the two target populations by the public health services in the Lazio region and to analyze factors associated with starting and completing HBV immunization in the initial period of the campaign. We used data registered in the public health services of 7/51 Health Districts. As a proxy indicator of services' performance we used the "expected immunization period," that is, the 6-month period in which each child should have been started on immunization, according to the calendar. RESULTS: HBV vaccine coverage rates were 63% in the younger cohort and 50% in the older one. The results of univariate and multivariate regression analysis showed that starting HBV immunization was associated with being newborn (crude OR = 3.30; 95%CI 2.17-2.44), with living in a small city (crude OR = 6.81; 95%CI 6.12-7.58), and with being assigned to the second (crude OR = 1.77; 95%CI 1.65-1.90) or to the third 6-month period of the expected immunization period (crude OR = 2.58; 95%CI 2.42-2.76). The probability of completing HBV immunization was higher among children who had had the first dose "age-appropriately" or with "acceptable delay" and among those living in small cities. It was lower among children in the second or the third 6-month period. Size of urban area of residence was associated with both outcomes: the city of Rome showed the lowest probabilities of starting and completing HBV immunization, while the small cities showed the highest ones. CONCLUSIONS: The performance of public health services was the most important determinant of recourse to public health services for vaccinations; it varied according to size of urban area; in towns organization difficulties contributed to the delay of starting vaccination, for at least a year. The expected immunization period was a good proxy indicator of services' performance. The timing of the first dose was the strongest predictor of completing vaccination also at the beginning of the campaign. Copyright 2001 American Health Foundation and Academic Press.

4069. Friebe P, Lohmann V, Krieger N, Bartenschlager R. Sequences in the 5' nontranslated region of hepatitis C virus required for RNA replication. J Virol 2001 Dec;75(24):12047-57

Sequences in the 5' and 3' termini of plus-strand RNA viruses harbor cis-acting elements important for efficient translation and replication. In case of the hepatitis C virus (HCV), a plus-strand RNA virus of the family Flaviviridae, a 341-nucleotide-long nontranslated region (NTR) is located at the 5' end of the genome. This sequence contains an internal ribosome entry site (IRES) that is located downstream of an about 40-nucleotide-long sequence of unknown function. By using our recently developed HCV replicon system, we mapped and characterized the sequences in the 5' NTR required for RNA replication. We show that deletions introduced into the 5' terminal 40 nucleotides abolished RNA replication but only moderately affected translation. By generating a series of replicons with HCV-poliovirus (PV) chimeric 5' NTRs, we could show that the first 125 nucleotides of the HCV genome are essential and sufficient for RNA replication. However, the efficiency could be tremendously increased upon the addition of the complete HCV 5' NTR. These data show that (i) sequences upstream of the HCV IRES are essential for RNA replication, (ii) the first 125 nucleotides of the HCV 5' NTR are sufficient for RNA replication, but such replicon molecules are severely impaired for multiplication, and (iii) high-level HCV replication requires sequences located within the IRES. These data provide the first identification of signals in the 5' NTR of HCV RNA essential for replication of this virus.

4070. Goddard S, Williams A, Morland C, Qin S, Gladue R, Hubscher SG, Adams DH. Differential expression of chemokines and chemokine receptors shapes the inflammatory response in rejecting human liver transplants. Transplantation 2001 Dec 27;72(12):1957-67

BACKGROUND: Graft rejection after liver transplantation is associated with a lymphocytic infiltrate, the nature of which will be determined by, among various factors, the local activity of chemokines that attract particular subsets of effector cells to the graft. METHODS: The expression of chemokines and receptors in human liver allografts was studied by immunohistochemistry of tissue and flow cytometry of blood and liver-derived lymphocytes. Receptor function was assessed with in vitro chemotaxis. RESULTS: We report increased expression of chemokine

receptors CXCR3, CXCR4, and CCR5 on circulating and graft-infiltrating

lymphocytes after liver transplantation. Liver-derived T cells responded to the ligands for these receptors in vitro, which suggests that the receptors are functionally active. The chemokine ligands for these receptors were detected in rejecting allografts. CXCR3 ligands interferon-inducible protein 10 and monokine-induced by gamma interferon were detected on sinusoidal endothelium and interferon-inducible T-cell alpha chemoattractant was detected on portal and hepatic vascular endothelium, whereas the CXCR4 ligand, stromal-derived factor (SDF), was restricted to biliary epithelium. CCR5 ligands have previously been shown on portal endothelium. An in vitro model of T-cell alloactivation demonstrated a similar pattern of expression of functional CXCR3, CXCR4, and CCR5 on T cells. Increased expression of chemokine receptors, especially CCR3 and CCR5, was associated with redistribution of activated Kupffer cells in rejecting grafts. CONCLUSIONS: The patterns of chemokine expression in liver allografts during rejection suggest that the recruitment and positioning of lymphocytes is mediated by specific chemokines. Although ligands for the receptors CXCR3 and CCR5 are important for recruitment, the restriction of SDF to bile ducts suggests that CXCR4 may be involved in the retention of alloactivated lymphocytes at sites of graft damage.

4071. Govindarajan R, Naik S: Modulation of tumor necrosis factor-( production by hepatitis B virus in human monocytic cell line, THP-1. Indian J Gastroenterol 1999, 18(1 Suppl), S22. (016330) Aug 16, 2023

Viruses can modulate the immune response by coding for cytokines, chemokines (virokines), cytokine receptors (viraceptors), MHC class I homologues and many other molecules of immunological significance. Viruses can alter the state of activation/death of cells. Certain viruses can directly (LTRs of retro viruses) or indirectly (transactivating proteins of HBV, HIV) regulate the gene expression in the host cells. Extra-hepatic infection by hepatitis B virus which belongs to the hepadna viridae family, is well documented. Since HBx protein can transactivate viral and host cellular genes and the recent observation that PMBCs can be infected by HBV, investigated the possibility that HBV genes may transactivate expression of TNF-a in infected cells. As a model, human monocytic cell line THP-1 was transfected with plasmids expressing X and SIS2S genes of HBV. Spontaneous and LPS-induced TNF-% production by these cells was quantified by ELISA. HBx transfected THP-1 cells produced 25 to 95% more TNF than the HBSIS2S transfected cells and controls. The results indicate that X gene of HBV upregulates TNF-a production by THP-1. This may be relevant to the pathogenesis of HBV- induced chronic liver disease.

4072. Greenberg DP. Considerations for hepatitis B as part of a combination vaccine. Pediatr Infect Dis J 2001 Nov;20(11 Suppl):S34-9

BACKGROUND: In 1991 the Advisory Committee on Immunization Practices (ACIP) developed a comprehensive strategy to eliminate the transmission of hepatitis B virus in the United States, which includes immunization of all infants. Today, as the number of recommended childhood vaccinations increases, combination vaccines are needed to simplify the immunization schedule and improve coverage levels. METHODS: A review of the literature was performed to determine the considerations that should be taken when hepatitis B virus vaccine (HepB) is included as part of a combination vaccine. RESULTS: A combination vaccine that incorporates HepB and other routine infant vaccine antigens has been developed for administration at 2, 4 and 6 months of age. Clinical studies have demonstrated that administration of HepB, either as a monovalent or combination vaccine at 2, 4 and 6 months of age, induces a seroprotective immune response similar to that achieved with monovalent HepB administered at 0, 1 and 6 months of age. In addition the combination vaccine results in similar or fewer adverse reactions compared with separate administration of its components. Infants given a dose of monovalent HepB at birth will receive a total of four doses of HepB when the combination is used. The extra dose of HepB has not led to increased adverse reactions. CONCLUSIONS: A HepB-containing combination vaccine administered at 2, 4 and 6 months of age is as safe and immunogenic as separate administration of its components and will help simplify the childhood immunization schedule.

4073. Gupta DK, Charles AR, Srinivas M, Dave S, Bal CS. Betamethasone in plus phenobarbitone prior to hepatobiliary scintigraphy increases diagnostic accuracy in infants with jaundice. Indian J Pediatr 2001 Nov;68(11):1039-41

OBJECTIVE: In the diagnostic work up of the child with neonatal obstructive cholangiopathy (NOC), hepatobiliary scintigraphy (HBS) determines the need for peroperative cholangiography (POC). Traditionally, phenobarbitone is recommended to prime the liver to HBS. This retrospective study was designed to evaluate whether addition of the betamethasone (BM) alters the diagnostic accuracy of the HBS in distinguishing neonatal hepatitis (NH) from extra hepatic biliary atresia (EHBA). METHODS: Between 1993-1999, 202 patients presented with NOC and this study was not designed as a prospective randomized clinical trial. Of these, 126 patients had received Phenobarbitone (Group I) and the remaining 76 (Group II) had received BM in addition to the PB in a dose of 5 mg/k/d and 2.2 mg/k/d respectively for 7 days prior to HBS. RESULTS: Retrospective analysis revealed that, in the Group I, 41 showed excretion and 85 did not show any excretion of the radiopharmaceutical and the latter underwent POC which revealed that 31 patients (36%) of them showed patent biliary tract. In group II, 32 patients revealed excretion and 44 did not show any excretion of the radiopharmaceutical and the latter had undergone POC, which revealed that only 8 patients (18%) showed patent biliary tract. The percentages of false positives (36% vs 18%) was statistically significant (p < 0.03). CONCLUSION: Addition of BM increases the diagnostic accuracy of the HBS and this would lead to decreased need for POC to distinguish NH from EHBA.

4074. Harjeet Singh, Pradhan M, Naik S: Antibody response to hepatitis B vaccine in thalassemic children. Indian J Gastroenterol 1999, 18(1 Suppl), S22. (016341) Aug 16, 2023

Multiple transfused thalassemic children have high risk of acquiring blood born infections such as hepatitis B Virus (HBV), HIV. These children are vaccinated to check against HBV infection. The study was undertaken to assess the prevalence of markers of hepatitis B Virus immunity and infection in thalassemic children. Sixty-one thalassemic children (median age 5.8 yr.) studied were given prophylactic HBV vacccination (Engerix-B) at 0,1 and 6 months interval. Of the 61, 55 (90.16%) showed response to the vaccine and their median anti-HBs levels below the prospective level, 10 IU/L. Also,3 of non-responders were HBsAg positive. Therefore the findings suggest exposure to HBV infection in 4 children despite vaccination. Of these 3 were in the vaccine responder group, suggesting the presence of mutant viruses in these cases. These observations have implications for developing vaccination strategies against HBV infection.

4075. Jacobs RJ, Meyerhoff AS. Comparative cost effectiveness of varicella, hepatitis A, and pneumococcal conjugate vaccines. Prev Med 2001 Dec;33(6):639-45

BACKGROUND: Several state and local U.S. governments are considering making varicella, hepatitis A, and/or pneumococcal conjugate vaccination conditions of day care or school entry. These requirements will likely be issued sequentially, because simultaneous mandates exacerbate budget constraints and complicate communication with parents and providers. Cost-effectiveness assessments should aid the establishment of vaccination priorities, but comparing results of published studies is confounded by their dissimilar methods. METHODS: We reviewed U.S. cost-effectiveness studies of childhood varicella, hepatitis A, and pneumococcal conjugate vaccines and identified four providing data required to standardize methods. Vaccination, disease treatment, and work-loss costs were estimated from original study results and current prices. Estimated life-years saved were derived from original study results, epidemiological evidence, and alternative procedures for discounting to present values. RESULTS: Hepatitis A vaccine would have the lowest health system costs per life-year saved. Varicella vaccine would provide the greatest reduction in societal costs, mainly through reduced parent work loss. Pneumococcal conjugate vaccine would cost twice the amount of varicella and hepatitis A vaccines combined and be less cost effective than the other vaccines. CONCLUSIONS: Hepatitis A and varicella vaccines, but not pneumococcal conjugate vaccine, meet or exceed conventional standards of cost effectiveness. Copyright 2001 American Health Foundation and Elsevier Science.

4076. Jaiswal S P, Chitnis D S, Naik G, Jain A, Salgia P, Sepaha A: Hepatitis B and Cvirus scenario in central India. Indian J Gastroenterol 1999, 18(1 Suppl), S38-40. (016350) Aug 16, 2023

Describes the prevalence of HBV and anti-HCV antibodies in different populations in central India. Sera samples from healthy subjects, persons with liver diseases and persons receiving multiple blood transfusions were screened for HbsAg and anti-HCV antibodies by the latest generation ELISA kits. The HBsAg carrier rate among general population has been observed to be constant (around 3%), over the period of 10 years; HCV carrier rate was seen to be 1 %. Among normal pregnant females 12/911 (1.31%) were HBsAg reactive and 1/460 (0.21%) were anti-HCV antibodies reactive. In patients with liver diseases, HBV infection was detected in 39.4% of AVH cases, 40.19% CLDs cases and 8.19% among hepatic failure cases in the same group of patients. Among multitransfused CRF subjects, HBV and HCV prevalence was detected in 10% (60/600) and 27.5% (64/232) of the cases. In thalassaemia subjects, HBV and HCV prevalence was found to be 3.84% and 21.5%, respectively. The findings suggest that HBV still remains major aetiological agent among sporadic case of hepatitis while HCV has overtaken HBV in multitransfused subjects.

4077. Jhamb U, Malhotra V, Mittal S K: Hepatitis B and C in childhood chronic liver disease. Indian J Gastroenterol 1999, 18(1 Suppl), S40. (016355) Aug 16, 2023

Eighty four cases of chronic liver disease in children have been studied for evidence of hepatitis B or C infection. Out of these 14 (16.6%) were found to be HBsAg positive with 11 (78.6%) males and 3(21.4%) females. Anti HCV antibody test was available in 45 cases and out of these 4 were positive. All 4 of these were males. On child had both hepatitis B and C infection. Detailed analysis of HBsAg positive cases revealed history of jaundice in 8 (57.1%), ascites in 2 (14.3%), encephalopathy in 2(14.3% and evidence of portal hypertension in 5 (35.7%) cases. Four patients were asymptomatic clinically and the disease was diagnosed on biopsy which was done because of persistent antigenemia. Liver was firm and enlarged in 9 cases and both liver and spleen were normal in 4 (28.3%) cases. History of blood transfusion was positive in 4 (28.3) cases. Multiple family members were involved in 4 cases. Serum transaminases were increased in 5 (35.7%) patients and normal in the rest. There was poor correlation between transaminase level and severity of histological picture. Liver biopsy was done in 8 cases, out of which 6 showed a picture of chronic hepatitis and 2 had cirrhosis. In chronic liver disease due to hepatitis B, serum enzymes correlate poorly with the histology and up to 1/3^rd may have normal liver and spleen on examination.

4078. Jolivet-Reynaud C, Lesenechal M, O'Donnell B, Becquart L, Foussadier A, Forge F, Battail-Poirot N, Lacoux X, Carman W, Jolivet M. Localization of hepatitis B surface antigen epitopes present on variants and specifically recognised by anti-hepatitis B surface antigen monoclonal antibodies. J Med Virol 2001 Oct;65(2):241-9

Small hepatitis B surface antigen (HBsAg) is considered to be the best marker for the diagnosis of Hepatitis B virus infection. However, HBsAg variants with mutations within the "a" determinant may be poorly or not detected by diagnostic assays. Three anti-HBsAg monoclonal antibodies (6H6B6, 27E7F10, and 2G2G10), directed against conformational epitopes, were tested for their ability to detect the wild-type HBsAg as well as variant forms and their respective epitopes were localised on the HBsAg sequence by using the phage-displayed peptide library technology. Whereas 6H6B6 did not detect mutations T123N, S143L, D144A and G145R, 27E7F10 binding was affected by mutations P120T and G145R. In contrast, 2G2G10 reacted strongly with all tested variants including variant with the G145R mutation. Part of the 6H6B6 epitope was located in the major hydrophilic region (MHR) at residues 101-105, the 27E7F10 epitope (residues 214-219) was located near the C-terminal end of the antigen and the 2G2G10 epitope at residues 199-208, within the theoretical fourth transmembrane helix. The 2G2G10 epitope localisation brings information about the HBsAg structure and the validity of established topological models. Finally, 2G2G10 is a valuable tool for HBsAg variant detection that is used as capture phase in a new bioMerieux diagnostic assay, which is currently in development. Copyright 2001 Wiley-Liss, Inc.

4079. Joshi N, Ajit Kumar, Rao N, Girish Narayan M, Nagarjun Kumar Y R, Babu S: Efficacy of the 1st indigenously developed recombinant vaccine against hepatitis B virus in Indian subjects. Indian J Gastroenterol 1999, 18(1 Suppl), S24-5.(016356) Aug 16, 2023

Joshi N, Ajit Kumar, Rao N, Girish Narayan M, Nagarjun Kumar Y R, Babu S: Efficacy of the 1^st indigenously developed recombinant vaccine against hepatitis B virus in Indian subjects. Indian J Gastroenterol 1999, 18(1 Suppl), S24-5.(016356) Aug 16, 2023

First genetically engineered hepatitis B vaccine produced in India (Shan vac-B) has been clinically evaluated in different age groups and with different schedules. The anti HBs titers were determined using Abbott kits. The clinical trials showed 100% serocon version in version in neonates and children with geometric mean titers (GMT) of 1741.63 and 17611.35 mIU/ml after the 3^rd dose, following 0,1,2 and 0,1,6 months schedule respectively. Comparison of the indigenous vaccine with the commercially available vaccine has shown comparable seroconversion with high GMT. Comparison of 0,1,2 and 0,1,6 months schedules in adults showed 100% serocon version with antibody titers of 749.12 and 6375 mIU/ml respectively. Low dose vaccine with 10 mg in young volunteers has also shown 100% seroconversion and GMT of 1674.28 mIU/ml after 3^rd dose. Followup results in healthy adults at the end of 1 year before booster has revealed a GMT of 421.9mIU/ml after 3^rd dose. In renal failure patients vaccine combined with different doses of leucomax (colony growth stimulating factor) has shown 100% seroconversion compared to 50% observed in control group without leucomax. The safety of vaccine was established in all the studies. Thus the 1^st genetically engineered hepatitis B vaccine is clinically safe and highly immunogenic. It has been proven as the suitable vaccine for India.

4080. Kato H, Orito E, Sugauchi F, Ueda R, Gish RG, Usuda S, Miyakawa Y, Mizokami M. Determination of hepatitis B virus genotype G by polymerase chain reaction with hemi-nested primers. J Virol Methods 2001 Nov;98(2):153-9

Hepatitis B virus (HBV) has been classified into six genotypes designated A-F by sequence divergence in the entire genome exceeding 8%. Very recently, the seventh genotype was reported and named genotype G. HBV genotype G is distinct from genomes of the other six genotypes in that it possesses an insertion of 36 nucleotides in the core gene, and has been found so far in France and the United States. A method for determining HBV genotype G was developed by polymerase chain reaction (PCR) with primers deduced from the 36-nucleotide (nt) insertion in five isolates of HBV genotype G the sequences of which have been deposited in DNA databases. The validity of this method, for specifically detecting HBV genotype G, was verified on a panel consisting of 142 HBV isolates of six major genotypes and four of genotype G. A total of 540 sera containing HBV in Japan covering symptom free carriers and patients with a spectrum of chronic liver disease were tested by this method, but not a single HBV genotype G sample was found. A possible method for serological determination of hepatitis B surface antigen of genotype G is suggested, without amplification or sequencing nucleotides, which would expand epidemiological and clinical researches on HBV genotype G.

4081. Kuffner EK, Dart RC, Bogdan GM, Hill RE, Casper E, Darton L. Effect of maximal daily doses of acetaminophen on the liver of alcoholic patients: a randomized, double-blind, placebo-controlled trial. Arch Intern Med 2001 Oct 8;161(18):2247-52

BACKGROUND: Retrospective reports suggest that therapeutic doses of acetaminophen may be associated with fulminant hepatic failure and death in alcoholic patients. Millions of patients use acetaminophen; the prevalence of alcoholism in the United States is 5% to 10%. OBJECTIVE: To determine if hepatic injury was associated with maximal therapeutic dosing of acetaminophen to chronic alcohol abuse patients immediately following cessation of alcohol intake (the presumed time of maximal vulnerability). METHODS: Patients entering an alcohol detoxification center were enrolled in a randomized, double-blind,

placebo-controlled trial. Exclusion criteria were baseline values of aspartate or alanine aminotransferase greater than 120 U/L, international normalized ratio greater than 1.5, serum acetaminophen level greater than 20 mg/L, or a history of ingesting more than 4 g/d of acetaminophen. Acetaminophen, 1000 mg, or placebo was administered orally 4 times daily for 2 consecutive days and liver test results were monitored for 2 more days. Acetaminophen was not administered until the alcohol had been eliminated. RESULTS: There were 102 patients in the acetaminophen-treated group and 99 patients in the placebo-treated (control) group. Demographic data, alcohol history, and baseline blood test results were similar in both groups. The mean (SD) aspartate aminotransferase level on day 4 was 38.0 +/- 26.7 U/L in the acetaminophen-treated group and 37.5 +/- 27.6 U/L in the placebo-treated group. There were 4 patients in the acetaminophen-treated group and 5 in the placebo-treated group who developed an increase in their serum aspartate aminotransferase level to greater than 120 U/L; it did not exceed 200 U/L in any patient. The mean (SD) international normalized ratio on day 4 was 0.96 +/- 0.09 in the acetaminophen-treated group and 0.98 +/- 0.11 in the placebo-treated group. CONCLUSION: Repeated administration of the maximum recommended daily doses of acetaminophen to long-term alcoholic patients was not associated with evidence of liver injury.

4082. Li C, Candotti D, Allain JP. Production and characterization of monoclonal antibodies specific for a conserved epitope within hepatitis C virus hypervariable region 1. J Virol 2001 Dec;75(24):12412-20

Frequent mutations in hypervariable region 1 (HVR1) of the main envelope protein of hepatitis C virus (HCV) is a major mechanism of persistence by escaping the host immune recognition. HVR1 contains an epitope eliciting neutralizing antibodies. This study was aimed to prepare broadly cross-reacting, high-affinity, monoclonal antibodies (MAb) to the HVR1 C terminus of HCV with potential therapeutic neutralizing capacity. A conserved amino residue group of glycine (G) at position 23 and glutamic acid (Q) at position 26 in HVR1 was confirmed as a key epitope against which two MAbs were selected and characterized. MAbs 2P24 and 15H4 were immunoglobulin G1 kappa chain [IgG1(kappa)], cross-reacted with 32 and 30 of 39 random C-terminal HVR1 peptides, respectively, and did not react with other HCV peptides. The V(H) of 2P24 and 15H4 heavy chains originated from Igh germ line v gene family 1 and 8, respectively. In contrast, the V(L) kappa sequences were highly homologous. The affinity (K(d)) of 2P24 and 15H4 (10(-9) or 10(-8) M with two immunizing peptides and 10(-8) M with two nonimmunizing HVR1 peptides) paralleled the reactivity obtained with peptide enzyme immunoassay. MAbs 2P24 and 15H4 captured 25 of 31 (81%) HCV in unselected patients' plasmas. These antibodies also blocked HCV binding to Molt-4 cells in a dose-dependent fashion. The data presented suggest that broadly cross-reactive MAbs to a conserved epitope within HCV HVR1 can be produced. Clinical application for passive immunization in HCV-related chronic liver disease and after liver transplantation is considered.

4083. Li D, Mallory T, Satomura S. AFP-L3: a new generation of tumor marker for hepatocellular carcinoma. Clin Chim Acta 2001 Nov;313(1-2):15-9

BACKGROUND: Alpha-fetoprotein (AFP) from hepatocellular carcinoma (HCC) displays differential affinity to lectin Lens culinaris agglutinin (LCA) compared to that from chronic hepatitis/liver cirrhosis. According to their binding capability to LCA, total AFP can be separated into three different glycoforms, AFP-L1, AFP-L2, and AFP-L3. AFP-L1 is the non-LCA-bound fraction, which constitutes the major glycoform of AFP in serum of chronic hepatitis and liver cirrhosis. AFP-L3 is the LCA-bound fraction of AFP. It has been reported that malignant liver cells produce AFP-L3, even when HCC is at its early stages, and especially when the tumor mass is supplied by the hepatic artery. Clinical research has determined that AFP-L3 is a highly specific marker for HCC. The AFP-L3 can be detected in the serum of approximately 35% of the patients with small HCC (<2 cm). The AFP-L3-positive HCC has potential for rapid growth and early metastasis. Compared to imaging techniques, it has been shown to have 9-12 months of lead-time in early HCC recognition. Combined sensitivity of AFP-L3 for HCC is 56%, with a specificity of >95%. METHODS: Automated assay for measuring AFP-L3 has been developed and introduced in clinical use. The new automated method for measurement of ALP-L3 is based on liquid phase binding of the AFP-L3 glycoform with LCA and two specific monoclonal antibodies labeled with peroxidase and polysulfated tyrosine peptide, respectively. CONCLUSION: AFP-L3 is a new generation of tumor marker for HCC and yields useful information on HCC for clinical decision making.

4084. Lieber CS. Alcoholic liver injury: pathogenesis and therapy in 2001. Pathol Biol (Paris) 2001 Nov;49(9):738-52

Much progress has been made in the understanding of the pathogenesis of alcoholic liver disease, resulting in improvement of prevention and promising prospects for even more effective treatments. It continues to be important to replenish nutritional deficiencies when present but it is crucial to recognize that, because of the alcohol-induced disease process, some of the nutritional requirements change. For instance, methionine, one of the essential amino acids for humans, must be activated to SAMe but, in severe liver disease, the activity of the corresponding enzyme is depressed. Therefore, the resulting deficiencies and associated pathology can be attenuated by the administration of SAMe, but not by methionine. Similarly, phosphatidylethanolamine methyltransferase (PEMT) activity, which is important for hepatic phosphatidylcholine (PC) synthesis, is also depressed in alcoholic liver disease, therefore calling for administration of the products of the reaction. It might also be beneficial to add other compounds to such therapeutic regiment. Since free radical generation by the ethanol-induced CYP2E1 plays a key role in the oxidative stress, inhibitors of this enzyme have great promise. Several have been investigated experimentally and PPC is particularly interesting because of its innocuity. In view of the striking negative interaction between alcoholic liver injury and hepatitis C, an antiviral agent is eagerly awaited that, unlike Interferon, is not contraindicated in the alcoholic. Anti-inflammatory agents are also equired. In addition to down-regulators of cytokines and end toxic are being considered. Finally, since excess drinking is the crux of the issue, anticraving agents should be incorporated in any contemplated therapeutic cocktail, in view of the recent promising results obtained with some of these agents such as naltrexone and acamprosate.

4085. Madan K, Jain A, Jandwani P, Gupta R K, Kar P, Mathur U S: Multicentric open labelled evaluation of immunogenicity (seroprotection rate) and reactogenicity of a recombinant DNA hepatitis B vaccine of Cuban origin when administered in a two dose schedule. Indian J Gastroenterol 1999, 18(1 Suppl),S24. ) (016378) Aug 16, 2023

Study was carried out with an aim to evaluate theimmunogenicity (seroprotection rate) and reactogenicity of a novel recombinant DNA hepatitis B vaccine of Cuban origin ( Enivac HB) when administered in a two dose schedule. The study was conducted at two independent centres (New Delhi and Jaipur) and 111 healthy volunteers without any symptomatic or serological evidence of HBV infection were administered the Cuban vaccine intramuscularly in a dose of 20 mg at a day 0 and day 30. Blood samples were collected for evaluation of seroprotection at day 30,60 and 90 at both the centres and, in addition, at day 120 at New Delhi. All subjects were evaluated for any adverse event for 120 hours susequent to each dose of the vaccine. The mean age of the vaccine was 23.94 years and the male: female ratio was 61:5. An overall seroprotection rate of 24.3% was obtained at day 30, 68.5% at day 60, 94.5% at day 90 and 99.1% by day 120. The vaccine was well tolerated with no serious adverse reactions. Minor side effects such as injection site tenderness, erythema and /or low grade fever were observsd in 4.5% of the subjects. The recombinant DNA hepatitis B vaccine of Cuban origin is safe well- tolerated and highly immunogenic and only two doses of this vaccine given one month apart can provide a acceptably good seroprotection rate via-avis the conventional three-dose regimen.

4086. Mathur P, Arora N K: Consideration for HAV vaccine in India. Indian J Pediat 2001, 68(1),23-30. (016392) Aug 16, 2023 No abstract.

4087. Mawhorter SD. Who should receive hepatitis A vaccine? Cleve Clin J Med 2001 Oct;68(10):825-7 No abstract.

4088. Mele A, Tancredi F, Romano L, Giuseppone A, Colucci M, Sangiuolo A, Lecce R, Adamo B, Tosti ME, Taliani G, Zanetti AR. Effectiveness of hepatitis B vaccination in babies born to hepatitis B surface antigen-positive mothers in Italy. J Infect Dis 2001 Oct 1;184(7):905-8

This study examined 522 children born to hepatitis B surface antigen (HBsAg)-positive mothers from 1985 through 1994 and evaluated the protection provided by anti-hepatitis B virus (HBV) immunization at birth. Babies were given hepatitis B immunoglobulin and hepatitis B vaccine at birth. At 5-14 years after immunization, 17 children (3.3%) were anti-HB core antigen positive, and 3 also were HBsAg positive. One carrier child had a double mutation, with substitution of proline-->serine at codons 120 (P120S) and 127 (P127S) within the a determinant of HBsAg. Of the 522 children, 400 (79.2%) of 505 still had protective anti-HBsAg titers > or =10 mIU/mL. Thus, HBV vaccination of children born to HBsAg-positive mothers is effective and confers long-term immunity. There is no evidence that the emergence of HBV escape mutants secondary to the immune pressure against wild-type HBV is of concern.

4089. Mittal S K: Desirability and fesibility of hepatitis B vaccine in EPI. Indian J Pediat 2001, 68(1), 61-5. (016400) (No abstract) Aug 16, 2023 No abstract.

4090. Nair S, Perrillo RP. Serum alanine aminotransferase flares during interferon treatment of chronic hepatitis B: is sustained clearance of HBV DNA dependent on levels of pretreatment viremia? Hepatology 2001 Nov;34(5):1021-6

During interferon treatment of chronic hepatitis B, an alanine aminotransferase (ALT) flare may herald a sustained loss of viral replication, but the relationship between virologic response, the extent of a flare, and pretreatment hepatitis B virus (HBV) DNA level has not been defined. We retrospectively examined the impact of an ALT flare on sustained virologic response in 121 interferon-treated patients and 42 untreated controls with either low-level (<100 pg/mL) or high-level (> or =100 pg/mL) viremia. The degree of ALT flare was classified as mild (increase in ALT of 86-171 IU/L above baseline), moderate (increase of 172 to 343 IU/L above baseline), and severe (increase of > or =344 IU/L above baseline). Undetectable serum HBV DNA and hepatitis B e antigen (HBeAg) loss were significantly more likely at the end of follow-up in patients having a flare (P =.0001 and.001, respectively). In the high viremia group, a proportionate increase in virologic response was observed as the degree of flare increased. By multivariate analysis, high baseline HBV DNA, high pretreatment ALT, and both moderate and severe ALT flare were independently predictive of a virologic response with severe flare being the most powerful predictor for a sustained loss of serum HBV DNA (odds ratio, 5.3; P =.004). Severe flare was predictive of a virologic response in the high but not low viremia group. We conclude that a virologic response in patients with high-level viremia is dependent on the degree of ALT flare. Induction of a robust flare may enhance virologic response when high-level viremia is detected.

4091. Rajan S, Liebman HA. Treatment of hepatitis C related thrombocytopenia with interferon alpha. Am J Hematol 2001 Nov;68(3):202-9

Thrombocytopenia is a common extrahepatic manifestation of hepatitis C (HCV) infection. Treatment with steroids may be effective, but can exacerbate the viral infection. Interferon alpha (INF) has documented efficacy in the treatment of HCV, but its use in the treatment of HCV thrombocytopenia is controversial. We treated eight patients with HCV-related thrombocytopenia, who had platelet counts of fewer than 50 x 10(9)/l (range: 16 to 46 x 10(9)/L) with INF 3 MU SQ three times a week. Planned duration of treatment was 24 weeks. Five patients had no evidence of hepatic cirrhosis, three had cirrhosis, and two had palpable splenomegaly. Only three patients tolerated the full course of treatment, and all three had improvement in their platelet counts to greater than 50 x 10(9)/l. Two other patients had improvement in platelet counts to more than 50 x 10(9)/l with shorter duration of treatment (six and 16 weeks, respectively). The mean increase in platelet count in the five responders was 44 x 10(9)/lL (range: 28 to 90 x 10(9)/l). The average peak platelet count in the responders was 81 x 10(9)/l (range: 62 to 136 x 10(9)/l). Duration of response ranged from four to 18+ months, with the shortest responses observed in the two patients treated with a shorter course of INF. Response was independent of the presence of cirrhosis. Responding patients had improvement in hepatic transaminases, reduction in cryoglobulin and anticardiolipin antibodies, and HCV plasma RNA when tested. Relapse was associated with an increase in these laboratory markers of HCV infection. We conclude that INF can be an effective treatment in patients with HCV-related thrombocytopenia. Copyright 2001 Wiley-Liss, Inc.

4092. Ray S, Broor S, Ghosh D, Vaisnav Y, Broor S L, Dar L, Seth P: TGF ( levels in HCV related chronic liver disease as studied by semiquantitative RT-PCR. Indian J Gastroenterol 1999, 18(1 Suppl), S33. (016455) Aug 16, 2023

TGFb family of cytokines are ubiquitous and multifunctional and play an important role in growth and development, inflamation and repair and hostimmunity. The mammalian TGFb isoforms (TGF b₁, b₂, b₃) are secreted as latent precursors and have multiple cell surface receptors of which at least two- b₁ and b₂ – mediate signal transduction. It has been reported that in cases of chronic liver disease TGFb levels have been found to be upregulated. An attempt has been made to show the status of TGFb in HCV related chronic liver disease. RT-PCR for TGFb in HCV related chronic liver disease. RT-PCR for TGFbmRNA was done on liver biopsies from 4 patients of chronic liver disease due to HCV. In 1 patient of fulminant hepatic failure also TGFbmRNA was detected in biopsy. The levels of TGFb have been quantitated by semi-quantitative PCR using TGFb mimic. An increase in TGFb levels in HCV infection thus may have a role in pathogenesis of HCV related cirrhosis and hepatocellular carcinoma as is evident from clinical sample data.

4093. Sewell EC, Jacobson SH, Weniger BG. "Reverse engineering" a formulary selection algorithm to determine the economic value of pentavalent and hexavalent combination vaccines. Pediatr Infect Dis J 2001 Nov;20(11 Suppl):S45-56

INTRODUCTION: Combination vaccines with overlapping, noncomplementary components are being introduced to reduce the number of separate injections required to immunize children. A vaccine selection algorithm using operations research techniques was developed as a tool for vaccine purchasers to assemble formularies of monovalent and combination vaccines that would satisfy the recommended immunization schedule. The algorithm weighs distinguishing features of economic consequence among competing vaccines to achieve the lowest overall cost to payers and/or to society for immunization. This method was adapted here to solve for the purchase price of several hypothetical future pentavalent and hexavalent combination vaccines that would permit each to "win" a place in such a lowest cost formulary. METHODS: Integer programming and an iterative bisection search method determined the maximum "inclusion price" of 4 vaccines not licensed in the United States as of September, 2001 [diphtheria-tetanus-acellular pertussis (DTPa)-Haemophilus influenzae type b (HIB)-hepatitis B (HBV), DTPa-HIB-inactivated polio vaccine (IPV), DTPa-HBV-IPV and DTPa-HIB-HBV-IPV], in competition with 15 existing formulations of licensed vaccines for these diseases at their March, 2000, federal contract discount prices. Both 5-visit and 6-visit scenarios were studied. Different preparation costs were assigned to lyophilized powder ($1.50), liquid ($0.75) and prefilled-syringe ($0.25) formulations/packaging. Injection costs were varied stepwise from $5 through $45 for each dose administered, shifting from a payer's to a societal perspective. RESULTS: Overall inclusion prices (maximum price for each candidate vaccine to be included in a lowest cost formulary) ranged from $9 to $129 per dose depending on cost assumptions and usage frequency (values would be higher if competing against private-sector vaccine prices). The range was $27 to $68 per dose for DTPa-HIB-HBV, at optimal utilization to avoid extra vaccination. Similarly, as injection costs varied from $5 to $45, DTPa-HIB-IPV ranged from $28 to $75. With the same assumptions, DTPa-HBV-IPV would earn a place in a best value formulary at prices from $35 to $76. As expected the inclusion prices for hexavalent DTPa-HIB-HBV-IPV, $40 to $123, were higher (reflecting more economic value) than for pentavalents. When the assumed injection costs rose to > or = $8, the more expensive HIB-HBV and DTPa-HIB tended to appear in lowest cost formularies, because their cost premium over separate monovalent and trivalent products was outweighed by the savings from one fewer injection. CONCLUSION: Reverse engineering the vaccine selection algorithm provides a tool to demonstrate the economic value of new combination vaccines and to make pricing decisions.

4094. Sleijffers A, Garssen J, de Gruijl FR, Boland GJ, van Hattum J, van Vloten WA, van Loveren H. Influence of ultraviolet B exposure on immune responses following hepatitis B vaccination in human volunteers. J Invest Dermatol 2001 Nov;117(5):1144-50

Exposure to ultraviolet radiation can modulate immune responses in animal and humans. Remarkably, the ultraviolet-induced immunosuppression is not restricted to the exposed skin but is also found at other body sites, i.e., systemic immunosuppression. Effects of ultraviolet radiation on infections cannot be determined by experimentation on humans, but the effects of ultraviolet on vaccination may serve as a model. Moreover, it is important in its own right to assess whether ultraviolet radiation affects vaccination responses. In this study the effect of ultraviolet B exposure on the development of immune responses after hepatitis B vaccination in human volunteers was investigated. To this end, 191 human volunteers were vaccinated against hepatitis B with the Engerix-B vaccine. Ninety-seven of them were prior to the first vaccination exposed to ultraviolet B on 5 consecutive days with one personal minimal erythema dose per day. At several time-points before and after the ultraviolet B exposure regimen and the vaccination, blood samples were taken. Parameters for specific as well as nonspecific cellular and humoral immunity were analyzed. It was demonstrated that ultraviolet B exposure prior to hepatitis B vaccination did not alter the cellular (lymphocyte stimulation test) nor the humoral (antibody titers) immune response against hepatitis B surface antigen significantly. In contrast, contact hypersensitivity to diphenylcyclopropenone was significantly suppressed after ultraviolet B exposure, as was natural killer cell activity. These latter results confirm earlier findings and demonstrate immunosuppressive effectiveness of the ultraviolet regimen. In summary, although natural killer cell activity and contact hypersensitivity responses were suppressed, the ultraviolet B radiation protocol did not alter the humoral nor the cellular immune responses against hepatitis B surface antigen after vaccination.

4095. Thakur S K, Gupta R M, Rao M K K, Dham S K: Hepatitis B carrier-a study of possible routes of acquiring the infection. Indian J Gastroenterol 1999, 18(1 Suppl), S23. (016520) Aug 16, 2023

Seventy nine family contacts, who were HbsAg negative and had persistently normal ALT and no clinical or ultrasonographic evidence of liver disease wee vaccinated against HBV without knowing prior HBV exposure status, using a recombinant vaccine. A dose of 10 (pediatric) or 20 mg (adult) was injected at deltoid at 0, and 6 months. The anti HBs (AHBs) titres were measured using ELISA at baseline, 1, 2 and 7 mo. Subjects were divided into two groups. Gp I: Exposed, Gr II : Unexposed. AHBs titres>1 was defined as seroconversion and titres> 10IU/L as seroprotection. The seroprotective anti HBs response after the first dose (mo. 1) was significantly higher in exposed contacts. Moreover anti HBs titres were significantly higher in exposed contacts mo 1,2 and 7 after every shot of vaccine irrespective of the sex. At mo 7 non responders were 1 of 25 and 3 of 54 in gp I and II, respectively (p=ns). In exposed family contact seroprotection occurred earlier and was stronger. It resembled an anamnestic reaction. Anti Hbs titres were significantly higher in exposed contact at all times. Lowered immunogenic response was observed in non exposed contacts of the age above 40 years. @ BODY TEXT=016524 THAPAR PM, MATHUR SK, SAKSENA DS, SHAH HK (Department of Gastrointestinal Surgery, Bombay Hospital and Medical Research Centre, Mumbai): Leiomyosarcoma of inferior vein cava presenting as acute Budd-Chiari syndrome. Indian J Gastroenterol 2001, 20(1), 33-5. (cr)

4096. Torre D, Tambini R, Cadario F, Barbarini G, Moroni M, Basilico C. Evolution of coinfection with human immunodeficiency virus and hepatitis C virus in patients treated with highly active antiretroviral therapy. Clin Infect Dis 2001 Nov 1;33(9):1579-85

A retrospective analysis of data from a cohort of patients coinfected with human immunodeficiency virus (HIV) and hepatitis C virus (HCV) who were treated with highly active antiretroviral therapy (HAART) at 3 infectious diseases units in northern Italy was performed. While the patients were receiving HAART, CD4(+) cell counts significantly increased and HIV RNA serum levels decreased. However, no significant overall changes in alanine aminotransferase (ALT) levels and HCV RNA serum levels were observed. Fifteen (4.6%) of 323 patients died within 3 years of follow-up; death was related to cirrhosis in 5 patients (1.6%). No significant difference was observed between cirrhosis-related mortality and mortality related to other causes. Patients with ALT levels >4 times the normal values at initiation of HAART showed a significant decrease in ALT levels, whereas patients with normal ALT levels at initiation of HAART showed a significant increase over time, suggesting that HAART may have long-term beneficial or detrimental effects, depending on patient characteristics.

4097. Webster G, Bertoletti A. Quantity and quality of virus-specific CD8 cell response: relevance to the design of a therapeutic vaccine for chronic HBV infection. Mol Immunol 2001 Dec;38(6):467-73

Chronic hepatitis B virus (HBV) infection is a major cause of morbidity and mortality worldwide, yet currently available therapies fail to provide long-term control of viral replication in most patients. Strategies to boost the weak virus-specific T-cell response typically found in patients with chronic hepatitis B have been proposed as a means of terminating persistent HBV infection. The potential problems arising from the stimulation of virus-specific immunity in a disease caused by a non-cytopathic virus, where viral control and liver injury are mediated by the immune system, are discussed. Furthermore, the concept of augmenting the HBV-specific T-cell response, which has previously been focused solely on quantitative issues, is expanded in the light of new findings of qualitative differences in the HBV-specific CD8 cell response.

4098. Zimet GD, Kee R, Winston Y, Perkins SM, Maharry K. Acceptance of hepatitis B vaccination among adult patients with sexually transmitted diseases. Sex Transm Dis 2001 Nov;28(11):678-80

BACKGROUND: Sexually transmitted disease (STD) clinic patients are at risk for hepatitis B virus infection, but have been relatively neglected in terms of hepatitis B virus (HBV) immunization. Acceptance of HBV vaccine among patients attending an STD clinic was examined. GOAL: To evaluate potential predictors of HBV vaccine acceptance. STUDY DESIGN: In this study, 99 patients attending an STD clinic completed a brief questionnaire that addressed knowledge of STD and vaccines as well as sexual behavior. After the questionnaire, each patient was offered HBV vaccine, then interviewed to assess reasons for acceptance or refusal. RESULTS: Among the patients in this study, 23% accepted the vaccine and 11% reported prior vaccination. Acceptors were younger, had less education, and used condoms less frequently than those who refused vaccination. The reasons given for acceptance or rejection typically involved health beliefs related to infection or vaccination. CONCLUSION: The findings indicate an unacceptably low rate of HBV vaccine acceptance in a group at high risk for infection. However, some of the reasons for refusal may be modifiable through brief, targeted interventions.

4099. Zmuda JF, Wagoneer B, Liotta L, Whiteley G. Recognition of multiple classes of hepatitis C antibodies increases detection sensitivity in oral fluid. Clin Diagn Lab Immunol 2001 Nov;8(6):1267-70

Paired serum-oral fluid samples from 127 hepatitis C virus (HCV)-positive and 31 HCV-negative patients were tested for the presence of anti-HCV using the Ortho HCV 3.0 ELISA. Using the immunoglobulin G (IgG)-specific detection antibody provided with the HCV 3.0 ELISA we attained 100% sensitivity and specificity with serum samples; however, sensitivity in oral fluid samples was only 81%. By modifying the HCV 3.0 ELISA to utilize a secondary antibody cocktail that recognizes not only IgG but IgA and IgM as well, we attained 100% specificity and sensitivity with oral fluid samples.

4100. Zuckerman JN, Zuckerman AJ, Symington I, Du W, Williams A, Dickson B, Young MD; UK Hepacare Study Group. Evaluation of a new hepatitis B triple-antigen vaccine in inadequate responders to current vaccines. Hepatology 2001 Oct;34(4 Pt 1):798-802

In this double-blind, randomized, controlled study, healthcare professionals with a history of inadequate response to currently available single-antigen hepatitis B vaccines confirmed by measuring hepatitis B surface antibody titer before entry to the study were revaccinated with a 20-microg dose either of a novel triple-antigen (S, pre-S1, and pre-S2) recombinant vaccine or of a present single-antigen (S only) vaccine. Hepatitis B surface antibody titers were measured 8 weeks' post revaccination. A total of 925 individuals were randomized and vaccinated, of whom 915 (98.9%) completed the study and were included in the efficacy analysis. A single dose of the new triple-antigen hepatitis B vaccine (Hepacare) produced a successful response in over three quarters of these subjects who had not mounted an adequate response to current vaccines. The antibody response was statistically significantly superior (P =.002) to that after a single dose of current vaccines. An evaluation of the overall response showed that only the triple-antigen vaccine was able to raise the average antibody response (geometric mean titer [GMT]) to over 100 IU/L. The superior effect of the new vaccine was most pronounced in subjects who were previously complete nonresponders to currently available hepatitis B vaccines. Both vaccines were well tolerated and had similar safety profiles. This study demonstrated that in healthcare workers who had responded inadequately to at least a full course of immunization (median, 5 doses), a single 20-microg dose of a new triple-antigen vaccine induced protective antibody level in more vaccinees (P =.002) and increased the average antibody titer (GMT) in those protected successfully to a greater degree (P <.001) than a further attempt with a current vaccine (Engerix-B).

July 02

4608. Aceti A, Pasquazzi C, Zechini B, De Bac C. Hepatotoxicity development during antiretroviral therapy containing protease inhibitors in patients with HIV: the role of hepatitis B and C virus infection. J Acquir Immune Defic Syndr. 2002 Jan 1;29(1):41-8. No abstract.

4609. Almroth G, Ekermo B, Mansson AS, Svensson G, Widell A. Detection and prevention of hepatitis C in dialysis patients and renal transplant recipients. A long-term follow up (1989-January 1997). J Intern Med. 2002 Feb;251(2):119-28.

BACKGROUND: Hepatitis C is frequent problem in dialysis wards. DESIGN: A long time (1989-97) follow up of hepatitis C virus (HCV) infection in a Swedish nephrology unit was performed with anti-HCV screening, confirmatory antibody tests, viral RNA detection and molecular characterization. Case histories were reviewed with focus, onset of infection, liver morbidity and mortality. RESULTS: In October 1991, 10% (19 of 184) of the patients in the unit (haemodialysis-, peritoneal dialysis and transplanted patients) were verified or suspected HCV carriers, whilst the number at the end of 1996 was 8%, (13 of 157). Most patients were infected before 1991 but only in one case from a known HCV-infected blood donor. No new HCV infections associated with haemodialysis occurred during the study period. A total of 13 of 24 viremic patients had HCV genotype 2b, a pattern suggesting nosocomial transmission. This was further supported by phylogenetic analysis of HCV viral isolates in seven. HCV viremia was also common in patients with an incomplete anti-HCV antibody pattern as 8 of the 12 indeterminant sera were HCV-RNA positive. CONCLUSIONS: Awareness, prevention, identification of infected patients and donor testing limited transmission. Indeterminant recombinant immunoblot assays (RIBA)-results should be regarded with caution as a result of the relative immunodeficiency in uremic patients. Our data indicate nosocomial transmission in several patients.

4610. Alzahrani AJ, Vallely PJ, McMahon RF. Development of a novel nested in situ PCR-ISH method for detection of hepatitis C virus RNA in liver tissue. J Virol Methods. 2002 Jan;99(1-2):53-61. No abstract.

4611. Angelico M, Di Paolo D, Trinito MO, Petrolati A, Araco A, Zazza S, Lionetti R, Casciani CU, Tisone G. Failure of a reinforced triple course of hepatitis B vaccination in patients transplanted for HBV-related cirrhosis. Hepatology. 2002 Jan;35(1):176-81.

Long-term immunoprophylaxis with anti-HBs immunoglobulins (HBIg) is used to prevent hepatitis B (HBV) reinfection after liver transplantation for HBV-related cirrhosis. This approach is highly expensive. A recent report proposed posttransplant HBV vaccination with a reinforced schedule as an alternative strategy to allow HBIg discontinuation. We investigated the efficacy of a reinforced triple course of HBV vaccination in 17 patients transplanted for HBsAg-positive cirrhosis 2 to 7 years earlier. The first cycle consisted of 3 double intramuscular doses (40 microg) of recombinant vaccine at month 0, 1, and 2, respectively. This was followed, in nonresponders, by a second cycle of 6 intradermal 10 microg doses every 15 days. All nonresponders then received a third cycle identical to the first one. Vaccination started 4.5 months after HBIg discontinuation, and lamivudine (100 mg/day) was given throughout the study. All patients were seronegative for HBsAg and HBV-DNA (by PCR) and positive for anti-HBe, and 7 were positive for anti-HDV. After the first cycle one patient (#5, 53 years old, male) developed an anti-HBs titer of 154 IU/L, another (#12) reached a titer of 20 IU/L and the remainder had titers <10 IU/L. At month 7, patient #5 reached a titer of 687 IU/L. After the second cycle only one additional patient (#9) had a slight response (an anti-HBs titer of 37 IU/L). After the third cycle patient #9 rose to an anti-HBs titer of 280 IU/L, patient #12 dropped to 10 IU/L, and no other patient responded. In conclusion, a highly reinforced HBV vaccination program is effective only in a few patients who had liver transplants for HBV-related cirrhosis.

4612. Aoki M, Saito T, Watanabe H, Matsuo T, Saito K, Togashi H, Kawata S, Ishikawa K, Aoyama M, Kamada H, Shinzawa H. Clinical significance of a highly sensitive enzyme immunoassay of hepatitis B surface antigen using a novel electron spin resonance technique. J Med Virol. 2002 Feb;66(2):166-70.

We developed a highly sensitive enzyme immunoassay (EIA), the p-AP/HHTIO method, that detects serum hepatitis B surface antigen (HBsAg) by measuring stabilized nitroxide radicals using a novel electron spin resonance technique [Matsuo et al. (1998) Free Radic Biol Med 25:929-935]. To demonstrate the clinical significance of this method and to reveal occult hepatitis B virus (HBV) infection in patients, we used the method to analyze serum samples of 30 patients with acute or fulminant hepatitis who were negative for HBsAg by standard EIA, and those of seven chronic HBV carriers who became negative for HBsAg during a follow-up period by standard EIA. We also examined serum HBV DNA by amplification of the HBV S gene, using the polymerase chain reaction (PCR) technique. The p-AP/HHTIO method showed that 9 of 20 (45%) patients with acute hepatitis and 2 of 10 (20%) with fulminant hepatitis were positive for HBsAg; PCR detected HBV DNA in these HBsAg-positive patients. Antibody against hepatitis B core antigen was detected in one patient with fulminant hepatitis. The p-AP/HHTIO method demonstrated prolonged seropositivity of HBsAg even after standard EIA showed a loss of HBsAg in all seven HBV carriers. Our p-AP/HHTIO method is useful for screening and diagnosing HBV infection in patients with liver diseases who are negative for conventional HBV-related serological markers. Copyright 2002 Wiley-Liss, Inc.

4613. Bernstein D, Kleinman L, Barker CM, Revicki DA, Green J. Relationship of health-related quality of life to treatment adherence and sustained response in chronic hepatitis C patients. Hepatology. 2002 Mar;35(3):704-8.

Interferon therapy may exacerbate health-related quality of life (HRQL) deficits associated with hepatitis C virus (HCV) early in the course of therapy. Treatment with polyethylene glycol-modified interferon (peginterferon) alfa-2a (40 kd) provides improved sustained response over interferon alfa-2a, but its effect on HRQL is unknown. The objective of this study was to (1) evaluate the effect of sustained virologic response on HRQL in patients with HCV and (2) determine whether impairment of HRQL during treatment contributes to early treatment discontinuation. Data consisted of a pooled secondary analysis of patients (n = 1,441) across 3 international, multicenter, open-label, randomized studies that compared peginterferon alfa-2a (40 kd) with interferon alfa-2a. ANCOVA was used to examine the effect of sustained virologic response on HRQL. Repeated-measures mixed-models ANCOVA was used to compare Fatigue Severity Scale (FSS) and SF-36 scores during treatment by treatment group. Logistic regression analysis was used to examine the association between changes at baseline in on-treatment HRQL and early treatment discontinuation. Sustained virologic response was associated with marked improvements from baseline to end of follow-up in all subjects, including patients with cirrhosis. During treatment, patients receiving peginterferon alfa-2a (40 kd) had statistically significantly better scores on both the SF-36 and FSS. Baseline to 24-week changes in fatigue and SF-36 mental and physical summary scores significantly predicted treatment discontinuation. In conclusion, sustained virologic response is associated with improvements in quality of life in patients with or without advanced liver disease. This parameter may be an important consideration in maximizing treatment adherence.

4614. Bluteau O, Beaudoin JC, Pasturaud P, Belghiti J, Franco D, Bioulac-Sage P, Laurent-Puig P, Zucman-Rossi J. Specific association between alcohol intake, high grade of differentiation and 4q34-q35 deletions in hepatocellular carcinomas identified by high resolution allelotyping. Oncogene. 2002 Feb 14;21(8):1225-32.

One of the most frequent deletions in hepatocellular carcinoma (HCC) is that involving the long arm of chromosome 4 (30 to 70% of the cases). These chromosomal deletions are closely related to hepatitis B virus (HBV) infection. A tumor suppressor gene (TSG) located on 4q has been proposed in liver carcinogenesis, but has not been identified as yet. Despite previous LOH studies focused on 4q in HCC, a clear minimal common region of deletion (MCRD) could not be delimited. To further investigate the role of chromosome 4q LOH in the pathogenesis of HCC, 85 microsatellite markers spanning chromosome 4q were systematically analysed in a series of 154 well-characterized primary liver tumors. In 59 tumors (38%), LOHs were observed for at least two adjacent markers. Analysis of 31 tumors demonstrating a partial or interstitial 4q deletion allowed to define three MCRDs of 15, 9 and 8 Mb at the 4q22, 4q34 and 4q35 regions, respectively. Seven putative candidate genes located in 4q22, DAPP1, BMPR1B, PKD2, HERC3, SMARCAD1, CEB1 and ENH were screened for mutations but no somatic alterations were identified. Search for relationships between the specific regions of deletion and clinical parameters showed a significant association between loss of the 4q34-35 region with alcohol intake (P=0.005) and with high grade of differentiation (P=0.02). These results are in contrast with the close association between HBV infection and the whole 4q LOH and reveal heterogeneity of 4q LOH in relation to different risk factors. In the light of these new findings, which link different 4q LOH regions to different etiologic factors, the molecular mechanisms underlying 4q deletions in HCC and the targeted gene(s) remain to be identified.

4615. Bonaccorso S, Marino V, Puzella A, Pasquini M, Biondi M, Artini M, Almerighi C, Verkerk R, Meltzer H, Maes M. Increased depressive ratings in patients with hepatitis C receiving interferon-alpha-based immunotherapy are related to interferon-alpha-induced changes in the serotonergic system. J Clin Psychopharmacol. 2002 Feb;22(1):86-90. No abstract.

4616. Bonkovsky HL. Iron as a comorbid factor in chronic viral hepatitis. Am J Gastroenterol. 2002 Jan;97(1):1-4. No abstract.

4617. Brinster C, Chen M, Boucreux D, Paranhos-Baccala G, Liljestrom P, Lemmonier F, Inchauspe G. Hepatitis C virus non-structural protein 3-specific cellular immune responses following single or combined immunization with DNA or recombinant Semliki Forest virus particles. J Gen Virol. 2002 Feb;83(Pt 2):369-81.

The capacity of recombinant Semliki Forest virus particles (rSFV) expressing the hepatitis C virus non-structural protein 3 (NS3) to induce, in comparison or in combination with an NS3-expressing plasmid, specific cellular and humoral immune responses in murine models was evaluated. In vitro studies indicated that both types of vaccine expressed the expected size protein, albeit with different efficacies. The use of mice transgenic for the human HLA-A2.1 molecule indicated that the rSFV-expressed NS3 protein induces, as shown previously for an NS3 DNA vaccine, NS3-specific cytotoxic lymphocytes (CTLs) targeted at one dominant HLA-A2 epitope described in infected patients. All DNA/rSFV vaccine combinations evaluated induced specific CTLs, which were detectable for up to 31 weeks after the first injection. Overall, less than 1 log difference was observed in terms of the vigour of the bulk CTL response induced and the CTL precursor frequency between all vaccines (ranging from 1:2.6x10(5) to 1:1x10(6)). Anti-NS3 antibodies could only be detected following a combined vaccine regimen in non-transgenic BALB/c mice. In conclusion, rSFV particles expressing NS3 are capable of inducing NS3-specific cellular immune responses targeted at a major HLA-A2 epitope. Such responses were comparable to those obtained with a DNA-based NS3 vaccine, whether in the context of single or combined regimens.

4618. Buchanan D, Khoshnood K, Stopka T, Shaw S, Santelices C, Singer M. Ethical dilemmas created by the criminalization of status behaviors: case examples from ethnographic field research with injection drug users. Health Educ Behav. 2002 Feb;29(1):30-42.

The criminalization of behaviors such as the ingestion of certain mood-altering drugs creates ethical dilemmas for researchers studying those behaviors. The Syringe Access, Use, and Discard (SAUD) project is designed to uncover microcontextual factors that influence HIV and hepatitis risk behaviors of injection drug users. The article presents seven ethical dilemmas encountered using ethnographic methods: issues involving syringe replacement at injection locales, risks of participants' arrest, potential disruptions in participants' supply routes, risks of research staff arrest, threats to the protection of confidentiality, issues surrounding informed consent in working with addicts, and the confiscation of potentially incriminating information by police. The article concludes with a discussion of the limitations of traditional ethical frameworks, such as utilitarianism, for resolving these dilemmas and recommends instead improving public health professionals' capacity for practical reasoning (phronesis) through the greater use of case studies in public health curricula.

4619. Cardin R, D'Errico A, Fiorentino M, Cecchetto A, Naccarato R, Farinati F. Hepatocyte proliferation and apoptosis in relation to oxidative damage in aalcohol-related liver disease Alcohol Alcohol. 2002 Jan-Feb;37(1):43-8.

In alcohol-related liver disease, free radicals play a part in the pathogenesis of liver damage and may influence cell turnover. The aims of this study were to correlate lipid peroxidation, antioxidant defence and iron metabolism with cell proliferation and apoptosis in alcoholic liver injury, and also in comparison with virus-related liver disease. In 45 patients [10 with chronic alcoholic liver damage (CALD), 24 with HCV-related (HCV) and 11 with HBV-related chronic hepatitis (HBV)], and 10 control subjects, we investigated serum ferritin, liver tissue iron, cysteine, reduced/oxidized glutathione, malondialdehyde, histology with hepatocyte proliferation and the apoptotic index. Ferritin, iron levels and malondialdehyde were significantly higher in HCV and CALD than in HBV, and malondialdehyde correlated with both iron and ferritin. Glutathione levels were significantly lower in CALD than in HCV, HBV and control subjects, whereas cysteine levels were significantly higher. The apoptotic index was slightly lower in CALD, with apoptosis occurring more frequently in the centrilobular area, while CALD had fewer proliferating hepatocytes, both overall and in the periportal and centrilobular areas. This study confirms that chronic alcohol intake: (1) induces more peroxidative damage, which correlates with iron loading; (2) reduces antioxidant defence, lowering reduced glutathione liver availability; (3) induces an accumulation of cysteine, a glutathione precursor/metabolite in the liver, probably due to gamma-glutamyltransferase induction; (4) correlates with a lesser extent and different distribution of hepatocyte proliferation and apoptosis than in viral liver damage. This last finding may explain the different types of liver cirrhosis deriving from alcoholic liver damage and the lower cancer risk.

4620. Carvajal GP, Garcia D, Sanchez SA, Velasco MA, Rueda D, Lucena MI. Hepatotoxicity associated with the new antidepressants. J Clin Psychiatry. 2002 Feb;63(2):135-7.

BACKGROUND: Safety profiles of classical and new antidepressants are well established. Hepatotoxicity is known to occur. Recently, several cases of severe hepatic injury associated with the new antidepressants have been reported, prompting us to quantify this risk. METHOD: To estimate the cumulatve incidence of hepatic adverse reactions associated with antidepressants, we used cases of hepatic damage collected via spontaneous reporting and included in the Spanish Pharmacovigilance System database; for exposure, we have used data from drug sales to the Spanish National Health System. RESULTS: The estimated reported incidence did not show major differences for the antidepressants studied, ranging from 1.28 cases per 100,000 patient-years for sertraline to 4.00 for clomipramine, except for nefazodone, which was the agent that had the highest incidence with 28.96 cases per 100,000 patient-years. CONCLUSION: The reported incidence of hepatic adverse reactions to nefazodone seems to be higher than that estimated so far. Given the high prevalence of depression and the widespread use of antidepressants, physicians should be alert to the possibility that these medications cause hepatitis and consider early discontinuation of an antidepressant if the condition is suspected.

4621. Chamberland ME. Emerging infectious agents: do they pose a risk to the safety of transfused blood and blood products? Clin Infect Dis. 2002 Mar 15;34(6):797-805.

BACKGROUND: Safety profiles of classical and new antidepressants are well established. Hepatotoxicity is known to occur. Recently, several cases of severe hepatic injury associated with the new antidepressants have been reported, prompting us to quantify this risk. METHOD: To estimate the cumulative incidence of hepatic adverse reactions associated with antidepressants, we used cases of hepatic damage collected via spontaneous reporting and included in the Spanish Pharmacovigilance System database; for exposure, we have used data from drug sales to the Spanish National Health System. RESULTS: The estimated reported incidence did not show major differences for the antidepressants studied, ranging from 1.28 cases per 100,000 patient-years for sertraline to 4.00 for clomipramine, except for nefazodone, which was the agent that had the highest incidence with 28.96 cases per 100,000 patient-years. CONCLUSION: The reported incidence of hepatic adverse reactions to nefazodone seems to be higher than that estimated so far. Given the high prevalence of depression and the widespread use of antidepressants, physicians should be alert to the possibility that these medications cause hepatitis and consider early discontinuation of an antidepressant if the condition is suspected.

4622. Chan HL. Changing scene in hepatitis B serology interpretation. Hosp Med. 2002 Jan;63(1):16-9. Review.

Serological tests have been used in the diagnosis of hepatitis B virus (HBV) infection since the virus was first discovered. Advances in molecular biology and improvements in the understanding of HBV virology have changed the scene of hepatitis B serology interpretation.

4623. Chitturi S, Abeygunasekera S, Farrell GC, Holmes-Walker J, Hui JM, Fung C, Karim R, Lin R, Samarasinghe D, Liddle C, Weltman M, George J. NASH and insulin resistance: Insulin hypersecretion and specific association with the insulin resistance syndrome. Hepatology. 2002 Feb;35(2):373-9.

Nonalcoholic steatohepatitis (NASH) is often linked with disorders that are clearly associated with insulin resistance (IR): obesity, type 2 diabetes mellitus, and hypertriglyceridemia. We tested the hypotheses that (1) IR is an essential requirement for the development of NASH and (2) a high association between IR and liver disease is relatively specific for NASH. We measured body mass index (BMI), waist/hip ratio, and fasting serum lipid, insulin, C-peptide, and glucose levels in 66 patients with NASH (21 with advanced fibrosis and 45 with mild fibrosis). IR was determined by the homeostasis model assessment (HOMA). We also determined the strength of the association of NASH with insulin resistance syndrome (IRS) as defined by World Health Organization criteria. To assess whether the finding of IR was relatively specific to NASH rather than simply to obesity or liver disease, we compared the results of a subset of 36 patients with less-severe NASH with 36 age- and sex-matched patients with chronic hepatitis C virus (HCV) of comparable fibrotic severity. IR was confirmed in 65 patients (98%) with NASH, and 55 (87%) fulfilled minimum criteria for IRS. IR was found in lean as well as in overweight and obese patients. The IR values and the prevalence of IRS (75% vs. 8.3%) were significantly higher in those with NASH than in comparable cases of HCV. Hyperinsulinemia was attributable to increased insulin secretion rather than decreased hepatic extraction. In conclusion, most patients with NASH have IRS, and there is a near-universal association between NASH and IR irrespective of obesity. IR is present in mild as well as advanced cases of NASH but is unusual in chronic HCV of similar fibrotic severity.

4624. Cody SH, Nainan OV, Garfein RS, Meyers H, Bell BP, Shapiro CN, Meeks EL, Pitt H, Mouzin E, Alter MJ, Margolis HS, Vugia DJ. Hepatitis C virus transmission from an anesthesiologist to a patient. Arch Intern Med. 2002 Feb 11;162(3):345-50.

BACKGROUND: An anesthesiologist was diagnosed as having acute hepatitis C 3 days after providing anesthesia during the thoracotomy of a 64-year-old man (patient A). Eight weeks later, patient A was diagnosed as having acute hepatitis C. METHODS: We performed tests for antibody to hepatitis C virus (HCV) on serum samples from the thoracotomy surgical team and from surgical patients at the 2 hospitals where the anesthesiologist worked before and after his illness. We determined the genetic relatedness of the HCV isolates by sequencing the quasispecies from hypervariable region 1. RESULTS: Of the surgical team members, only the anesthesiologist was positive for antibody to HCV. Of the 348 surgical patients treated by him and tested, 6 were positive for antibody to HCV. Of these 6 patients, isolates from 2 (patients A and B) were the same genotype (1a) as that of the anesthesiologist. The quasispecies sequences of these 3 isolates clustered with nucleotide identity of 97.8% to 100.0%. Patient B was positive for antibody to HCV before her surgery 9 weeks before the anesthesiologist's illness onset. The anesthesiologist did not perform any exposure-prone invasive procedures, and no breaks in technique or incidents were reported. He denied risk factors for HCV. CONCLUSIONS: Our investigation suggests that the anesthesiologist acquired HCV infection from patient B and transmitted HCV to patient A. No further transmission was identified. Although we did not establish how transmission occurred in this instance, the one previous report of bloodborne pathogen transmission to patients from an anesthesiologist involved reuse of needles for self-injection.

4625. Czaja AJ, Donaldson PT, Lohse AW. Antibodies to soluble liver antigen/liver pancreas and HLA risk factors for type 1 autoimmune hepatitis. Am J Gastroenterol. 2002 Feb;97(2):413-9.

OBJECTIVE: Antibodies to soluble liver antigen/liver-pancreas are highly specific markers of type 1 autoimmune hepatitis that have been associated with relapse. Our aim was to determine if these antibodies are reflective of a genetic predisposition for recrudescent disease. METHODS: One hundred forty-four white North American patients were evaluated by an enzyme immunoassay and by Western blot using recombinant soluble liver antigen/liver-pancreas; 122 were assessed for class II human leukocyte antigens (HLAs). RESULTS: Twenty-two patients (15%) had antibodies to soluble liver antigen/liver-pancreas. These patients were indistinguishable from seronegative patients by clinical, laboratory, and histological features at presentation. Patients with antibodies to soluble liver antigen/liver pancreas had HLA DR3 (79% vs 50%, p = 0.02) more commonly and HLA DR4 less often (16% vs 47%, p = 0.02) than patients with smooth muscle antibodies and/or antinuclear antibodies. Seropositivity was associated with DRB1*0301 and seronegativity was associated with DRB1*0401. Relapse after drug withdrawal occurred in all patients with antibodies to soluble liver antigen/liver-pancreas and at a higher frequency than in patients with conventional antibodies (100% vs 78%, p = 0.05). CONCLUSIONS: Antibodies to soluble liver antigen/liver pancreas are associated with HLA DR3 and the susceptibility allele, DRB1*0301. Antibodies to soluble liver antigen/liver-pancreas may be surrogate markers of a genetic propensity for recrudescent disease or the target autoantigen. They may be complementary to antinuclear antibodies and smooth muscle antibodies in diagnosis and management.

4626. Dai CY, Yu ML, Chuang WL, Hou NJ, Hou C, Chen SC, Lin ZY, Hsieh MY, Wang LY, Chang WY. The response of hepatitis C virus and TT virus to high dose and long duration interferon-alpha therapy in naive chronic hepatitis C patients. Antiviral Res. 2002 Jan;53(1):9-18. No abstract.

4627. Dandri M, Burda MR, Burkle A, Zuckerman DM, Will H, Rogler CE, Greten H, Petersen J. Increase in de novo HBV DNA integrations in response to oxidative DNA damage or inhibition of poly(ADP-ribosyl)ation. Hepatology. 2002 Jan;35(1):217-23. No abstract.

4628. Di Bisceglie AM, McHutchison J, Rice CM. New therapeutic strategies for hepatitis C. Hepatology. 2002 Jan;35(1):224-31. Review. No abstract.

4629. Edstam JS, Dulmaa N, Nymadawa P, Rinchin A, Khulan J, Kimball AM. Comparison of hepatitis B vaccine coverage and effectiveness among urban and rural Mongolian 2-year-olds. Prev Med. 2002 Feb;34(2):207-14.

BACKGROUND: The prevalence of hepatitis B (HBV) carriage in Mongolia is reported to be 14%. Universal HBV immunization of newborns has been shown to decrease carriage in Asian populations. Mongolia began universal newborn vaccination in 1991. This evaluation of vaccine coverage and effectiveness compares the success of the program between urban and nomadic rural populations. METHODS: Using random cluster sampling, 148 Mongolian 2-year-olds from seminomadic rural families were compared with 127 2-year-olds from Ulaanbaatar, the capital city. RESULTS: More than 95% of all subjects received hepatitis B vaccine although rural subjects were less likely to complete the series than were urban subjects. Adequate vaccine response differed significantly: 94.2% of urban subjects versus only 70.2% of rural subjects had protective anti-HBs levels (P < 0.001). Overall the proportion of hepatitis B infection in both samples was lower than the historical Mongolian prevalence. However, unexpectedly 40% of subjects in rural Bayanhongor Aimag (Province) were found to be HBsAg positive. CONCLUSION: The Mongolian infant vaccination program for hepatitis B is successfully reducing the rate of chronic carriage in the immunized generation. However, vaccine response among rural subjects is less than that among urban. There appears to be a pocket of high disease prevalence in Bayanhongor that requires further study. Copyright 2002 American Health Foundation and Elsevier Science (USA).

4630. Fong TL, Bunnapradist S, Jordan SC, Cho YW. Impact of hepatitis B core antibody status on outcomes of cadaveric renal transplantation: analysis of United network of organ sharing database between 1994 and 1999. Transplantation. 2002 Jan 15;73(1):85-9. No abstract.

4631. Frese M, Schwarzle V, Barth K, Krieger N, Lohmann V, Mihm S, Haller O, Bartenschlager R. Interferon-gamma inhibits replication of subgenomic and genomic hepatitis C virus RNAs. Hepatology. 2002 Mar;35(3):694-703.

Persistent infection with hepatitis C virus (HCV) is a major cause of chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma. All treatments known so far rely on the antiviral activity of interferon alfa (IFN-alpha) that is given alone or in combination with ribavirin. Unfortunately, only a fraction of the patients clear the virus during therapy and for those who do not respond there is currently no alternative treatment. Selectable subgenomic HCV RNAs (replicons) have been recently used to investigate the effect of IFN-alpha on HCV replication. However, it has not yet been analyzed whether other cytokines also play a role in the innate immune response against HCV. Here we show that IFN-gamma inhibits protein synthesis and RNA replication of subgenomic and genomic HCV replicons. We further show that the inhibitory action of IFN-gamma does not rely on the production of nitric oxide or the depletion of tryptophan. In conclusion, our results suggest that cytotoxic T cells and natural killer cells may contribute to HCV clearance not only by cell killing but also by producing IFN-gamma, thereby enhancing the intracellular inhibition of viral replication.

4632. Furusyo N, Hayashi J, Kashiwagi K, Nakashima H, Nabeshima S, Sawayama Y, Kinukawa N, Kashiwagi S. Hepatitis C virus (HCV) RNA level determined by second-generation branched-DNA probe assay as predictor of response to interferon treatment in patients with chronic HCV viremia. Dig Dis Sci. 2002 Mar;47(3):535-42.

Using first- and second-generation branched-DNA probe assays (1st- and 2nd-bDNA), we investigated the predictors of favorable clinical response to interferon (IFN) treatment in patients with chronic HCV viremia. A total of 122 patients (85 genotype lb and 37 genotype 2a) with chronic HCV viremia received 24-week IFN-alpha treatment. Patients with sustained clearance of serum HCV RNA by polymerase chain reaction at six months after IFN treatment were defined as having a sustained response (SR). HCV RNA level was determined by 1st- and 2nd-bDNA assays prior to treatment. Mean HCV RNA level by 1st-bDNA was significantly higher in genotype lb patients [5.4 x 10(6) HCV genome equivalent (Meq)/ ml] than in genotype 2a patients (0.9 Meq/ml) (P < 0.05). There was no significant difference between patients with these genotypes in the level by 2nd-bDNA (1b: 5.2 Meq/ml and 2a: 3.1 Meq/ml). SR was achieved by 43 (35.2%) of 122 patients. Mean HCV RNA levels by both the 1st- and 2nd-bDNA of SR patients (1.0 and 1.9 Meq/ml) were significantly lower than those of non-SR patients (5.3 and 6.0 Meq/ml) (both P < 0.05). The SR rate in genotype 2a patients (59.5%) was significant higher than in genotype lb patients (24.7%) (P < 0.05). Stepwise logistic regression analysis showed that HCV RNA level < or = 1.0 Meq/ml by 2nd-bDNA (odds ratio = 7.6, compared to level > 1.0 Meq/ml, P < 0.05) was a significant predictive cutoff for SR. Using 2nd-bDNA, a significantly higher rate of SR was found in genotype lb patients with level < or = 1.0 Meq/ml (57.6%) than in those with level > 1.0 Meq/ml (3.8%) (P < 0.05). The SR rate of genotype 2a patients with level >1.0 Meq/ml (68.6%) was somewhat higher than for those with level < or = 1.0 Meq/ml (52.4%). These findings suggested that, using 2nd-bDNA, a low HCV RNA level of < or = 1.0 Meq/ml was the most favorable marker of successful IFN treatment and that patients with genotype 2a, even those with level >1.0 Meq/ml, had a high rate of SR to IFN treatment.

4633. Galun E, Eren R, Safadi R, Ashour Y, Terrault N, Keeffe EB, Matot E, Mizrachi S, Terkieltaub D, Zohar M, Lubin I, Gopher J, Shouval D, Dagan S. Clinical evaluation (phase I) of a combination of two human monoclonal antibodies to HBV: safety and antiviral properties. Hepatology. 2002 Mar;35(3):673-9.

Treatment of chronic hepatitis B virus (HBV) infection with interferon alfa and lamivudine is characterized by lack of viral clearance, loss of response, or emergence of drug-resistant mutants. Thus, new and multiple drug approaches are needed. We have developed two fully human monoclonal antibodies, directed against different epitopes of hepatitis B surface antigen (HBsAg) that bind to all major HBV subtypes. A phase I clinical study was conducted to evaluate the safety, tolerability, and efficacy of a mixture of these two monoclonal antibodies, HBV-AB(XTL). A total of 27 chronic HBV patients were enrolled. In part A of the study 15 patients in 5 cohorts received a single intravenous infusion of antibodies with doses ranging from 0.26 mg (260 IU) to 40 mg (40,000 IU). All patients completed 16 weeks of follow-up. In the second part of the study (part B), 12 patients in 4 cohorts received 4 weekly infusions of 10, 20, 40, or 80 mg each of HBV-AB(XTL) and were followed for 4 additional weeks. Administration of antibodies was well tolerated. Patients administered doses at an Ab:Ag molar ratio of 1:2 to 1:20 showed a rapid and significant decrease in HBsAg to undetectable levels, with a corresponding reduction of HBV-DNA levels. In part B, HBV-AB(XTL) induced a significant reduction in both HBsAg and HBV-DNA levels repeatedly after administration. In conclusion, these data suggest that HBV-AB(XTL) binds HBV particles and reduces serum viral titers and HBsAg levels. HBV-AB(XTL) could be combined with other monotherapies that are currently used to treat HBV carriers.

4634. Garcia-Retortillo M, Forns X, Feliu A, Moitinho E, Costa J, Navasa M, Rimola A, Rodes J. Hepatitis C virus kinetics during and immediately after liver transplantation. Hepatology. 2002 Mar;35(3):680-7.

The study of hepatitis C virus (HCV) kinetics after liver transplantation (LT) might be important to design strategies to prevent HCV infection of the graft. We analyzed HCV kinetics during and immediately after LT in 20 consecutive patients undergoing LT for HCV-related cirrhosis. HCV RNA was quantified in blood samples obtained at regular intervals before, during, and after transplantation. HCV-RNA concentrations decreased in 18 of 20 patients during the anhepatic phase (mean decay slope -0.92, mean HCV elimination half-life 2.2 hours). We found a significant correlation between the HCV viral load decay and the blood loss during the anhepatic phase, indicating that the observed HCV clearance rates are maximum estimates. In fact, in 1 patient with an unusually long anhepatic phase of 20 hours and with minimum blood loss, the HCV elimination half-life was 10.3 hours. Eight to 24 hours after graft reperfusion a sharp decrease in HCV viral load occurred in 19 patients (mean decay slope -0.34, mean HCV elimination half-life 3.44 hours). HCV RNA became undetectable in only 1 patient. During the following days, HCV-RNA concentrations increased rapidly in 10 patients (mean HCV doubling time 13.8 hours), remained at similar levels in 4, and continued to decrease in 6. The only variable associated with a second-phase viral load decay was the absence of corticosteroids as part of the immunosuppressive regimen. In conclusion, a sharp decrease in HCV viral load occurs during the anhepatic phase and immediately after graft reperfusion, most likely owing to a lack of virion production and hepatic viral clearance. HCV infection of the graft, however, is an extremely dynamic process and viral replication begins a few hours after LT.

4635. Goswami BB, Kulka M, Ngo D, Istafanos P, Cebula TA. A polymerase chain reaction-based method for the detection of hepatitis A virus in produce and shellfish. J Food Prot. 2002 Feb;65(2):393-402.

Outbreaks of gastroenteritis that are suspected to be of viral origin are on the rise. Thus, there is a need for regulatory agencies entrusted with food safety to develop adequate techniques for the detection of viruses in foods. We have established a general procedure for the detection of hepatitis A virus (HAV) in shellfish that, with minor modifications, is also applicable to fresh produce such as cilantro. Total RNA was isolated from shellfish or cilantro, followed by isolation of poly(A)-containing RNA. Because HAV genomic RNA contains a poly(A) tail, the isolation of poly(A)-containing RNA also enriches HAV genomic RNA. Reverse transcription was used to convert the RNA to cDNA, and then amplification was carried out by polymerase chain reaction (PCR). Reamplification with internal primers was used to improve the quality and the quantity of amplified DNA, allowing for post-PCR analysis such as sequence identification of the viral strain. With this procedure, multiple samples could be analyzed in four working days by a single trained individual. The nominal sensitivity of detection of the procedure was 0.15 TCID50 (50% tissue culture infective dose) per 0.62 g of tissue with a test virus. The direct RNA isolation protocol avoided pitfalls associated with whole-virus purification procedures by replacing virus precipitation steps involving polyethylene glycol and Procipitate with phenol extraction. The method is straightforward and reliable. We successfully used this procedure to detect naturally occurring HAV in clams involved in a gastroenteritis outbreak, as well as in cilantro artificially contaminated with a test virus.

4636. Grant MD. Antibody convergence along a common idiotypic axis in immunodeficiency virus and hepatitis C virus infections. J Med Virol. 2002 Jan;66(1):13-21.

The anti-idiotypic antibody 1F7 selectively binds antibodies against human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) gag, pol, and env proteins. We tested anti-hepatitis C virus (HCV) antibodies to investigate selection of the 1F7 idiotype on antibodies against other chronic pathogens. Twelve of 15 HCV-seropositive individuals co-infected with HIV had detectable antibodies against recombinant HCV core, 4 against HCV NS4 protein, and 3 against HCV NS3 protein. All four HCV-seropositive, non-HIV-infected individuals had antibodies against HCV core and NS4, while 3 had antibodies against NS3. The 1F7 idiotype was frequently present on antibodies against each of the HCV antigens in the HIV co-infected and non-HIV-infected groups. Antibodies against HCV, including antibodies recognizing the putative principal neutralizing determinant of HCV E2 protein, displayed skewed kappa/lambda light chain usage consistent with clonal dominance. These observations extend the association between expression of the 1F7 idiotype and abnormal B cell clonal dominance in HIV and SIV infection to HCV infection and suggest that early establishment of an oligoclonal antibody response against HCV may freeze the B cell repertoire, impair adaptation to emergent HCV variants, and favor escape from neutralizing antibodies. We also demonstrated that expression of the 1F7 idiotype extends beyond antibodies against multiple antigens of AIDS-causing retroviruses to include antibodies against multiple antigens of an unrelated chronic hepatitis virus. Thus, distinct pathogens establishing chronic infection in the face of strong humoral immune responses select antibodies along a common idiotypic axis of the immune network. Copyright 2002 Wiley-Liss, Inc.

4637. Green ST, Kinghorn GR, Goldberg DJ, Mohsen AH. The value of genitourinary medicine clinics in the recognition and diagnosis of new cases of hepatitis C in the United Kingdom. Int J STD AIDS. 2002 Jan;13(1):60-2. No abstract.

4638. Harris HE, Ramsay ME, Andrews N, Eldridge KP. Clinical course of hepatitis C virus during the first decade of infection: cohort study. BMJ. 2002 Feb 23;324(7335):450-3.

OBJECTIVE: To determine the clinical course of hepatitis C virus in the first decade of infection in a group of patients who acquired their infections on a known date. DESIGN: Cohort study. SETTING: Clinical centres throughout the United Kingdom. PARTICIPANTS: 924 transfusion recipients infected with the hepatitis C virus (HCV) traced during the HCV lookback programme and 475 transfusion recipients who tested negative for antibodies to HCV (controls). MAIN OUTCOME MEASURES: Clinical evidence of liver disease and survival after 10 years of infection. RESULTS: All cause mortality was not significantly different between patients and controls (Cox's hazards ratio 1.41, 95% confidence interval 0.95 to 2.08). Patients were more likely to be certified with a death related to liver disease than were controls (12.84, 1.73 to 95.44), but although the risk of death directly from liver disease was higher in patients than controls this difference was not significant (5.78, 0.72 to 46.70). Forty per cent of the patients who died directly from liver disease were known to have consumed excess alcohol. Clinical follow up of 826 patients showed that liver function was abnormal in 307 (37.2%), and 115 (13.9%) reported physical signs or symptoms of liver disease. Factors associated with developing liver disease were testing positive for HCV ribonucleic acid (odds ratio 6.44, 2.67 to 15.48), having acquired infection when older (at age > or = 40 years; 1.80, 1.14 to 2.85), and years since transfusion (odds ratio 1.096 per year, 1.00 to 1.20). For patients with severe disease, sex was also significant (odds ratio for women 0.38, 0.17 to 0.88). Of the 362 patients who had undergone liver biopsy, 328 (91%) had abnormal histological results and 35 (10%) of these were cirrhotic. CONCLUSIONS: Hepatitis C virus infection did not have a great impact on all cause mortality in the first decade of infection. Infected patients were at increased risk of dying directly from liver disease, particularly if they consumed excess alcohol, but this difference was not statistically significant.

4639. Hino K, Basuni AA, Ireland J, Newell A, Mphahlele J, Smit EJ, Ngui SL, Teo CG, Carman WF. Reappearance of hepatitis B surface antigen in immunocompromised individuals: reinfection or reactivation? Dig Dis Sci. 2002 Feb;47(2):415-8. No abstract.

4640. Idilman R, De MN, Colantoni A, Nadir A, Van T. The effect of high dose and short interval HBV vaccination in individuals with chronic hepatitis C. Am J Gastroenterol. 2002 Feb;97(2):435-9.

OBJECTIVES: The efficacy of the standard hepatitis B virus (HBV) vaccination schedule in individuals with chronic hepatitis C is reported to be reduced. Our aim was to assess the response rate to high dose, short interval HBV vaccination in such individuals. METHODS: A total of 152 individuals with chronic hepatitis C were vaccinated with 40 microg of vaccine administered monthly for 3 months. Twenty-six individuals with no evidence of liver disease underwent the same vaccination schedule and were considered to be the control group. Hepatitis C virus (HCV)-positive subjects who did not seroconvert to anti-hepatitis B surface positivity after the third dose of the vaccine (nonresponder) were vaccinated with a fourth dose of vaccine (booster dose, 80 microg). RESULTS: One hundred nine of the 152 individuals with chronic hepatitis C (72%) seroconverted to anti-hepatitis B surface positivity (> 10 mIU/ml), as compared to 24 of the 26 controls (92%, p < 0.05). Although individuals with chronic hepatitis C responded less frequently to high dose, short interval HBV vaccination than did the controls, no differences in terms of effective immunity (>100 mIU/ml) were evident among the two groups of responders (51% vs 54%). Also, no difference in response was reported between individuals with chronic active hepatitis C and controls (92% vs 80%). The response rate was significantly lower in cirrhotics than in the noncirrhotic group (54% vs 80%, p < 0.001). Besides cirrhosis, no other demographic or bioclinical factor was found to influence the response to vaccination. After the additional booster dose, the overall response was increased to 74% of the cirrhotics and 88% of the noncirrhotics. No major HBV vaccine-related adverse effects were seen. CONCLUSIONS: A high dose, short interval HBV vaccination schedule is safe in individuals with chronic hepatitis C. From these data, it is suggested that a high dose and a short interval between HBV vaccinations may produce an effective and early antibody response in such patients.

4641. Iino S. Natural history of hepatitis B and C virus infections. Oncology. 2002;62 Suppl 1:18-23. Review.

Thirty-five years have already elapsed since the discovery of hepatitis B virus (HBV), and 10 years since that of hepatitis C virus (HCV). Nonetheless, the natural history of HBV and HCV infections has not been fully defined, partly because they do not have subjective symptoms in most cases. Even when liver disease is induced by these hepatitis viruses, the clinical course is slow and mostly insidious. HBV and HCV are much alike in that they both cause a spectrum of clinical conditions ranging from the symptom-free carrier state through chronic hepatitis and liver cirrhosis to eventual hepatocellular carcinoma. Despite a close similarity, infections with HBV and HCV are very different in many aspects, from the early to end stage. Large-scale unbiased studies to sort out the natural history of HBV and HCV infections are lacking, however. Understandably, in view of the fact that only a few decades have passed since these hepatitis viruses were discovered. My personal account on the natural history of HBV and HCV infections is given here, which is based on my experience of over 40 years as a clinical and research hepatologist in Japan, although I am aware that it invites more questions than it answers.

4642. Jacobs RJ, Koff RS, Meyerhoff AS. The cost-effectiveness of vaccinating chronic hepatitis C patients against hepatitis A. Am J Gastroenterol. 2002 Feb;97(2):427-34.

OBJECTIVES: Although hepatitis A vaccination is recommended for persons with chronic liver disease, the cost-effectiveness of vaccinating patients with chronic hepatitis C virus has not been extensively studied. We evaluated its costs and benefits. METHODS: A Markov model was used to assess cost-effectiveness from the health system and societal perspectives. Costs of hepatitis A screening and vaccination were compared with savings from reduced hepatitis A treatment and work loss to determine net costs of a "screen and vaccinate" strategy. Net costs were compared with longevity gains to assess cost-effectiveness. RESULTS: Based on hypothetical cohorts of 100,000 patients, vaccination would reduce the number of hepatitis A cases 63-72%, depending on patient age. Screening and vaccination costs of $5.2 million would be partially offset by $1.5-$2.8 million reductions in hepatitis A treatment costs and $0.2-$1.0 million reductions in work loss costs. From the health system perspective, vaccination would cost $22,256, $50,391, and $102,064 per life-year saved for patients vaccinated at ages 30, 45, and 60 yr, respectively. Cost-effectiveness ratios improve when work loss prevention is considered. Results are most sensitive to hepatitis A infection and hospitalization rates, and the rate used to discount future benefits to their present values. CONCLUSIONS: Hepatitis A vaccination of chronic hepatitis C patients would substantially reduce morbidity and mortality in all age groups examined. Consistent with other medical interventions for chronic hepatitis C patients, cost-effectiveness is most favorable for younger patients.

4643. Joshi S, Cauch-Dudek K, Wanless IR, Lindor KD, Jorgensen R, Batts K, Heathcote EJ. Primary biliary cirrhosis with additional features of autoimmune hepatitis: response to therapy with ursodeoxycholic acid. Hepatology. 2002 Feb;35(2):409 13.

Patients with primary biliary cirrhosis (PBC) may have additional features of autoimmune hepatitis (AIH). Corticosteroids usually contraindicated in PBC have been advocated for these patients. Patients with antimitochondrial antibody (AMA)-positive PBC from two previous randomized, controlled trials were assessed for features of AIH. Their biochemical, immunologic, and histologic responses to ursodeoxycholic acid (UDCA) versus placebo were compared with those without AIH features. The survival of patients testing positive or negative for antinuclear antibodies (ANA) was also examined. Features of AIH were defined by the presence of 2 or more of the following: 1) alanine transaminase (ALT) > 5 x the upper limit of normal (ULN); 2) immunoglobulin G (IgG) > 2 x ULN or positive anti-smooth muscle antibody (ASMA); and 3) moderate to severe lobular inflammation on pretreatment liver biopsy. Testing for AMA, ASMA, and ANA was done by immunofluorescence. The change in serum bilirubin, alkaline phosphatase (ALP), transaminases, IgM, and IgG from baseline to 2 years was compared. Of the 331 patients randomized, 16 (4.8%) had features of AIH (12 UDCA, 4 placebo). The median percent change in serum biochemistry and immunoglobulin values were similar in patients with PBC +/- features of AIH after 2 years of therapy with UDCA. Over 2 years, little change in histologic features of AIH was observed. Survival was similar for patients with PBC with and without ANA. In conclusion, features of AIH in PBC may be transient and response to UDCA therapy similar to patients with PBC without features of AIH.

4644. Jung MC, Pape GR. Immunology of hepatitis B infection. Lancet Infect Dis. 2002 Jan;2(1):43-50. Review.

The immune response initiated by the T-cell response to viral antigens is thought to be fundamental for viral clearance and disease pathogenesis in hepatitis B virus (HBV) infection. The T-cell response during acute self-limited hepatitis B in people is characterised by a vigorous, polyclonal, and multispecific cytotoxic and helper-T-cell response. By contrast, the immune response in chronic carriers, not able to eliminate the virus, is weak or undetectable. Thus a dominant cause of viral persistence could be the existence of a weak antiviral immune response. Methodological progress in animal models allows more precise investigation of the mechanisms by which the immune system resolves viral infection or develops chronic infection. Although clearance of most virus infections is widely thought to indicate the killing of infected cells by virus-specific T cells, data suggest that non-cytolytic intracellular viral inactivation by cytokines released by virus-inactivated lymphomononuclear cells could have an important role in the clearance of this virus without killing the infected cell. Additional factors that could contribute to viral persistence, which have been partly proven in animal models, are viral inhibition of antigen processing or presentation, modulation of the response to cytotoxic mediators, immunological tolerance to viral antigens, viral mutations, and infection of immunologically privileged sites. In view of the central role of cellular immunity in disease pathogenesis, strategies have been proposed to manipulate this cellular immune response in favour of protection from disease.

4645. King MD, Reznik DA, O'Daniels CM, Larsen NM, Osterholt D, Blumberg HM. Human papillomavirus-associated oral warts among human immunodeficiency virus-seropositive patients in the era of highly active antiretroviral therapy: an emerging infection. Clin Infect Dis. 2002 Mar 1;34(5):641-8. No abstract.

4646. Lai MM. Hepatitis C virus proteins: direct link to hepatic oxidative stress, steatosis, carcinogenesis and more. Gastroenterology. 2002 Feb;122(2):568-71. Review. No abstract.

4647. Lankarani KB, Taghavi AR, Agah S, Karimi A. Comparison of intradermal and intramuscular administration of hepatitis B vaccine in neonates. Indian J Gastroenterol 2001, 20(3), 94-6. No abstract.

4648. Laskus T, Radkowski M, Wilkinson J, Vargas H, Rakela J. The origin of hepatitis C virus reinfecting transplanted livers: serum-derived versus peripheral blood mononuclear cell-derived virus. J Infect Dis. 2002 Feb 15;185(4):417-21.

When hepatitis C virus (HCV) infection recurs after liver transplantation, it is unclear whether the liver graft is colonized by virions present in the circulation or by those associated with peripheral blood mononuclear cells (PBMC). In 6 HCV-infected transplant recipients, HCV sequences were analyzed by the single-strand conformational polymorphism (SSCP) assay and direct sequencing in pretransplant-paired PBMC and serum samples and in posttransplant follow-up serum samples. In 2 patients, SSCP patterns for pretransplant PBMC-serum pairs were identical, while in 4 patients they were different. In 3 patients from the latter group, the posttransplant viral sequences resembled those found in pretransplant serum samples, whereas in the other patient from that group, viral sequences after transplantation were transiently identical to those found in pretransplant PBMC. In HCV-positive liver transplant recipients, the liver graft is colonized primarily by liver-derived virus remaining in the circulation. However, virus variants of likely extrahepatic origin can be detected in serum early after transplantation.

4649. Latorre P, Rubbia-Brandt L, Giostra E, Abid K, Negro F. The 4,977-base pair common deletion of mitochondrial DNA is not associated with steatosis in chronic hepatitis C patients. Hepatology. 2002 Jan;35(1):239-40. No abstract.

4650. Lau D. Therapy of chronic Hepatitis B. Gastroenterol Today 2000, 4(4), 172. No abstract.

4651. Lauer GM, Nguyen TN, Day CL, Robbins GK, Flynn T, McGowan K, Rosenberg ES, Lucas M, Klenerman P, Chung RT, Walker BD. Human immunodeficiency virus type 1-hepatitis C virus coinfection: intraindividual comparison of cellular immune responses against two persistent viruses. J Virol. 2002 Mar;76(6):2817-26.

Both human immunodeficiency virus type 1 (HIV-1) and hepatitis C virus (HCV) lead to chronic infection in a high percentage of persons, and an expanding epidemic of HIV-1-HCV coinfection has recently been identified. These individuals provide an opportunity for simultaneous assessment of immune responses to two viral infections associated with chronic plasma viremia. In this study we analyzed the breadth and magnitude of the CD8(+)- and CD4(+)-T-lymphocyte responses in 22 individuals infected with both HIV-1 and HCV. A CD8(+)-T-lymphocyte response against HIV-1 was readily detected in all subjects over a broad range of viral loads. In marked contrast, HCV-specific CD8(+)-T-lymphocyte responses were rarely detected, despite viral loads in plasma that were on average 1,000-fold higher. The few HCV-specific responses that were observed were relatively weak and limited in breadth. CD4-proliferative responses against HIV-1 were detected in about half of the coinfected subjects tested, but no proliferative response against any HCV protein was found in these coinfected persons. These data demonstrate a major discordance in immune responses to two persistent RNA viruses. In addition, they show a consistent and profound impairment in cellular immune responses to HCV compared to HIV-1 in HIV-1-HCV-coinfected persons.

4652. Levy S, Herve C, Delacoux E, Erlinger S. Thiamine deficiency in hepatitis C virus and alcohol-related liver diseases. Dig Dis Sci. 2002 Mar;47(3):543-8.

Thiamine deficiency is a common feature in chronic alcoholic patients, and its pathophysiology remains poorly understood. Until now, thiamine deficiency has been considered to be mainly the result of alcoholism irrespective of the underlying liver disease. The aims of the study were to compare the prevalence of thiamine deficiency in alcohol- and hepatitis C virus-(HCV-) related cirrhosis and in patients with chronic hepatitis C without cirrhosis. Forty patients with alcoholic cirrhosis (group A), 48 patients with HCV-related cirrhosis (group B), and 59 patients with chronic hepatitis C without cirrhosis (group C) were included prospectively. Thiamine status was evaluated by concomitant determination of erythrocyte transketolase activity, thiamine diphosphate (TDP) effect, and direct measurement of erythrocyte thiamine and its phosphate esters by HPLC. Thiamine was mainly present in erythrocytes in its diphosphorylated form. Prevalence of thiamine deficiency and levels of TDP in thiamine-deficient patients were similar in patients of group A (alcoholic cirrhosis) and of group B (viral C cirrhosis). None of the patients with chronic hepatitis (group C) was deficient. Thiamine deficiency was not correlated with the severity of the liver disease or disease activity. No impairment of thiamine phosphorylation was found in the three groups. conclusion, alcoholic or HCV-related cirrhotics have the same range of thiamine deficiency, while no patient without cirrhosis has thiamine deficiency, and impaired phosphorylation does not account for the deficiency observed in cirrhotics. We suggest that thiamine should be given to patients with cirrhosis irrespective of its cause.

4653. Macalalad AR, Snydman DR. GB virus C and mortality from HIV infection. N Engl J Med. 2002 Jan 31;346(5):377-9. No abstract.

4654. Madison DL, Allen E, Deodhar A, Morrison L. Henoch-Schonlein purpura: a possible complication of hepatitis C related liver cirrhosis. Ann Rheum Dis. 2002 Mar;61(3):281-2. Review. No abstract.

4655. Maguire D, Heaton ND, Smith HM. Failure of reactivation of hepatitis B after liver transplantation in hepatitis B surface antigen-negative, core antibody-positive recipients. Transplantation. 2002 Feb 15;73(3):481-2.

BACKGROUND: Hepatitis B virus (HBV) infection after liver transplantation may occur in patients previously not exposed to the virus, but who receive an organ from a surface antigen (HBsAg)-negative, core antibody (HBcAb)-positive donor. The risk of HBV reactivation after liver transplantation in recipients that are HBsAg negative and HBcAb positive requires definition, because reactivation in kidney and bone marrow transplant patients has occurred. PATIENTS AND METHODS: A total of 409 HBsAg-negative patients underwent transplantation between April 1994 and June 1999. Pretransplantation sera were tested subsequently for HbcAb and HBsAb and posttransplantation sera for HBsAg. RESULTS: Of the 55 recipients who were positive for HBcAb, 48, who were immunosuppressed predominantly using tacrolimus, showed no evidence of HBV reactivation as shown by the absence of HBsAg (mean follow up 21.3+/-13.5 months). The remaining seven died within 6 months. CONCLUSIONS: In our experience, HBV reactivation did not occur in HBsAg-negative, HBcAb-positive recipients after liver transplantation, most of whom were immunosuppressed with tacrolimus. We would not, therefore, currently recommend HBV prophylaxis in these patients.

4656. Mishra D, Singh R, Sibal A. Liver transplantation for fulminant hepatitis A infection. Indian Pediatr. 2002 Feb;39(2):189-92. No abstract.

4657. Mistry SK, Burwell TJ, Chambers RM, Rudolph-Owen L, Spaltmann F, Cook WJ, Morris SM Jr. Cloning of human agmatinase. An alternate path for polyamine synthesis induced in liver by hepatitis B virus. Am J Physiol Gastrointest Liver Physiol. 2002 Feb;282(2):G375-81. No abstract.

4658. Murrill CS, Weeks H, Castrucci BC, Weinstock HS, Bell BP, Spruill C, Gwinn M. Age-specific seroprevalence of HIV, hepatitis B virus, and hepatitis C virus infection among injection drug users admitted to drug treatment in 6 US cities. Am J Public Health. 2002 Mar;92(3):385-7.

OBJECTIVES: This study measured age-specific seroprevalence of HIV, hepatitis B virus, and hepatitis C virus (HCV) infection among injection drug users (IDUs) admitted to drug treatment programs in 6 US cities. METHODS: Remnant sera collected from persons entering treatment with a history of illicit drug injection were tested for antibodies to HIV, hepatitis C (anti-HCV), and hepatitis B core antigen (anti-HBc). RESULTS: Prevalence of anti-HBc and anti-HCV increased with age and reached 80% to 100% among older IDUs in all 6 cities. Although overall age-specific HIV prevalence was lower than anti-HCV or anti-HBc, this prevalence was greater in the Northeast than in the Midwest and West. CONCLUSIONS: The need continues for effective primary prevention programs among IDUs specifically targeting young persons who have recently started to inject drugs.

4659. Mutimer D. Positive suggestions about the anti-HBc positive donor. Gut. 2002 Jan;50(1):7-8. No abstract.

4660. Nelson DB. Effectiveness of manual cleaning and disinfection for the elimination of hepatitis C virus from GI endoscopes. Am J Gastroenterol. 2002 Jan;97(1):204-6. No abstract.

4661. Novel ring-expanded nucleoside analogs exhibit potent and selective inhibition of hepatitis B virus replication in cultured human hepatoblastoma cells. Antiviral Res. 2002 Feb;53(2):159-64. No abstract.

4662. Okuda M, Li K, Beard MR, Showalter LA, Scholle F, Lemon SM, Weinman SA. Mitochondrial injury, oxidative stress, and antioxidant gene expression are induced by hepatitis C virus core protein. Gastroenterology. 2002 Feb;122(2):366-75.

BACKGROUND & AIMS: The mechanisms of liver injury in chronic hepatitis C virus (HCV) infection are poorly understood. Indirect evidence suggests that oxidative stress and mitochondrial injury play a role. The aim of this study was to determine if the HCV core protein itself alters mitochondrial function and contributes to oxidative stress. METHODS: HCV core protein was expressed in 3 different cell lines, and reactive oxygen species (ROS) and lipid peroxidation products were measured. RESULTS: Core expression uniformly increased ROS. In 2 inducible expression systems, core protein also increased lipid peroxidation products and induced antioxidant gene expression as well. A mitochondrial electron transport inhibitor prevented the core-induced increase in ROS. A fraction of the expressed core protein localized to the mitochondria and was associated with redistribution of cytochrome c from mitochondrial to cytosolic fractions. Sensitivity to oxidative stress was also seen in HCV transgenic mice in which increased intrahepatic lipid peroxidation products occurred in response to carbon tetrachloride. CONCLUSIONS: Oxidative injury occurs as a direct result of HCV core protein expression both in vitro and in vivo and may involve a direct effect of core protein on mitochondria. These results provide new insight into the pathogenesis of hepatitis C and provide an experimental rationale for investigation of antioxidant therapy.

4663. Pandey CK, Singh N, Kumar V, Agarwal A, Singh PK. Typhoid, hepatitis E, or typhoid and hepatitis E: the cause of fulminant hepatic failure--a diagnostic dilemma. Crit Care Med. 2002 Feb;30(2):376-8.

OBJECTIVE: To report a case of hepatitis E-induced fulminant hepatic failure associated with typhoid fever, diagnosed with the Widal test. DESIGN: Case report. SETTING: Eight-bed medical/surgical intensive care unit of a university hospital. PATIENT: A 15-yr-old, 50-kg male with grade IV hepatic encephalopathy was admitted to the intensive care unit for ventilatory support. On admission to the intensive care unit he had had fever associated with loss of appetite and nausea for 15 days, jaundice for 4 days, and altered sensorium for 2 days. INTERVENTION: He was intubated and kept on elective ventilation. Tracheal aspirate, blood, urine, and stool were sterile. Anti-coma measures were instituted in the form of 20 degrees head elevation; mannitol, lactulose, and ampicillin through a nasogastric tube; and bowel wash. The mainstay of fluid therapy was 20% dextrose. Viral marker was positive for hepatitis E. He showed a favorable recovery but continued to have high-grade fever (39-40 degrees C). On investigation, peripheral blood smear was negative for malarial parasite, and Widal was positive. Fever responded to treatment with Ceftazidime. RESULT: The patient recovered with anti-coma and anti-typhoid therapy. CONCLUSION: In viral hepatitis, fever is usually present in the prodromal phase but subsides before appearance of the icteric phase. In endemic areas, if fever is present in the icteric phase of hepatitis, typhoid also should be considered in the differential diagnosis of fever, even in the absence of positive cultures for Salmonella typhi. The Widal test may be helpful in reaching a diagnosis.

4664. Pennesi M, Torre G, Del Santo M, Sonzogni A. Glomerulonephritis after recombinant hepatitis B vaccine. Pediatr Infect Dis J. 2002 Feb;21(2):172-3.

Renal complications after vaccination with hepatitis B recombinant vaccine are rare; very few cases are reported without a histopathologic definition. We describe a case of glomerulonephritis in a 12-year-old girl, beginning after the inoculation of hepatitis B vaccine. The immunohistochemical examination of her renal biopsy, with the use of monoclonal antibodies, shows the presence of hepatitis B surface antigen in renal tissue. After 2 years chronic glomerulonephritis persisted and was treated with angiotensin-converting enzyme inhibitors. After 3 years of follow-up, the renal disease was in remission, and treatment was stopped.

4665. Persico M, De Marino F, Russo GD, Morante A, Rotoli B, Torella R, De Renzo A. Efficacy of lamivudine to prevent hepatitis reactivation in hepatitis B virus-infected patients treated for non-Hodgkin lymphoma. Blood. 2002 Jan 15;99(2):724-5. No abstract.

4666. Podzorski RP. Molecular testing in the diagnosis and management of hepatitis C virus infection. Arch Pathol Lab Med. 2002 Mar;126(3):285-90. Review.

OBJECTIVES: To review hepatitis C virus (HCV), describe the types of molecular-based tests available for the diagnosis and management of HCV infection, and discuss the appropriate utilization of these tests. DATA SOURCES: Current information is presented from the published literature, as well as new information where available. STUDY SELECTION: A major cause of posttransfusion and community-acquired non-A, non-B hepatitis worldwide is HCV. Approximately 4 million people in the United States are infected with HCV, resulting in 8000 to 10,000 deaths annually. Because HCV is not readily cultured, in vitro molecular-based tests have been developed for use in the diagnosis and treatment of HCV-infected patients. Molecular tests include qualitative and quantitative nucleic acid amplification tests, branched DNA tests, and HCV genotyping assays. Qualitative HCV nucleic acid amplification tests are used routinely in association with serologic tests to help make a diagnosis of infection with HCV. Quantitative HCV testing and genotyping methods have been found to be valuable tools in the treatment of infected patients. A patient's pretreatment HCV viral load and the rate of virus decline during therapy have been shown to correlate with the likelihood of long-term response to antiviral therapy. Information pertaining to the genotype of HCV infecting patients has been shown to be helpful in making recommendations regarding treatment. Certain genotypes of HCV are much more responsive to therapy, allowing a shorter course of treatment. CONCLUSIONS: Molecular tests are valuable tools for use in the diagnosis and treatment of patients infected with HCV.

4667. Quadri R, Giostra E, Roskams T, Pawlotsky JM, Mentha G, Rubbia-Brandt L, Perrin L, Hadengue A, Negro F. Immunological and virological effects of ribavirin in hepatitis C after liver transplantation. Transplantation. 2002 Feb 15;73(3):373-8.

BACKGROUND: Hepatitis C recurring after liver transplant may cause progressive liver dysfunction, and available treatment regimens are unsatisfactory. A better understanding of the mechanisms of action of drugs currently used to manage hepatitis C would be helpful. METHODS: In a pilot, uncontrolled clinical trial, we treated 12 patients with post-liver transplantation hepatitis C with 1000-1200 mg qd of ribavirin, given as a monotherapy. We measured the transaminases levels, the liver disease grading and staging scores, the intrahepatic interferon-gamma, tumor necrosis factor-alpha, interleukin (IL)-4 and IL-10 mRNA levels, the serum and liver hepatitis C virus (HCV) RNA titers, and the intrahepatic HCV envelope 2 protein staining score before and after 12 weeks of ribavirin monotherapy. RESULTS: Ribavirin induced a significant amelioration of the transaminases levels. This biochemical response was not associated with a distinct change in the intrahepatic T helper 1/T helper 2 cytokine mRNA profile. Furthermore, some histological parameters, such as the portal inflammation and the fibrosis scores, worsened significantly even in the short term. A slight, albeit not significant, decrease of serum HCV RNA level and intrahepatic HCV antigen staining score was observed. Intrahepatic genomic-strand (but not negative-strand) HCV RNA titer decreased significantly (P=0.024). CONCLUSIONS: Contrary to what is suggested by experimental data, administration of ribavirin alone to patients with recurrent hepatitis C after liver transplantation is not accompanied by a specific change of the intrahepatic interferon-gamma, tumor necrosis factor-alpha, IL-4, or IL-10 mRNA transcription profile.

4668. Renge RL, Dani VS, Chitambar SD, Arankalle VA. Fulminant hepatitis A in children with sickle cell disease. Indian Pediatr. 2002 Feb;39(2):186-9. No abstract.

4669. Romero MA, Seoane J, Varela-Centelles P, Diz-Dios P, Otero XL. Clinical and pathological characteristics of oral lichen planus in hepatitis C-positive and negative patients. Clin Otolaryngol. 2002 Feb;27(1):22-6.

The reported prevalence rate of anti-hepatitis C virus (HCV) antibodies in patients with oral lichen planus shows wide geographical variation and ranges from 0 to 65%. Certain characteristic clinical features have been attributed to oral lichen planus associated to HCV infection. The purpose of this investigation has been to assess hypothetical clinical differences, as well as differences in the intensity of the subepithelial inflammatory infiltrate between oral lichen planus-HCV +ve patients and oral lichen planus-HCV –ve patients. A total of sixty-two patients entered the study. Their mean age was 63.5 +/- 14.49 years, and 48.4% of them were men and 51.6% women. Patients were classified according to their serum HCV positivity. Age, sex, clinical presentation (reticular or atrophic-erosive), extension of the lesions, location of the lesions, number of locations affected, intensity of the inflammatory infiltrate and Candida albicans colonization were recorded for each patient. Reticular lichen planus was the most frequent clinical presentation in both HCV +ve (57.1%) and HCV -ve patients (63.6%). C. albicans colonization ranged from 42.8% in HCV +ve and 41.7% in HCV -ve patients. HCV + ve patients showed certain oral locations more frequently affected than HCV -ve ones: lip mucosa, 28.6% versus 7.3%; tongue, 57.1% versus 29.1%; and gingiva, 71.4% versus 23.6%. The number of affected intraoral locations was higher in HCV +ve patients (71.4%) than among HCV -ve ones (20.4%; chi2 = 8.34; P < 0.011). No statistically significant differences could be established in terms of density of subepithelial inflammatory infiltrate between the groups. Our results reinforce the need for liver examination in all patients with oral lichen planus, particularly those showing lesions on the gingiva with multiple intraoral locations affected, as no pathological differences could be identified between HCV + ve and HCV -ve patients.

4670. Roque-Afonso AM, Feray C, Samuel D, Simoneau D, Roche B, Emile JF, Gigou M, Shouval D, Dussaix E. Antibodies to hepatitis B surface antigen prevent viral reactivation in recipients of liver grafts from anti-HBC positive donors. Gut. 2002 Jan;50(1):95-9.

BACKGROUND AND AIMS: Liver donors with serological evidence of resolved hepatitis B virus (HBV) infection (HBV surface antigen (HBsAg) negative, anti-HBV core (HBc) positive) can transmit HBV infection to recipients. In the context of organ shortage, we investigated the efficacy of hepatitis B immunoglobulin (HBIG) to prevent HBV infection, and assessed the infectious risk by polymerase chain reaction (PCR) testing for HBV DNA on serum and liver tissue of anti-HBc positive donors. PATIENTS: Between 1997 and 2000, 22 of 315 patients were transplanted with liver allografts from anti-HBc positive donors. Long term HBIG therapy was administered to 16 recipients. Four naive and two vaccinated patients received no prophylaxis. RESULTS: Hepatitis B developed in the four HBV naive recipients without prophylaxis and in none of the vaccinated subjects. Among the 16 recipients receiving HBIG, one patient with residual anti-HBs titres below 50 UI/ml became HBsAg positive. The remaining 15 remained HBsAg negative and HBV DNA negative by PCR testing throughout a 20 month (range 4-39) follow up period. HBV DNA was detected by PCR in 1/22 donor serum, and in 11/21 liver grafts with normal histology. A mean of 12 months post transplantation (range 1-23) HBV DNA was no longer detectable in graft biopsies from patients remaining HBsAg negative. CONCLUSION: Anti-HBs antibodies may control HBV replication in liver grafts from anti-HBc positive donors, without additional antiviral drugs. These grafts are thus suitable either to effectively vaccinated recipients or to those who are given HBIG to prevent HBV recurrence.

4671. Rosenberg PM, Farrell JJ, Abraczinskas DR, Graeme-Cook FM, Dienstag JL, Chung RT. Rapidly progressive fibrosing cholestatic hepatitis--hepatitis C virus in HIV coinfection. Am J Gastroenterol. 2002 Feb;97(2):478-83.

Fibrosing cholestatic hepatitis (FCH) is a severe and progressive form of liver dysfunction seen in organ transplant recipients infected with hepatitis B virus or hepatitis C virus (HCV) and has been attributed to cytopathic liver injury. To date, no case of FCH due to HCV has been reported in HIV-positive individuals. We describe two cases of HCV-induced FCH in two patients coinfected with HIV, culminating in rapidly progressive liver failure and death. Histological features and progression in both cases were not consistent with drug effect or obstruction. Late institution of interferon-based therapy was ultimately unsuccessful. The HCV RNA was not markedly elevated in these cases, suggesting that the cytopathic effect of HCV in these patients was not simply a consequence of viral load. FCH may in part explain the accelerated development of cirrhosis previously observed among coinfected patients. Clinicians should remain vigilant for FCH in the HIV/HCV population and consider antiviral treatment in this setting.

4672. Sarmiento OL, Ford CL, Newbern EC, Miller WC, Poole C, Kaufman JS. The importance of assessing effect modification when asserting racial differences in associations between human leukocyte antigen class II alleles and hepatitis C virus outcomes. J Infect Dis. 2002 Jan 15;185(2):266-8. No abstract.

4673. Schlaak JF, Schramm C, Radecke K, zum Buschenfelde KH, Gerken G. Sustained suppression of HCV replication and inflammatory activity after interleukin-2 therapy in patients with HIV/hepatitis C virus coinfection. J Acquir Immune Defic Syndr. 2002 Feb 1;29(2):145-8.

OBJECTIVE: There is increasing evidence that coinfection of hepatitis C (HCV) with HIV is associated with accelerated progression of liver cirrhosis. The aim of this pilot study was to investigate toxicity and efficacy of interleukin-2 (IL-2) for treatment of affected patients. DESIGN: Because low-dose, daily IL-2 therapy is well tolerated and can elevate CD4 cell counts and improve immune functions, patients were treated with 1-2 million units (MU) IL-2 subcutaneously daily. METHODS: This pilot trial included 7 HIV/HCV-coinfected individuals. During therapy, clinical, virologic, and laboratory parameters were closely monitored. RESULTS: All patients responded to IL-2 therapy with either improvement of either CD4 cell counts or liver function test results. In 2 patients, HCV-RNA in serum became negative 2 and 4 months, respectively, after cessation of therapy. HCV-RNA has remained undetectable in these 2 patients for 18 and 24 months, respectively. Therapy was well tolerated and no grade III or IV toxicities were observed. CONCLUSIONS: Low-dose, daily IL-2 therapy can improve both CD4 cell counts and liver function test results in patients with HIV/HCV coinfection and may in some cases lead to sustained suppression of viremia of HCV.

4674. Sherman KE, Rouster SD, Chung RT, Rajicic N. Hepatitis C Virus prevalence among patients infected with Human Immunodeficiency Virus: a cross-sectional analysis of the US adult AIDS Clinical Trials Group. Clin Infect Dis. 2002 Mar 15;34(6):831-7.

Hepatitis C virus (HCV) has emerged as an important etiologic agent of liver injury and failure in patients infected with human immunodeficiency virus (HIV). The prevalence and characteristics of HCV in a representative cohort of HIV-infected patients have not been described. Therefore, a representative sample of 1687 HIV-infected patients was studied; a 213-sample subcohort was selected by use of risk-based sampling from 2 large prospective US Adult AIDS Clinical Trials Group clinical trials. HCV prevalence, HCV RNA level, and genotype were determined. The weighted overall estimate of HCV prevalence in the study cohort was 16.1% (95% weighted confidence interval, 14.3%-17.8%), with significant variability depending on risk factors and HIV RNA levels. Among patients defined as being "at risk", 72.7% were HCV positive, whereas, among low-risk patients, the positivity rate was 3.5%. Genotype 1 was found in 83.3% of infected patients. Median HCV RNA level was 6.08x106 IU/mL. High virus loads and genotype 1 prevalence may be important to interferon-based antiviral response rates among coinfected patients.

4675. Shirin H, Davidovitz Y, Avni Y, Petchenko P, Krepel Z, Bruck R, Meytes D. Prevalence of hepatitis C virus infection in patients with lymphoproliferative disorders. Isr Med Assoc J. 2002 Jan;4(1):24-7. No abstract.

4676. Singh S K, Aggarwal A. Hepatitis B – one step ahead over AIDS. Antiseptic, Madurai 2001, 98(7), 270-5.

Abstract : Hepatitis is a very general term for an inflammation of liver due to variety of causes which may be metabolic disease, drugs, alcohol, toxins and viruses. Viral hepatitis is one of the most important global health problem, infecting hundred millions of individuals and responsible for more than a million deaths per year. 13 ref.

4677. Stein K, Rosenberg W, Wong J. Cost effectiveness of combination therapy for hepatitis C: a decision analytic model. Gut. 2002 Feb;50(2):253-8.

OBJECTIVE: To estimate the cost utility of treatment with combination therapy (ribavirin and interferon alpha) for hepatitis C compared with no treatment or monotherapy (interferon alpha) based on UK costs and clinical management. DESIGN: Decision analysis model using a Markov approach to simulate disease progression. SETTING: UK secondary care. PARTICIPANTS: Hypothetical cohort of patients with hepatitis C. MAIN OUTCOME MEASURES: Cost per quality adjusted life year (QALY) gained. RESULTS: Discounted cost per QALY for combination therapy over no treatment was 3791 pounds. Cost per QALY varied between 1646 pounds and 9170 pounds according to subgroup, with the lowest ratios being for genotype 2 or 3, women, those aged less than 40 years, and those with moderate hepatitis. The discounted cost per QALY of the combination over monotherapy was 3485 pounds. Similar findings were shown for subgroups as for the comparison with no treatment. One way sensitivity analysis showed that while drug costs were more important in the analysis than assumptions about disease progression or costs of treating hepatitis C disease, the results were robust to large changes in underlying assumptions. CONCLUSIONS: Combination therapy for hepatitis C is a cost effective treatment option and is superior to monotherapy. Considerable uncertainties remain over the appropriate management strategies in the populations excluded from randomised controlled trials and in whom treatment is currently being considered in the UK.

4678. Sulkowski MS, Thomas DL, Mehta SH, Chaisson RE, Moore RD. Hepatotoxicity associated with nevirapine or efavirenz-containing antiretroviral therapy: role of hepatitis C and B infections. Hepatology. 2002 Jan;35(1):182-9.

Hepatologists are frequently asked to evaluate human immunodeficiency virus (HIV)-infected patients with abnormal liver enzymes and to assess the causal role of medications, such as antiretroviral drugs. Recently, the use of HIV-1 specific non-nucleoside reverse transcriptase inhibitors (NNRTIs), including nevirapine (NVP) and efavirenz (EFV), has been associated with severe hepatic injury. We prospectively studied the incidence of severe hepatotoxicity (grade 3 or 4 change in alanine or aspartate transaminase levels) among 568 patients receiving NNRTI-containing antiretroviral therapy, including 312 and 256 patients prescribed EFV and NVP, respectively. Hepatitis C virus (HCV) and hepatitis B virus (HBV) were detected in 43% and 7.7% of patients, respectively. Severe hepatotoxicity was observed in 15.6% of patients prescribed NVP and 8.0% of those prescribed EFV, but only 32% of NVP and 50% of EFV-associated episodes were detected during the first 12-weeks of therapy. The risk was significantly greater among persons with chronic viral hepatitis (69% of cases) and those prescribed concurrent protease inhibitors (PIs) (82% of cases). Nonetheless, 84% of patients with chronic HCV or HBV did not experience severe hepatotoxicity. Severe hepatotoxicity occurs throughout the course of NNRTI therapy and is more common among patients prescribed nevirapine, those coinfected with HCV or HBV, and those coadministered protease inhibitors.

4679. Thibault V, Aubron-Olivier C, Agut H, Katlama C. Primary infection with a lamivudine-resistant hepatitis B virus. AIDS. 2002 Jan 4;16(1):131-3. No abstract.

4680. Thibault V, Candotti D, Autran B, Cahour A, Agut H. Hepatitis C virus infection in long-term nonprogressor HIV-1-infected subjects. J Acquir Immune Defic Syndr. 2002 Feb 1;29(2):204-6. No abstract.

4681. Torti C, Patroni A, Tinelli C, Sleiman I, Quiros-Roldan E, Puoti M, Castelli F. Influence of hepatitis C virus coinfection on lipid abnormalities in HIV-positive patients after highly active antiretroviral therapy. J Acquir Immune Defic Syndr. 2002 Mar 1;29(3):315-7. No abstract.

4682. van Steenbergen JE, Niesters HG, Op de Coul EL, van Doornum GJ, Osterhaus AD, Leentvaar-Kuijpers A, Coutinho RA, van den Hoek JA. Molecular epidemiology of hepatitis B virus in Amsterdam 1992-1997. J Med Virol. 2002 Feb;66(2):159-65. No abstract.

4683. Vardas E, Ross MH, Sharp G, McAnerney J, Sim J. Viral hepatitis in South African healthcare workers at increased risk of occupational exposure to blood-borne viruses. J Hosp Infect. 2002 Jan;50(1):6-12.

The prevalence of hepatitis A, B and C antibodies was measured in a group of healthcare workers (HCWs) at increased risk of occupational acquisition of blood-borne viruses (N=402) from a large, urban referral hospital in South Africa. The aims of this study were to determine the immunity of HCWs to these agents and to recommend policy for the protection of HCWs against occupational exposure to viral hepatitis in this country. Race, sex and age were shown to be important factors influencing the presence of hepatitis A (HAV) antibodies. Most black HCWs (96.2%) are protected from HAV infection. Females have significantly higher HAV antibodies compared with males and antibodies increase with increasing age. Hepatitis B antibodies (anti-HBs) were found in 30.6% of HCWs. Anti-HBs levels were significantly associated with a past history of HBV vaccination. However, only a small proportion of HCWs (21.2%) could remember ever being immunized against HBV. For those individuals that did receive HBV vaccination (N=83), the mean number of years since their last vaccine was 6.2 years (SD +/- 3.5). HCV antibodies were found in 1.8% of HCWs at increased risk of occupational exposure. It was not possible to define whether these infections were occupationally acquired but genotyping of the HCV (in two of seven cases) showed genotype 5, the predominant South African genotype. New recommendations for the prevention of viral hepatitis in HCWs in South Africa are made, including pre-employment screening for HAV based on self-selection criteria, universal anti-HBs screening with HBV booster vaccination. HCV recommendations are based on appropriate education of HCWs about this infection and its prevention and a standardized post-exposure testing protocol. Copyright 2001 The Hospital Infection Society.

4684. Vargas HE, Dodson FS, Rakela J. A concise update on the status of liver transplantation for hepatitis B virus: the challenges in 2002. Liver Transpl. 2002 Jan;8(1):2-9. Review. No abstract.

4685. Vertuani S, Bazzaro M, Gualandi G, Micheletti F, Marastoni M, Fortini C, Canella A, Marino M, Tomatis R, Traniello S, Gavioli R. Effect of interferon-alpha therapy on epitope-specific cytotoxic T lymphocyte responses in hepatitis C virus-infected individuals. Eur J Immunol. 2002 Jan;32(1):144-54. No abstract.

4686. Vohra P. Chronic viral hepatitis and its management in children. Paediat Today 2001, 4(2), 70-80.JBT. No abstract.

4687. Waris G, Siddiqui A. Interaction between STAT-3 and HNF-3 leads to the activation of liver-specific hepatitis B virus enhancer 1 function. J Virol. 2002 Mar;76(6):2721-9.

The signal transducer and activator of transcription 3 (STAT-3), a member of the STAT family of proteins, binds to a large number of transcriptional control elements and regulates gene expression in response to cytokines. While it binds to its cognate nucleotide sequences, it has been recently shown to directly interact with other transcriptional factors in the absence of DNA. We report here one such novel interaction between STAT-3 and hepatocyte nuclear factor 3 (HNF-3) in the absence of DNA. We have identified a STAT-3 binding site within the core domain of hepatitis B virus (HBV) enhancer 1. The HBV enhancer 1 DNA-STAT-3 protein interaction is shown to be stimulated by interleukin-6 (IL-6) and epidermal growth factor, which leads to an overall stimulation of HBV enhancer 1 function and viral gene expression. Using mobility shift assays and transient transfection schemes, we demonstrate a cooperative interaction between HNF-3 and STAT-3 in mediating the cytokine-mediated HBV enhancer function. Cytokine stimulation of HBV gene expression represents an important regulatory scheme of direct relevance to liver disease pathogenesis associated with HBV infection.

4688. Zylberberg H, Nalpas B, Carnot F, Skhiri H, Fontaine H, Legendre C, Kreis H, Brechot C, Pol S. Severe evolution of chronic hepatitis C in renal transplantation: a case control study. Nephrol Dial Transplant. 2002 Jan;17(1):129-33. No abstract.

Oct 2002

5354. Ali G, Kumar M, Bali SK, Wadhwa WB, Hepatitis E associated immune thrombocytopaenia and membranous glomerulonephritis. Indian J Nephrol. 2001; 11(2), 70-2.
Hepatitis E is endemic in India. Acute liver cell failure is common in Hepatitis E particularly during pregnancy. Hepatitis B and C cause various extrahepatic manifestations. Describes a case of hepatitis E who developed severe thrombocytopenia and membranous glomerulonephritis. This complication of hepatitis E has not been reported so far.

5355. Anselmo DM, Ghobrial RM, Jung LC, Weaver M, Cao C, Saab S, Kunder G, Chen PW, Farmer DG, Yersiz H, Baquerizo A, Geevarghese S, Han SH, Goldstein L, Holt CD, Gornbein JA, Busuttil RW. New era of liver transplantation for hepatitis B: a 17-year single-center experience. Ann Surg. 2002 May;235(5):611-9; discussion 619-20.

OBJECTIVE: To evaluate the variables affecting orthotopic liver transplantation (OLT) outcome for hepatitis B virus (HBV) in a large patient cohort over a 17-year period. SUMMARY BACKGROUND DATA: Historically, OLT for chronic HBV infection has been associated with aggressive reinfection and poor survival results. More recently, OLT outcome has been improved with the routine use of antiviral therapy with either hepatitis B immune globulin (HBIg) or lamivudine; however, HBV recurrence remains common. The authors studied the factors affecting HBV recurrence and outcome of transplantation, including the effects of combination viral prophylaxis with HBIg and lamivudine. METHODS: A retrospective review of 166 OLT recipients for chronic HBV over a 17-year period at a single center was performed. Median follow-up was 29 months. HBV recurrence was defined by HBsAg seropositivity after OLT. HBIg monotherapy was used in 28 (17%) patients, lamivudine monotherapy in 20 (12%), and HBIg and lamivudine combination in 89 (54%); 29 (17%) did not receive any HBV prophylaxis. Hepatocellular carcinoma (HCC) was present in 43 patients (26%) and urgent United Network for Organ Sharing (UNOS) status was assigned to 27 patients (16%). Univariate and multivariate analyses were performed to identify factors that affected OLT outcome. RESULTS: Overall 1-, 3-, and 5-year patient survival rates were 85.8%, 73.6%, and 71.8%, respectively. As expected, HBV recurrence-free survival rates were significantly lower than overall survival rates (76.4%, 58.7%, and 48.3%). When compared with a nontreated cohort, OLT recipients receiving combination viral prophylaxis with HBIg and lamivudine showed markedly reduced HBV recurrence rates and significantly improved 1- and 3-year recurrence-free survival rates. By univariate estimates, patient survival was reduced in the presence of HCC, in the Asian population, and urgent candidates by UNOS classification. Graft loss rates were significantly increased in urgent OLT candidates, Asians, patients with pretransplant positive DNA, and in the presence of HCC. Factors that were significant by univariate analysis or thought to be clinically relevant were subjected to multivariate analysis. By multivariate estimates, urgent UNOS or presence of HCC adversely affected patient and graft survival rates, whereas combination prophylactic therapy strongly predicted improved patient and graft survival rates as well as recurrence-free survival rates. CONCLUSIONS: Orthotopic liver transplantation for HBV under combination viral prophylaxis results in survival rates equivalent to other indications. Pretransplant viral replication, UNOS status, and the presence of HCC are all sensitive markers for posttransplantation outcome. Viral prophylactic therapy has effectively reduced HBV recurrence and prolonged survival outcomes. The combination of HBIg and lamivudine is the prophylactic regimen of choice.

5356. Armstrong GL, Bell BP. Hepatitis A virus infections in the United States: model-based estimates and implications for childhood immunization. Pediatrics. 2002 May;109(5):839-45.

OBJECTIVE: The high prevalence of antibody to hepatitis A virus (HAV) in the US population suggests that the incidence of infection is much higher than reported, but the infection rate is difficult to measure directly because of anicteric infection and underreporting. We present a model that reconciles the reported incidence of hepatitis A with the observed prevalence of antibody to HAV and provides an estimate of the true incidence of HAV infection. METHODS: In the model, reported incidence of hepatitis A in the United States was adjusted to account first for anicteric infection and then for underreporting and declining incidence over time such that the prevalence predicted by the model approximated that observed in 2 nationwide surveys. RESULTS: The model showed incidence in the susceptible population declining by 4.5% per year. As incidence declined early in the 1900s, the average age at infection increased, leading to a paradoxical increase in the incidence of icteric infection followed by a slow decline. The model estimated approximately 270 000 (range: 190 000-360 000) infections annually from 1980 to 1999, 10.4 times the number of hepatitis A cases actually reported during this period. More than half of these infections occurred in children who were younger than 10 years, most of which would have been clinically unrecognizable as hepatitis. CONCLUSIONS: These results suggest a large reservoir of infection in children and that interruption of transmission in children may substantially reduce incidence of hepatitis A overall.

5357. Arthur MJ. Reversibility of liver fibrosis and cirrhosis following treatment for hepatitis C. Gastroenterology. 2002 May;122(5):1525-8. No abstract.

5358. Bhaskara Rao PVR. Hepatitis-B vaccineall don’t need it. Homeopathic Prestige. 2001; 17(8), 369-74. No abstract.

5359. Carpenter PA, Huang ML, McDonald GB. Activation of occult hepatitis B from a seronegative patient after hematopoietic cell transplant: a cautionary tale. Blood. 2002 Jun 1;99(11):4245-6. No abstract.

5360. Chandra s, Gupta CP. Antibacterial activity of medicinal plant Crateava nurvala (bark) against bacterial strains causing urinary tract infection. Asian J chem. 2001; 13(3), 1181-6.
Bacterial strains EC1, KL1 and PS1 used in the study were isolated from patient’s urine, suffering from urinary tract infection (U.T.I.) and were characterized as E.coli, Klebsiella sp. and Pseudomonas sp. respectively. Antibacterial activities in crude extract of bark Crateava nurvala (varuna) plant were tested against bacterial strains in vitro. The maximum growth inhibition by the crude extract was recorded against E. coli followed by Pseudomonas sp. and Klebsiella sp. after 48 h incubation at 28 ±1⁰C being of 35.3 mm, 28.4 mm and 18.6 mm diameter respectively. As far as antibiotic sensitivity was concerned E. coli was maximum inhibited by amikacin, Klebsiella sp. and Pseudomonas sp. by ciprpfloxacin, inhibition zone being 38.1 mm, 40.5 mm and 27.2 mm respectively after 24h at 28±1⁰ C.

5361. Chatterjee C, Mitra K, Hazra SC, Banerjee D, Guha SK, Neogi DK. Prevention of HCV infection among patient of chronic active hepatitis and cirrhosis cases in Calcutta. Indian J Med Microbiol. 2001; 19(1), 46-7. No abstract.

5362. Chern JP, Lin KH. Hypoparathyroidism in transfusion-dependent patients with beta-thalassemia. J Pediatr Hematol Oncol. 2002 May;24(4):291-3.

PURPOSE: To determine the prevalence of hypoparathyroidism in transfusion-dependent patients with beta-thalassemia. PATIENTS AND METHODS: A total of 28 transfusion-dependent patients with beta-thalassemia were interviewed, and their serum calcium, phosphate, magnesium, and intact parathyroid hormone levels were checked. Serum ferritin levels were measured to monitor the effect of chelation therapy. Blood urea nitrogen, creatinine, total protein, and albumin were measured in patients with undetectable or low intact parathyroid hormone levels. RESULTS: The prevalence of hypoparathyroidism was 10.7% (3/28). Mean age at diagnosis was 18 years. The serum ferritin levels of patients with hypoparathyroidism were 1,032, 2,102, and 7,680 microg/L. Only one patient had clinical symptoms of hypocalcemia. All three of the patients with hypoparathyroidism had hypogonadism, and 66.7% (2/3) of the patients had insulin-dependent diabetes mellitus. CONCLUSIONS: Hypoparathyroidism in transfusion-dependent patients with beta-thalassemia seems to be accompanied by other endocrinopathies. Serum ferritin may not have been a reliable indicator of iron overload in the three patients with hypoparathyroidism. Severe iron overload would easily explain these multiple endocrinopathies. This pattern is commonly seen in iron-overloaded patients with thalassemia elsewhere.

5363. Chu CJ, Lok AS. Clinical significance of hepatitis B virus genotypes. Hepatology. 2002 May;35(5):1274-6. Review. No abstract.

5364. Day CP. Non-alcoholic steatohepatitis (NASH): where are we now and where are we going? Gut. 2002 May;50(5):585-8. Review.

Although non-alcoholic steatohepatitis (NASH) was considered relatively uncommon prior to the middle of the last decade, over the past three years there has been an explosion of studies on various aspects of NASH with one study reporting that after hepatitis C, NASH was the most common diagnosis in patients presenting largely with persistent abnormalities of liver function tests. The field of NASH has come a long way in a relatively short space of time. This article considers advances in knowledge that have arisen as a result of these studies and highlights areas for further work.

5365. Desai D, Aligetti M. Hepatitis G. Indian J Occup Hlth. 2001; 44(1), 30-1. No abstract.

5366. Dutta AK. IAP hepatitis B immunization schedule. Indian Pediat. 2001; 38(11), 1335-8. No abstract.

5367. Elliott JH, Kunze M, Torresi J. Hepatitis A vaccine failure. Lancet. 2002 Jun 1;359(9321):1948-9. No abstract.

5368. El-Serag HB, Everhart JE. Diabetes increases the risk of acute hepatic failure. Gastroenterology. 2002 Jun;122(7):1822-8.

BACKGROUND & AIMS: It is unclear whether patients with diabetes are at an increased risk of developing acute liver failure (ALF). We performed a large cohort study to examine the occurrence of ALF by using the databases of the Department of Veterans Affairs. METHODS: We identified all patients with a hospital discharge diagnosis of diabetes (ICD-9 codes: 250 [1-9][0-4]) from 1985 to 1990 and randomly assigned patients without diabetes for comparison (3:1 ratio). We excluded patients with concomitant liver disease as far back as 1980. After excluding the first year of follow-up, the remaining patients were observed through 2000 for the occurrence of ALF (ICD-9 570). The cumulative risk and the relative risk of ALF were determined by Kaplan-Meier and Cox Proportional Hazard survival analysis, respectively. RESULTS: We included 173,643 patients with diabetes and 650,620 patients without diabetes. Patients with diabetes were significantly older (62 vs. 54 years) and were less likely to be white (28% vs. 24%). The cumulative risk of ALF was significantly higher among patients with diabetes (incidence rate, 2.31 per 10,000 vs. 1.44 per 10,000 person-years; P < 0.0001). In the Cox proportional hazard model, diabetes was associated with a relative risk of 1.44 (95% CI, 1.26-1.63; P < 0.0001) for ALF while controlling for comorbidity index, age, sex, ethnicity, and period of service. This risk remained significantly increased after excluding patients with liver disease or viral hepatitis recorded during follow-up or those with ALF recorded after the introduction of troglitazone (relative risk = 1.40; P <0.0001). CONCLUSIONS: Diabetes increases the risk of ALF. The increase in ALF is independent of recognized underlying chronic liver disease or viral hepatitis.

5369. Enomoto M, Nishiguchi S. SEN viruses and treatment response in chronic hepatitis C virus. Lancet. 2002 May 18;359(9319):1780-1. No abstract.

5370. Feitelson MA, Sun B, Satiroglu Tufan NL, Liu J, Pan J, Lian Z. Genetic mechanisms of hepatocarcinogenesis. Oncogene. 2002 Apr 11;21(16):2593-604. Review.

The development of hepatocellular carcinoma (HCC) is a multistep process associated with changes in host gene expression, some of which correlate with the appearance and progression of tumor. Preneoplastic changes in gene expression result from altered DNA methylation, the actions of hepatitis B and C viruses, and point mutations or loss of heterozygosity (LOH) in selected cellular genes. Tumor progression is characterized by LOH involving tumor suppressor genes on many chromosomes and by gene amplification of selected oncogenes. The changes observed in different HCC nodules are often distinct, suggesting heterogeneity on the molecular level. These observations suggest that there are multiple, perhaps redundant negative growth regulatory pathways that protect cells against transformation. An understanding of the molecular pathogenesis of HCC may provide new markers for tumor staging, for assessment of the relative risk of tumor formation, and open new opportunities for therapeutic intervention.

5371. Golla R. Studies on efficacy of ribozymes and DNA enzymes against X gene of Hepatitis B Virus and HIV coreceptor CCR5. Department of Immunology, Jawaharlal Nehru University, New Delhi. 2001. No abstract.

5372. Grant M. Secondary persistent infection with hepatitis C virus: a challenge for adaptive immunity. Lancet. 2002 Apr 27;359(9316):1452. No abstract.

5373. Guido M, Fagiuoli S, Tessari G, Burra P, Leandro G, Boccagni P, Cillo U, Naccarato R, Rugge M. Histology predicts cirrhotic evolution of post transplant hepatitis C. Gut. 2002 May;50(5):697-700.

BACKGROUND: Hepatitis C recurring after orthotopic liver transplantation varies in severity and some patients rapidly develop fully established liver cirrhosis. Neither clinical nor biological markers of such rapid cirrhotic evolution are available. AIM: To assess the value of histology in identifying patients who will develop cirrhosis shortly after liver transplantation. PATIENTS AND METHODS: Only cases of recurrent hepatitis C diagnosed by both hepatitis C virus-RNA positive serum and liver changes consistent with hepatitis, with no other causes of allograft injury, were considered. A total of 128 liver biopsies were scored from 29 consecutive patients with a mean follow up of 48 (13.97) months. The histological activity index was evaluated according to Ishak et al. The time of the first histological diagnosis of recurrent hepatitis C in the absence of rejection was defined as time of histological recurrence (RHC-T). RESULTS: First histological diagnosis of recurrent hepatitis with no features of rejection was obtained at the six month biopsy in 23 of 29 cases. By the end of follow up, nine patients had developed cirrhosis (mean follow up 38 (14.39) months (range 18-60)). The remainder (mean follow up 46 (13.40) months (24-72)) showed a spectrum of fibrosis but no cirrhosis. Severe necroinflammatory lesions at RHC-T significantly correlated with rapid development of cirrhosis. At the RHC-T biopsy, only cases evolving into cirrhosis showed confluent necrosis. The median value of the histological activity index was 11 (mean 11.11 (1.76) (range 9-14)) in patients who developed cirrhosis and four (mean 4 (1.78) (range 1-8)) in the others (p<0.0001). A histological activity index > or =9 was associated with rapid development of cirrhosis in 100% of cases. CONCLUSIONS: After liver transplantation, the histological activity of recurrent hepatitis C predicts the risk of development of cirrhosis. By adopting Ishak's scoring system, a histological activity index > or =9 was 100% sensitive/specific in identifying subjects who rapidly developed cirrhosis.

5374. Guptan RC, Thakur V, Malhotra V, Sarin SK. Recombinant interferon therapy in Indian children with HBV related chronic liver disease. Indian Pediatr. 2002 May;39(5):462-7. No abstract.

5375. Heathcote EJ. Overlap of autoimmune hepatitis and primary biliary cirrhosis: an evaluation of a modified scoring system. Am J Gastroenterol. 2002 May;97(5):1090-2. No abstract.

5376. Irnich D et.al. Randomised trial of acupuncture compared with conventional massage and “sham” laser acupuncture for treatment of chronic neck pain. Selections BMJ – South Asia Edn. 2001; 17(7), 604-7. Compares the efficacy of acupuncture and conventional massage for the treatment of chronic neck pain. One week after fine treatments the acupuncture group showed a significantly greater improvement in motion related pain compared with massage (difference 24.22 (95% confidence interval 16.5 to 31.9), p=0.005)but no compared with sham laser (17.28 (10.0 to 24.6), P=0.33). Difference between acupuncture and massage of sham laser were greater in the subgroup who had pain for longer than five years (n=75) and in patients with myofascial pain syndrome (n=129). The acupuncture group had the best results in the most secondary outcome measures. There were no differences in patients’ beliefs in treatment. Acupuncture is an effective short term treatment for patients with chronic neck pain, but there is only limited evidence for long term treatments after five treatments.

5377. Jacob John T, Abraham P. Hepatitis B in India: a review of disease epidemiology. Indian Pediat. 2001; 38(11), 1318-25. No abstract.

5378. Kelly D, Skidmore S. Hepatitis C-Z: recent advances. Arch Dis Child. 2002 May;86(5):339-43. Review.

In this review, recently identified hepatitis viruses (hepatitis C, hepatitis D, hepatitis E, hepatitis F, hepatitis G, transfusion transmissible virus) are described, and the implications for paediatric liver disease discussed.

5379. Lee PC, Hung CJ, Lin YJ, Wang JR, Jan MS, Lei HY. A role for chronic parvovirus B19 infection in liver dysfunction in renal transplant recipients? Transplantation. 2002 May 27;73(10):1635-9.

BACKGROUND: Clinically, liver dysfunction in renal transplant recipients is related to hepatitis B virus (HBV) or hepatitis C virus (HCV) infection. The contribution of parvovirus B19 (B19) to liver disease in renal transplant recipients has not been studied. Here we present the association of liver dysfunction with or without the coinfection of B19, HBV, and HCV after renal transplantation. METHODS: We used enzyme-linked immunosorbent assay to identify B19, HBV, and HCV infections in serum samples taken from 144 renal transplant recipients before transplantation and at 12 and 24 months after transplantation. After each patient had fasted for 12 hr, blood was taken for measurement of aspartate aminotransferase and alanine aminotransferase monthly for at least 6 months. RESULTS: Liver dysfunction developed at the significantly higher incidence of 47% in the anti-HCV(+) patients compared with 6% in the noninfected group (P<0.0001). HBV infection had no impact on the incidence of liver dysfunction in renal transplant recipients. A higher incidence of liver dysfunction was found in 42% of B19 IgG(+)IgM(-) group patients compared with 13% of the B19 IgG(+)IgM(+) group (P=0.0051) and 9.5% of the B19 IgG(-)IgM(-) group (P=0.0003). A B19 polymerase chain reaction (PCR) assay revealed significantly higher liver dysfunction in 29% of B19 PCR(+) group patients compared with 13.6% of B19 PCR(-) patients (P=0.0419). Patients who were anti-HCV(+) and B19 PCR(+) had a significantly higher incidence of liver dysfunction than B19 PCR(-) patients (P=0.002). CONCLUSIONS: Chronic B19 infection and HCV infection, both separately and in combination, increase the incidence of liver dysfunction in renal transplant recipients. HBV infection does not seem to be independently or synergistically associated with liver dysfunction.

5380. Liaw YF. Chronic hepatitis B guidelines: east versus west. Hepatology. 2002 Apr;35(4):979-81; discussion 981-2. No abstract.

5381. Malik AS. Complications of bacteriologically confirmed typhoid fever in children. J Trop Pediatr. 2002 Apr;48(2):102-8.

To find the incidence, markers and nature of complications of typhoid fever, we studied 102 children with cultures positive for Salmonella typhi in a cross-sectional study, prospectively, over a period of almost 5 years. All isolates were sensitive to commonly used antibiotics. One third of these children developed complications which included: anicteric hepatitis, bone marrow suppression, paralytic ileus, myocarditis, psychosis, cholecystitis, osteomyelitis, peritonitis, pneumonia, haemolysis, and syndrome of inappropriate release of antidiuretic hormone (SIADH). Twelve children developed multiple complications. If hepatitis is excluded from the complications, the rate of complications in bacteriologically confirmed cases of typhoid fever drops to 11 per cent. These complications were not related to: the age or sex of patients, duration of illness before admission, use of antibiotics before admission, nutritional status, level of 'O' or 'H' titre, presence of IgM or IgG antibodies, or treatment with chloramphenicol or ampicillin. Children with splenomegaly, thrombocytopenia or leukopenia were more likely to develop complications.

5382. Miedouge M, Chatelut M, Mansuy JM, Rostaing L, Malecaze F, Sandres-Saune K, Boudet F, Puel J, Abbal M, Izopet J. Screening of blood from potential organ and cornea donors for viruses. J Med Virol 2002 Apr;66(4):571-5

Prospective nucleic acid tests were carried out for human immunodeficiency virus (HIV) and hepatitis C virus (HCV) using the COBAS Amplicor HIV-1 and HCV tests (Roche Diagnostics, Meylan, France) on potential organ (n=113) and cornea (n=368) donors in France to evaluate their performance and suitability for use as a complement to routine serological tests. Blood samples were collected from organ donors with preserved cardiac function after verification of cerebral death. Blood samples were collected from cornea donors post-mortem within 48 hr after death. An internal control was added to the samples before extraction to monitor each individual polymerase chain reaction (PCR). The nucleic acid tests were always interpretable in organ donors and negative in all except in 2 anti-HCV positive patients. One had an indeterminate HIV p24 antigen but was negative for HIV RNA. HIV and HCV RNA were not found in cornea donors with a negative serology but indeterminate molecular results were frequent in this group (17.6%). Cornea donors also gave significantly more (14.4%) indeterminate serological results than organ donors (1.8%) (P<0.001). This was due to the poor quality of the blood samples collected post-mortem. However, there was no correlation between indeterminate results of serological and molecular tests. There were 16/19 (84%) indeterminate serological results for HIV and 4/4 (100%) for HCV that were negative by PCR. Thus, nucleic acid tests could be useful for qualifying a donor whose serological results are indeterminate. The extraction procedures on post-mortem specimens and/or blood collection must be changed to improve the performance of nucleic acid tests. Copyright 2002 Wiley-Liss, Inc.

5383. Muir AJ, Rockey DC. Acute HCV: the early bird catches the virus. Gastroenterology. 2002 Apr;122(4):1176-7; discussion 1177-8. No abstract.

5384. Nafeesa F. Incidence of hepatitis C virus infection in alcoholic, post transfusion and renal transplant subjects. Department of Microbiology, Osmania University ; Hyderabad, 2001. No abstract.

5385. Pawlotsky JM. Molecular diagnosis of viral hepatitis. Gastroenterology. 2002 May;122(6):1554-68. Review.

Molecular biology-based assays are invaluable tools for the management of chronic viral hepatitis. They can be used to test blood donations, diagnose active infection, help to establish the prognosis, guide treatment decisions, and assess the virological response to therapy. This article reviews current molecular biology-based techniques and assays, and their practical use in the management of hepatitis B and C virus infection.

5386. Sanchez-Lombrana JL, Alvarez RP, Saez LR, Oliva NP, Martinez RM. Acute hepatitis associated with cetirizine intake. J Clin Gastroenterol. 2002 Apr;34(4):493-5. No abstract.

5387. Stewart DE. Hepatic adverse reactions associated with nefazodone. Can J Psychiatry. 2002 May;47(4):375-7.

OBJECTIVE: Since 1999, international reports of hepatotoxicity associated with the antidepressant nefazodone (Serzone) have increased. In June 2001, a manufacturer's safety advisory notified Canadian physicians of "very rare reports of severe liver injury temporally associated with the use of nefazodone HC1." We undertook this study to determine the prevalence of adverse drug reactions to nefazodone reported in a Canadian database. METHOD: We requested the Canadian Adverse Drug Reaction Monitoring Programme (CADRMP) database for nefazodone and analyzed it for suspected hepatic complications reported and entered from the time of marketing to June 30, 2001. RESULTS: We found 32 cases of liver injury associated with nefazodone, with 26 (81.3%) classified as "severe." Patients ranged in age from 30 to 69 years and took 100 to 600 mg of nefazodone daily. Most (68.8%) of the patients were women. Eleven patients were prescribed only nefazodone, and 20 took it concomitantly with other drugs. Of affected patients, 88% developed liver injury within 6 months of starting nefazodone. At the time of reporting, 17 patients recovered without sequelae, 12 patients had not yet recovered, and the outcomes for 3 were unknown. There were 3 cases of hepatic failure, 1 of hepatocellular degeneration, 1 of hepatic necrosis, and 1 of fulminant hepatitis. CONCLUSION: In common with similar databases, the CADRMP database includes only a small proportion of suspected drug reactions. In view of 32 reported cases of hepatotoxicity associated with nefazodone in Canada, 81.3% of which were severe, caution should be exercised if nefazodone is prescribed with other drugs, especially those metabolized by CYP4503A4. Nefazodone should not be prescribed to patients with preexisting liver disease. Baseline and regular liver function tests should be obtained in all patients on nefazodone therapy in the first 6 months, and the drug should be discontinued if abnormalities are found. Patients should be advised of symptoms of hepatotoxicity, and to report them immediately to their physician.

5388. Usuki N, Miyamoto T. Chronic hepatic disease: usefulness of serial CT examinations. J Comput Assist Tomogr. 2002 May-Jun;26(3):418-21.

PURPOSE: Our purpose was to confirm whether the progression of chronic liver disease could be determined by serial CT examinations. METHOD: We calculated the liver (right and left lobes) and spleen volumes of 34 patients with chronic liver disease, who were examined serially for >2 years using a helical CT scanner. Progression of collateral formations was also checked during follow-up. These CT findings were compared with the liver function tests by Child-Pugh score. RESULTS: The Child-Pugh score got worse in eight patients ("score-worse group") and did not change in the other patients ("score-static group"). The liver volume ratio between the first and last CT examinations was significantly smaller in the score-worse group than in the score-static group (p = 0.015). The right lobe volume ratio was also significantly smaller in the score-worse group (p = 0.009); however, the left lobe volume ratio and spleen volume ratio were not significantly different between the two groups (p = 0.656 and p = 0.365). In four patients of the score-static group, collateral formations progressed. CONCLUSION: Serial CT examinations are useful to evaluate patients with chronic liver disease. The left lobe does not become hypertrophied but tends to be preserved, in contrast to the right lobe, with the progression of the disease.

5389. Vassileva ANA. Strategies for optimisation of Hepatitis B surface antigen in Picha Pastoris. Department of Biochemistry, University of Mysore, Mysore; 2001. No abstract.

5390. Xu DZ, Yan YP, Choi BC, Xu JQ, Men K, Zhang JX, Liu ZH, Wang FS. Risk factors and mechanism of transplacental transmission of hepatitis B virus: a case-control study. J Med Virol. 2002 May;67(1):20-6.

Intrauterine hepatitis B virus (HBV) infection has been suggested to be caused by transplacental transmission that cannot be blocked by hepatitis B vaccine. This would decrease the effectiveness of hepatitis B vaccine. This study examined the risk factors and mechanism of transplacental HBV transmission. A case-control study included 402 newborn infants from 402 HBsAg-positive pregnant women. Among these, 15 newborn infants infected with HBV by intrauterine transmission were selected as cases, and the rest as controls. A pathology study included 101 full-term placentas from the HBsAg-positive pregnant women above and 14 from HBsAg-negative pregnant women. Immunohistochemistry staining and HBV DNA in situ hybridization were used to estimate the association of intrauterine HBV infection and HBV infection in the placentas. HBeAg positivity in mothers' sera (OR = 17.07, 95%CI 3.39-86.01) and threatened preterm labor (OR = 5.44, 95%CI 1.15-25.67) were found to be associated with transplacental HBV transmission. The intrauterine infection rate increased linearly and significantly with maternal serum HBsAg titers (trend test P = 0.0117) and HBV DNA concentration (trend test P < 0.01). Results of the pathology study showed that HBV infection rates decreased gradually from the maternal side to the fetal side (trend test P = 0.0009) in the placental cell layers. There was a significant association between intrauterine HBV transmission and HBV infection in villous capillary endothelial cells (VCEC) in the placenta (OR = 18.46, P = 0.0002). The main risk factors for intrauterine HBV infection are maternal serum HBeAg positivity, history of threatened preterm labor, and HBV in the placenta especially the villous capillary endothelial cells. Previous reports of transplacental leakage of maternal blood causing intrauterine infection are confirmed. In addition, there appears to be a "cellular transfer" of HBV from cell to cell in the placenta causing intrauterine infection. This latter hypothesis needs to be confirmed. Copyright 2002 Wiley-Liss, Inc.

5391. Younossi ZM, Diehl AM, Ong JP. Nonalcoholic fatty liver disease: an agenda for clinical research. Hepatology. 2002 Apr;35(4):746-52. Review. No abstract.

Pathogenesis:

5392. Campo JV, McNabb J, Perel JM, Mazariegos GV, Hasegawa SL, Reyes J. Kava-induced fulminant hepatic failure. J Am Acad Child Adolesc Psychiatry. 2002 Jun;41(6):631-2. No abstract.

5393. Carmichael M. Risking life to give life. Newsweek. 2002 Apr 22;139(16):53. No abstract.

5394. Castellote J, Gornals J, Lopez C, Xiol X. Acute tension hydrothorax: a life-threatening complication of cirrhosis. J Clin Gastroenterol. 2002 May-Jun;34(5):588-9. No abstract.

5395. Chang MH. Viral mutants and fulminant hepatitis. A dominant hepatitis B virus population defective in virus secretion because of several S-gene mutations from a patient with fulminant hepatitis. J Pediatr Gastroenterol Nutr. 2002 Apr;34(4):426. No abstract.

5396. Dieterich DT. Treatment of hepatitis C and anemia in human immunodeficiency virus-infected patients. J Infect Dis. 2002 May 15;185 Suppl 2:S128-37. Review.

Because of shared modes of transmission, co-infection with human immunodeficiency virus (HIV) and hepatitis C virus (HCV) is common. Co-infection with HIV increases HCV virus load, liver-related mortality, and the risk of sexual and perinatal transmission of HCV, and it may accelerate HCV disease progression. With combination interferon (IFN)-alpha 2b/ribavirin or pegylated IFN-alpha 2b/ribavirin therapy, long-term remission is possible for HCV-infected patients. Preliminary evidence suggests that the combination of IFN-alpha 2b/ribavirin can achieve similar response rates in HCV/HIV-co-infected individuals with no adverse effect on HIV RNA concentrations. Although adverse effects are more frequent with combination therapy than with IFN-alpha monotherapy, most are manageable. In addition, few instances of drug-drug antagonism have been reported among drugs used to treat each disease, although further study is necessary. Ribavirin-associated hemolytic anemia is a potential problem in a patient population that is already susceptible to anemia but is manageable with recombinant human erythropoietin (epoetin alfa).

5397. Dodi F, Alessandrini A, Camera M, Gaffuri L, Morandi N, Pagano G. Stevens-Johnson syndrome in HIV patients treated with nevirapine: two case reports. AIDS. 2002 May 24;16(8):1197-8. No abstract.

5398. Drago F, Rebora A. Cutaneous immunologic reactions to hepatitis B virus vaccine. Ann Intern Med. 2002 May 21;136(10):780; discussion 780-1. No abstract.

5399. El-Zayadi AR, Selim O, Hamdy H, El-Tawil A, Moustafa H. Heavy cigarette smoking induces hypoxic polycythemia (erythrocytosis) and hyperuricemia in chronic hepatitis C patients with reversal of clinical symptoms and laboratory parameters with therapeutic phlebotomy. Am J Gastroenterol. 2002 May;97(5):1264-5. No abstract.

5400. Griffiths A, Olynyk JK. Iron and the response to treatment of hepatitis C. Am J Gastroenterol. 2002 Apr;97(4):788-90. No abstract.

5401. Gupta R, Singh S, Tang R, Blackwell TA, Schiffman JS. Anterior ischemic optic neuropathy caused by interferon alpha therapy. Am J Med. 2002 Jun 1;112(8):683-4. No abstract.

5402. Hill JB, Sheffield JS, Kim MJ, Alexander JM, Sercely B, Wendel GD. Risk of hepatitis B transmission in breast-fed infants of chronic hepatitis B carriers. Obstet Gynecol. 2002 Jun;99(6):1049-52.

OBJECTIVE: To measure the rate of hepatitis B (HBV) transmission from chronic HBV carriers to breast-fed infants after immunoprophylaxis. METHODS: Since 1992, information on women with HBV during pregnancy has been collected in a prospective longitudinal study. Those HBV carriers and their infants participating in a county HBV immunoprophylaxis program were identified. Infants were followed for up to 15 months and examined for hepatitis B infection by hepatitis B surface antigen (HBsAg). RESULTS: A total of 369 infants born to women with chronic HBV met the inclusion criteria and received hepatitis B immune globulin at birth and the full course of the hepatitis B vaccine series. We compared 101 breast-fed infants with 268 formula-fed infants. There was no significant difference between the two groups with respect to the number of women who were positive for hepatitis B e antigen (HBeAg) (22% versus 26%, P =.51). Three women in the breast-feeding group had liver transaminase abnormalities, compared with six women in the formula-feeding group (P =.29). Overall, there were nine cases of HBV infection transmission (2.4%). None of the 101 breast-fed infants and nine formula-fed infants (3%) were positive for HBsAg after the initial vaccination series (P =.063). The mean length of time for breast-feeding was 4.9 months (range 2 weeks to 1 year). CONCLUSION: With appropriate immunoprophylaxis, including hepatitis B immune globulin and hepatitis B vaccine, breast-feeding of infants of chronic HBV carriers poses no additional risk for the transmission of the hepatitis B virus.

5403. Holtzman JL. The effect of alcohol on acetaminophen hepatotoxicity. Arch Intern Med. 2002 May 27;162(10):1193. No abstract.

5404. Jeantet D, Chemin I, Mandrand B, Zoulim F, Trepo C, Kay A. Characterization of two hepatitis B virus populations isolated from a hepatitis B surface antigen-negative patient. Hepatology. 2002 May;35(5):1215-24.

In a study of surface antigen-negative, but weakly hepatitis B virus (HBV) DNA-positive, patients, we were able to amplify and clone whole HBV genomes from the serum of a cirrhotic patient. Sequencing showed that the patient harbored two different HBV populations, one of genotype A and the other of genotype D, with the genotype D genome apparently predominating. The surface antigen of the genotype A virus is heavily mutated, especially in the extracellular << determinant a >> region, with several mutations that have not been previously described. The genotype D virus is a precore mutant. Both genomes possess the common A1762T-G1764A double mutation of the basal core promoter (BCP), and the genotype D virus is also mutated in the << TATA box >> of the large surface antigen promoter. Biological characterization showed that the genotype A genome was fully replication-competent, whereas the genotype D genome replicated poorly. The small surface antigen of the genotype A virus was only very weakly recognized by commercial tests. The small surface antigen of the genotype D virus could be recognized by the tests, but it was mainly retained within transfected cells, probably because of an excess of large surface antigen. In conclusion, the cryptic nature of this double HBV infection is characterized by the predominance of the replication-deficient genotype D virus over the replication-competent genotype A virus.

5405. Kawa S, Ota M, Yoshizawa K, Horiuchi A, Hamano H, Ochi Y, Nakayama K, Tokutake Y, Katsuyama Y, Saito S, Hasebe O, Kiyosawa K. HLA DRB10405-DQB10401 haplotype is associated with autoimmune pancreatitis in the Japanese population. Gastroenterology. 2002 May;122(5):1264-9.

BACKGROUND & AIMS: Autoimmune pancreatitis is a distinctive disease entity characterized by high serum immunoglobulin G4 concentrations. Because of the close association between some autoimmune diseases and particular alleles of major histocompatibility complex genes, we investigated the association between HLA alleles and autoimmune pancreatitis. METHODS: HLA-A, -B, -C, -DR, and –DQ gene typing and HLA-DRB1, -DQB1, and -DPB1 allele typing were performed by the polymerase chain reaction sequence-specific primers method and the restriction fragment length polymorphism method, respectively, in 40 patients with autoimmune pancreatitis, 43 patients with chronic calcifying pancreatitis, and 201 healthy subjects. RESULTS: In patients with autoimmune pancreatitis compared with healthy subjects, we found a significant increase in DR4 (73% vs. 44%, corrected P = 0.01) and DRB1*0405 (58% vs. 21%, corrected P = 0.000026) and DQ4 (58% vs. 26%, corrected P = 0.001) and DQB1*0401 (58% vs. 21%, corrected P = 0.000017). The DRB1*0405-DQB1*0401 haplotype in autoimmune pancreatitis showed no significant association with any HLA class I antigens, in contrast to the B54-DRB1*0405-DQB1*0401 haplotype reported in autoimmune hepatitis. The frequencies of DRB1*0405 and DQB1*0401 were significantly high in patients with autoimmune pancreatitis compared with chronic calcifying pancreatitis. CONCLUSIONS: It is probable that DRB1*0405-DQB1*0401 haplotype is associated with autoimmune pancreatitis in the Japanese population.

5406. Kazim SN, Wakil SM, Khan LA, Hasnain SE, Sarin SK. Vertical transmission of hepatitis B virus despite maternal lamivudine therapy. Lancet. 2002 Apr 27;359(9316):1488-9.

Lamivudine given during the last weeks of pregnancy in women with chronic hepatitis B has been reported to be safe. We report a case of chronic hepatitis B virus (HBV) infection in a newborn, despite suppression of HBV DNA to undetectable levels in the mother by prolonged lamivudine therapy. The newborn had raised alanine aminotransferase concentrations and was positive for HBV DNA at birth which persisted until 9 months of age, despite neonatal vaccination, treatment with hepatitis B immune globulin, and high concentrations of anti-HBs. On HBV DNA sequencing, complete sequence homology and a similar precore mutation was found in the mother and child, indicating vertical transmission. Lamivudine therapy might not prevent perinatal transmission of HBV infection in every newborn.

5407. Kladney RD, Cui X, Bulla GA, Brunt EM, Fimmel CJ. Expression of GP73, a resident Golgi membrane protein, in viral and nonviral liver disease. Hepatology. 2002 Jun;35(6):1431-40.

GP73 is a novel type II Golgi membrane protein of unknown function that is expressed in the hepatocytes of patients with adult giant-cell hepatitis (Gene 2000;249:53-65). Its expression pattern in human liver disease and the regulation of its expression in hepatocytes have not been systematically studied. The aims of the present study were to compare GP73 protein levels in viral and nonviral human liver disease and in normal livers, to identify its cellular sources, and to study the regulation of its expression in hepatoma cells in vitro. GP73 protein levels were quantitated in explant livers of patients with well-defined disease etiologies and compared with the levels in normal donor livers. GP73-expressing cells were identified immunohistochemically. GP73 expression in vitro was studied by Western blotting and immunofluorescence microscopy in HepG2 and SK-Hep-1 cells and in the HepG2-derived, hepatitis B virus (HBV)-transfected HepG2215 and HepG2T14.1 cell lines. Whole organ levels of GP73 were low in normal livers. Significant increases were found in liver disease due to viral causes (HBV, HCV) or nonviral causes (alcohol-induced liver disease, autoimmune hepatitis). In normal livers, GP73 was constitutively expressed by biliary epithelial cells but not by hepatocytes. Hepatocyte expression of GP73 was dramatically up-regulated in diseased livers, regardless of the etiology, whereas biliary epithelial cell expression did not change appreciably. GP73 was present at high levels in HepG2215 cells (a cell line that supports active HBV replication), but was absent in HepG2T14.1 cells (an HBV-transfected cell line that does not support HBV replication) and in HBV-free HepG2 cells. In SK-Hep-1 cells, GP73 expression was increased in response to interferon gamma (IFN-gamma), and inhibited by tumor necrosis factor alpha (TNF-alpha). In conclusion, increased expression of GP73 in hepatocytes appears to be a general feature of advanced liver disease, and may be regulated via distinct pathways that involve hepatotropic viruses or cytokines.

5408. Kondili LA, Chionne P, Costantino A, Villano U, Lo Noce C, Pannozzo F, Mele A, Giampaoli S, Rapicetta M. Infection rate and spontaneous seroreversion of anti-hepatitis C virus during the natural course of hepatitis C virus infection in the general population. Gut. 2002 May;50(5):693-6.

BACKGROUND: Hepatitis C virus (HCV) infection is common worldwide but there are different prevalence rates in different countries. Data on the incidence of HCV in the general population are scarce. Spontaneous viral clearance occurs in 10-25% of infected individuals after acute infection yet controversy exists regarding the frequency of spontaneous clearance during the natural course of HCV infection in the general population. AIMS: Anti-HCV prevalence, HCV infection rate, and the kinetics of anti-HCV were studied in a cross section of the general population of central Italy. STUDY POPULATION AND METHODS: Anti-HCV prevalence (EIA-3 Ortho, RIBA-3 Ortho Chiron) was estimated in 3884 randomly selected individuals. Infection rate and antibody kinetics were estimated in 2032 participants for whom a second blood sample was taken after a median follow up of seven years. HCV-RNA determination by polymerase chain reaction was performed on follow up sera. RESULTS: The overall confirmed anti-HCV prevalence was 2.4%. Two participants seroconverted for anti-HCV, giving an overall infection rate of 1.4 cases per 10 000 person years (95% confidence interval 0.2-5.2 per 10 000 person years). Of the 36 individuals confirmed as anti-HCV positive at enrollment, seven (19.4%) showed complete seroreversion. Seven (87%) of the eight individuals with indeterminate results at enrollment were serologically non-reactive at the end of follow up. Of the 25 participants confirmed to be anti-HCV positive at both enrollment and follow up, 23 (92.0%) with stable serological profiles tested positive for HCV-RNA at the end of follow up. CONCLUSIONS: There is still a permanent risk, although low, of HCV spread in the general population in an area of low level endemicity. In this setting, a wide spectrum of modifications of viral and antibody patterns can be observed in HCV infected patients.

5409. Lauret E, Rodriguez M, Gonzalez S, Linares A, Lopez-Vazquez A, Martinez-Borra J, Rodrigo L, Lopez-Larrea C. HFE gene mutations in alcoholic and virus-related cirrhotic patients with hepatocellular carcinoma. Am J Gastroenterol. 2002 Apr;97(4):1016-21.

OBJECTIVE: The increased risk of developing hepatocellular carcinoma in hereditary hemochromatosis has been associated with cirrhosis and hepatic iron overload. The aim of this study was to investigate the association between HFE gene mutations (C282Y, H63D) and hepatocellular carcinoma in patients with alcoholic and virus-related cirrhosis. METHODS: Serum markers of iron status and HFE mutations were determined in 179 patients with alcoholic cirrhosis and 98 patients with hepatitis B and/or hepatitis C virus-related cirrhosis. A total of 43 patients with alcoholic cirrhosis and 34 patients with virus-related cirrhosis had hepatocellular carcinoma. The control group consisted of 159 healthy bone marrow donors. RESULTS: No differences were found in the frequencies of mutations among patients with alcoholic cirrhosis, those with virus-related cirrhosis, and the control subjects. However, nine (20.9%) of the 43 patients with alcoholic cirrhosis and hepatocellular carcinoma were heterozygous for the C282Y mutation, compared with six (4.4%) of the 136 patients without tumor (p = 0.002). This difference was not found in patients with virus-related cirrhosis, with or without hepatocellular carcinoma, or the H63D mutation. The transferrin saturation was the only serum iron marker the value of which was significantly higher among C282Y heterozygotes with alcoholic cirrhosis compared to those without mutation. CONCLUSIONS: The high frequency of heterozygosity for the C282Y mutation in patients with alcoholic cirrhosis plus hepatocellular carcinoma suggests that the presence of this mutation could be associated with an increased risk of developing hepatocellular carcinoma in these patients.

5410. Manesis EK, Papatheodoridis GV, Hadziyannis SJ. Serum HBV-DNA levels in inactive hepatitis B virus carriers. Gastroenterology. 2002 Jun;122(7):2092-3; discussion 2093. No abstract.

5411. Mazoff CD. Re: J. Gross editorial--"Hepatitis C: a sexually transmitted disease?". Am J Gastroenterol. 2002 May;97(5):1256; discussion 1256-7. No abstract.

5412. Naoumov NV. SEN viruses and treatment response in chronic hepatitis C virus. Lancet. 2002 May 18;359(9319):1779-80; discussion 1780. No abstract.

5413. Okan V, Araz M, Aktaran S, Karsligil T, Meram I, Bayraktaroglu Z, Demirci F. Increased frequency of HCV but not HBV infection in type 2 diabetic patients in Turkey. Int J Clin Pract. 2002 Apr;56(3):175-7.

The aim of this study was to investigate the prevalence of hepatitis B and hepatitis C virus infections in type 2 diabetic patients in Gaziantep, Turkey. Six hundred and ninety-two type 2 diabetic patients and 1014 healthy blood donors were included in the study. No significant difference was found between type 2 diabetic patients and the control group for seropositivity of HBsAg (5.3% vs 5.1%, p>0.05). In contrast, anti-HCV was significantly more frequent in type 2 diabetic patients (7.5% vs 0.1%, p>0.0001). We found no significant difference for HBsAg seropositivity between type 2 diabetic patients with a disease duration of 12 months or less, but anti-HCV seropositivity was significantly more frequent in diabetic patients with a longer disease duration (p<0.05). We suggest that HCV infection is not a trigger factor for type 2 diabetes mellitus but is frequently associated with it.

5414. Okita M, Sasagawa T, Tomioka K, Hasuda K, Ota Y, Suzuki K, Watanabe A. Habitual food intake and polyunsaturated fatty acid deficiency in liver cirrhosis. Nutrition. 2002 Apr;18(4):304-8.

OBJECTIVE: We compared the habitual food intake and plasma fatty acid

composition in cirrhotic patients living in two different regions in Japan, Okayama and Toyama, and evaluated the effects of dietary polyunsaturated fatty acid and alpha-tocopherol intake on serum alanine aminotransferase (ALT) activity. METHOD: A quantitative food-frequency questionnaire method was used. RESULTS: The significantly higher intake of fish in the patients living in Toyama resulted in higher plasma levels of docosahexaenoic acid and lower levels of arachidonic acid. Serum ALT activity correlated negatively with plasma arachidonic acid (r = -0.456, P < 0.05) and alpha-tocopherol (r = -0.505, P < 0.05) levels. Dietary intakes of vitamin E and polyunsaturated fatty acids (mg/g) correlated negatively with serum ALT (r = -0.377, P < 0.05). Dietary intake of linoleic acid and the ratio of polyunsaturated to saturated fatty acid in dietary fat correlated significantly with serum ALT (r = 0.604, P < 0.01, and r = 0.622, P < 0.01, respectively). The amount of vegetable intake correlated with intake of vitamin E and polyunsaturated fatty acid (r = 0.527, P < 0.02). CONCLUSIONS: These findings suggest that habitual food intake affects the plasma fatty acid profile and that elevated serum ALT may be related to arachidonic acid deficiency and vulnerability to lipid peroxidation in cirrhotic patients with hepatitis B and C viruses.

5415. Oviedo J, Wolfe MM. Alcohol, acetaminophen, and toxic effects on the liver. Arch Intern Med. 2002 May 27;162(10):1194-5. No abstract.

5416. Patel PA, Voigt MD. Prevalence and interaction of hepatitis B and latent tuberculosis in Vietnamese immigrants to the United States. Am J Gastroenterol. 2002 May;97(5):1198-203.

OBJECTIVES: Southeast Asian immigrants, with a high prevalence of both hepatitis B and latent tuberculosis, constitute a large proportion of immigrants to the United States. Isoniazid hepatotoxicity may be associated with hepatitis B. This study was conducted to document the prevalence and interaction of hepatitis B, latent tuberculosis, and isoniazid toxicity. METHODS: Hepatitis B surface antigen (HBsAg) and tuberculin skin testing was done on 743 Vietnamese immigrants to the Midwest between January, 1991 and December, 1999. HBsAg positive cases were tested for hepatitis B e antigen (HBeAg). All tuberculin skin test-positive patients were treated with isoniazid, unless contraindicated. Complications of isoniazid treatment and compliance with hepatitis B virus immunization recommendations were evaluated. RESULTS: One hundred three subjects (13.86%) had HBsAg, and 43 (5.7%) HBeAg. Prevalences of latent tuberculosis were similar in HBsAg positive (53%) and HBsAg negative (45%) subjects. Sixty-two percent of HBeAg positive versus 19% of HBeAg negative subjects had hepatotoxic side effects requiring discontinuation of treatment (relative risk [RR] = 11.38, CI = 5.49 < RR < 23.59, p < 0.001). Three cases of severe isoniazid hepatitis occurred in 21 HBeAg positive subjects, versus no cases in 121 HBeAg negative cases treated with isoniazid (RR = 7.72, CI = 5.02 < RR < 11.88, p < 0.001). Only 58% of subjects at risk of developing hepatitis B virus infection were appropriately immunized. CONCLUSIONS: Vietnamese immigrants have a high prevalence of hepatitis B and latent tuberculosis. HBeAg positive cases have a 7.7-fold increased risk of serious isoniazid toxicity and an 11.3-fold increased risk of isoniazid side effects requiring discontinuation of treatment. HbeAg represents an important risk factor for severe isoniazid hepatitis.

5417. Radaeva S, Jaruga B, Hong F, Kim WH, Fan S, Cai H, Strom S, Liu Y, El-Assal O, Gao B. Interferon-alpha activates multiple STAT signals and down-regulates c-Met in primary human hepatocytes. Gastroenterology. 2002 Apr;122(4):1020-34.

BACKGROUND & AIMS: Interferon (IFN)-alpha therapy is currently the primary choice for viral hepatitis and a promising treatment for hepatocellular carcinoma (HCC). Primary mouse and rat hepatocytes respond poorly to IFN-alpha stimulation. Thus, it is very important to examine the IFN-alpha signal pathway in primary human hepatocytes. METHODS: The IFN-alpha-activated signals and genes in primary human hepatocytes and hepatoma cells were examined by Western blotting and microarray analyses. RESULTS: Primary human hepatocytes respond very well to IFN-alpha stimulation as shown by activation of multiple signal transducer and activator of transcription factor (STAT) 1, 2, 3, 5, and multiple genes. The differential response to IFN-alpha stimulation in primary human and mouse hepatocytes may be caused by expression of predominant functional IFN-alpha receptor 2c (IFNAR2c) in primary human hepatocytes vs. expression of predominant inhibitory IFNAR2a in mouse hepatocytes. Microarray analyses of primary human hepatocytes show that IFN-alpha up-regulates about 44 genes by over 2-fold and down-regulates about 9 genes by 50%. The up-regulated genes include a variety of antiviral and tumor suppressors/proapoptotic genes. The down-regulated genes include c-myc and c-Met, the hepatocyte growth factor (HGF) receptor. Down-regulation of c-Met is caused by IFN-alpha suppression of the c-Met promoter through down-regulation of Sp1 binding and results in attenuation of HGF-induced signals and cell proliferation. CONCLUSIONS: IFN-alpha directly targets human hepatocytes, followed by activation of multiple STATs and regulation of a wide variety of genes, which may contribute to the antiviral and antitumor activities of IFN-alpha in human liver.

5418. Redondo-Cerezo E, Nogueras-Lopez F, Martin-Vivaldi R, Simon EE. Fulminant hepatic failure as the presenting form of type 1 autoimmune hepatitis in the elderly. Am J Gastroenterol. 2002 May;97(5):1265-6. No abstract.

5419. Ross RS, Viazov S, Roggendorf M. Phylogenetic analysis indicates transmission of hepatitis C virus from an infected orthopedic surgeon to a patient. J Med Virol. 2002 Apr;66(4):461-7.

During recent years, a controversial discussion has emerged in the medical community on the real number and possible public health implications of hepatitis C virus (HCV) transmissions from infected medical staff to susceptible patients. We report here on molecular virological and epidemiological analyses involving 229 patients who underwent exposure-prone operations by an HCV-infected orthopedic surgeon. Of the 229 individuals affected, 207 could be tested. Three were positive for HCV antibodies. Molecular and epidemiological investigation revealed that two of them were not infected by the surgeon. The third patient, a 50-year-old man, underwent complicated total hip arthroplasty with trochanteric osteotomy. He harbored an HCV 2b isolate that in phylogenetic analysis of the hypervariable region 1 (HVR 1) was closely related to the HCV strain recovered from the infected surgeon, indicating that HCV-provider-to-patient transmission occurred intraoperatively. To our knowledge, this is the first documented case of HCV transmission by an orthopedic surgeon. The recorded transmission rate of 0.48% (95% confidence interval: 0.09-2.68%) was within the same range reported previously for the spread of hepatitis B virus during orthopedic procedures. Since the result of our investigation sustains the notion that patients may contract HCV from infected health-care workers during exposure-prone procedures, a series of further retrospective exercises is needed to assess more precisely the risk of HCV provider-to-patient transmission and to delineate from these studies recommendations for the guidance and management of HCV-infected medical personnel. Copyright 2002 Wiley-Liss, Inc.

5420. Ross RS, Viazov S, Thormahlen M, Bartz L, Tamm J, Rautenberg P, Roggendorf M, Deister A. Risk of hepatitis C virus transmission from an infected gynecologist to patients: results of a 7-year retrospective investigation. Arch Intern Med. 2002 Apr 8;162(7):805-10.

BACKGROUND: Currently, it is not known how often hepatitis C virus (HCV) is transmitted from infected health care workers to patients during medical care. In the present investigation, we tried to determine the rate of provider-to-patient transmission of HCV among former patients of an HCV-positive gynecologist after it was proven that he infected one of his patients with HCV during a cesarean section. METHODS: All 2907 women who had been operated on by the HCV-positive gynecologist between July 1993 and March 2000 were notified about potential exposure and were offered free counseling and testing. The crucial differentiation between HCV transmissions caused by the gynecologist and infections contracted from other sources was achieved by epidemiological investigations, nucleotide sequencing, and phylogenetic analysis. RESULTS: Of the 2907 women affected, 78.6% could be screened for markers of HCV infection. Seven of these former patients were found to have HCV. Phylogenetic analysis of HCV sequences from the gynecologist and the women did not indicate that the virus strains were linked. Therefore, no further iatrogenic HCV infections caused by the gynecologist could be detected. The resulting overall HCV transmission rate was 0.04% (1 per 2286; 95% confidence interval, 0.008%-0.25%). CONCLUSION: To our knowledge, this is the largest retrospective investigation of the risk of provider-to-patient transmission of HCV conducted so far. Our findings support the notion that such transmissions are relatively rare events and might provide a basis for future recommendations on the management of HCV-infected health care workers.

5421. Singh N, Husain S, Carrigan DR, Knox KK, Weck KE, Wagener MM, Gayowski T. Impact of human herpesvirus-6 on the frequency and severity of recurrent hepatitis C virus hepatitis in liver transplant recipients. Clin Transplant. 2002 Apr;16(2):92-6.

A role of tumor necrosis factor-alpha (TNF-alpha) In the immunopathogenesis of hepatitis C virus (HCV) infection has been proposed. The novel herpes virus, human herpes virus-6 (HHV-6), is amongst the most potent inducers of cytokines, including TNF-alpha. The impact of HHV-6 viremia on the progression of recurrent HCV hepatitis was assessed in 51 HCV-positive liver transplant recipients. The frequency of recurrent HCV hepatitis did not differ between patients with HCV viremia (47.6%, 10/21) as compared with those without HCV viremia (46.7%, 14/30, p = 0.9). However, the patients with HHV-6 viremia had a significantly higher fibrosis score upon HCV recurrence than those without HHV-6 viremia (mean 1.5 vs. 0.3, p = 0.01). An association between cytomegalovirus (CMV) viremia and HCV recurrence was not documented; 50% (15/30) of the patients with CMV viremia and 42.8% (9/21) of those without CMV viremia had recurrent HCV hepatitis (p > 0.5). Receipt of ganciclovir (administered upon the detection of CMV viremia) was associated with lower total Knodell score (mean 5.2 vs. 6.9, p = 0.05) and a trend towards lower fibrosis score (mean 0.44 vs. 1.00, p = 0.12) in patients with recurrent HCV hepatitis. Thus, HHV-6 viremia in HCV-positive liver transplant recipients identified a subgroup of patients at increased risk for early fibrosis upon HCV recurrence.

5422. Soll AH, Sees KL. Is acetaminophen really safe in alcoholic patients? Arch Intern Med. 2002 May 27;162(10):1194. No abstract.

5423. Takahashi K, Kang JH, Ohnishi S, Hino K, Mishiro S. Genetic heterogeneity of hepatitis E virus recovered from Japanese patients with acute sporadic hepatitis. J Infect Dis. 2002 May 1;185(9):1342-5. No abstract.

5424. Tazawa J, Maeda M, Nakagawa M, Ohbayashi H, Kusano F, Yamane M, Sakai Y, Suzuki K. Diabetes mellitus may be associated with hepatocarcinogenesis in patients with chronic hepatitis C. Dig Dis Sci. 2002 Apr;47(4):710-5. No abstract.

5425. Thies N. Universal neonatal immunization for Hepatitis B. J Paediatr Child Health. 2002 Apr;38(2):211; discussion 211-2. No abstract.

5426. Thorpe LE, Ouellet LJ, Hershow R, Bailey SL, Williams IT, Williamson J, Monterroso ER, Garfein RS. Risk of hepatitis C virus infection among young adult injection drug users who share injection equipment. Am J Epidemiol. 2002 Apr 1;155(7):645-53. No abstract.

5427. Tsutsumi T, Suzuki T, Shimoike T, Suzuki R, Moriya K, Shintani Y, Fujie H, Matsuura Y, Koike K, Miyamura T. Interaction of hepatitis C virus core protein with retinoid X receptor alpha modulates its transcriptional activity. Hepatology. 2002 Apr;35(4):937-46. No abstract.

5428. Volberding P, Sullivan P. Introduction: the importance of identifying and treating complications of human immunodeficiency virus disease. J Infect Dis. 2002 May 15;185 Suppl 2:S103-4. No abstract.

5429. Woitas RP, Ahlenstiel G, Iwan A, Rockstroh JK, Brackmann HH, Kupfer B, Matz B, Offergeld R, Sauerbruch T, Spengler U. Frequency of the HIV-protective CC chemokine receptor 5-Delta32/Delta32 genotype is increased in hepatitis C. Gastroenterology. 2002 Jun;122(7):1721-8. No abstract.

5430. Wong WH, Braunfeld M, Levin P. Recurrent pulmonary embolism during liver transplantation: possible role of hepatitis B immune globulin as a causative agent. Anesthesiology. 2002 May;96(5):1261-3. No abstract.

5431. Zepp F, Schuind A, Meyer C, Sanger R, Kaufhold A, Willems P. Safety and reactogenicity of a novel DTPa-HBV-IPV combined vaccine given along with commercial Hib vaccines in comparison with separate concomitant administration of DTPa, Hib, and OPV vaccines in infants. Pediatrics. 2002 Apr;109(4):e58. No abstract.

Vaccines:

5432. Barnes-Nelson N. Doctors say all newborns need Hepatitis B shot. J Natl Med Assoc. 2002 Apr;94(4):A12. No abstract.

5433. Paul Y. Hepatitis B immunization schedule recommended by IAP. Indian Pediatr. 2002 May;39(5):503-4; discussion 504-5. No abstract.

5434. Ray S, Samuel T, Hawker J, Smith S. Hepatitis B immunisation in renal units in the United Kingdom: questionnaire study. BMJ. 2002 Apr 13;324(7342):877-8. No abstract.

5435. Shiao JS, Mclaws ML, Huang KY, Guo YL. Student nurses in Taiwan at high risk for needlestick injuries. Ann Epidemiol. 2002 Apr;12(3):197-201.

PURPOSE: To describe the prevalence and characteristics of needlestick injuries (NSI) in student nurses in Taiwan. METHODS: A self-administered questionnaire was completed by 931 student nurses from 16 hospitals randomly selected from the 132 accredited hospitals. RESULTS: The questionnaire was completed by 708 of 931 students who were contacted for participation in this study. NSI during internship was reported by 61.9% (438/708) of students, of whom 14.2% (62/438) made a formal report. The majority (70.1%) of NSI occurred in the patient's room. Hollow-bored needles contributed to half (219/438) of the NSIs of which 86.8% were syringe needles. Just over half (53.2%) of those items involved in NSIs had been used on patients. Of the hollow-bored needles involved in NSIs, 21.5% had been used on a patient with an infectious disease. Vaccination against hepatitis B virus (HBV) was lacking in 47.6% of students. CONCLUSIONS: NSIs and non-reporting of NSIs were highly prevalent in nursing students. More intensive education programs should be directed at students to increase their awareness of and compliance with Universal Precautions (UP) before commencing their practical work experience. Students need to practice prompt post-exposure evaluation so that the need for early intervention can be assessed. In addition, any public health and infection control strategy should include a universal catch-up HBV vaccination program among students before commencement of internship.

Drugs :

5436. Fuller CM, Vlahov D, Ompad DC, Shah N, Arria A, Strathdee SA. High-risk behaviors associated with transition from illicit non-injection to injection drug use among adolescent and young adult drug users: a case-control study. Drug Alcohol Depend. 2002 Apr 1;66(2):189-98.

OBJECTIVE: The goal of our study was to elucidate characteristics of persons likely to transition into injection drug use so that an identifiable group with high-risk for blood-borne infection may be targeted for interventions. METHODS: An age-matched case-control analysis was performed from a cohort study in Baltimore, 1997-1999, of street-recruited non-injection and injection drug users (IDUs), aged 15-30. Cases were IDUs injecting < or = 2 years and controls were age-matched persons who used non-injection heroin, cocaine or crack. At baseline, all were interviewed about prior year-by-year behaviors; analysis using conditional logistic regression was based on information for the year prior to injection onset for the case and the same calendar time for the controls as well as recent behaviors for both groups. RESULTS: Of 270 participants, most were African American (78%), female (61%), and HIV seroprevalence was 7% at baseline. IDUs were significantly more likely than controls to be non-African American (adjusted odds ratio (AOR)=0.09) and report high school dropout (AOR=2.32), early sex-trading (AOR=2.72), and recent violence victimization (AOR=9.28). CONCLUSION: Given that new injectors are at high-risk for HIV and hepatitis yet difficult to reach for prevention efforts, our data suggest some categories to use to target non-injectors who are likely to transition into injection use.

Back to Reference