HEPATITIS
(Diagnosis, Diagnostics, Immunodiagnosis,
Immunodiagnostics, Pathogenesis, Vaccines
& Drugs)
ABSTRACTS
1254. Agarwala
S. Mitra DK. Biliary atresia--the
current management. [Review] [29 refs] Indian Journal of Pediatrics. 63(6):719-24, 1996 Nov-Dec.
Abstract
Despite extensive research, controversies still exist regarding
the etiology, pathology and management of biliary atresia. It is now thought to
be a progressive panductal inflammatory obliterative process and not a
developmental anomaly. The histologic changes are indistinguishable from
neonatal hepatitis but some changes have prognostic significance. The clinical
presentation is that of infantile obstructive cholangiopathy-waxing and waning
icterus, clay coloured stools and high coloured urine from early neonatal period.
The diagnosis is suggested by the absence of intestinal excretion on HIDA scan
and confirmed on operative
cholangiogram. Of utmost importance towards the final prognosis is early
detection, prompt confirmation and surgical treatment before 2 months of age.
Even with early treatment the result of bilioenteric drainage procedures have
been discouraging in the long term. Portoenterostomy (PE) done in older
children has been largely unsuccessful all over the world. The poor results of
PE prompted the search for alternative treatment and liver transplantation (LT)
has emerged as a viable treatment option both as a primary procedure and after
failed PE. Although the technical know-how and infrastructure are available, LT
in children has still not been done in India because of various economic
and social constraints. It is hoped
that all physicians and surgeons dealing with such patients would also consider
this treatment modality. [References:
29]
1255. Anonymous. WHO Expert Committee on Biological
Standardization. World Health Organization Technical Report Series. 889:i-vi, 1-111, 1999.
Abstract
This report presents the recommendations of a WHO Expert Committee
commissioned to coordinate activities leading to the adoption of international
requirements for the production and control of vaccines and other biologicals
and the establishment of international biological reference materials. The
report starts with a discussion of general issues brought to the Committee's
attention and provides information on the status and development of reference
materials for various antibodies, antibiotics, antigens, blood products and
related substances, cytokines and growth factors and other substances for which
the Committee has discerned a need for international reference materials. The
second part of the report, of particular relevance of manufacturers and
national control authorities, contains guidelines for the production and
control of synthetic peptide vaccines,
requirements for tick-borne encephalitis vaccine (inactivated), guidelines for
thromboplastins and plasma used to control oral anticoagulant therapy, an
amendment to the requirements for hepatitis B vaccine made by recombinant DNA
techniques and a report on the standardization and calibration of cytokine immunoassays.
1256. Arbuthnot
P. Capovilla A. Kew M. Putative role of hepatitis B virus X
protein in hepatocarcinogenesis: effects on apoptosis, DNA repair,
mitogen-activated protein kinase and JAK/STAT pathways [see comments]. [Review]
[130 refs] Journal of Gastroenterology & Hepatology. 15(4):357-68, 2000 Apr.
Abstract
Chronic infection with hepatitis B virus (HBV) is a major risk
factor for the development of hepatocellular carcinoma (HCC). The pathogenesis
of HBV-induced malignant transformation
is, however, incompletely understood. HBx, the protein encoded by the X open
reading frame, is a transcriptional activator that has been implicated in
hepatocarcinogenesis. HBx inhibits the function of the tumour suppressor
protein p53 in what is thought to be an early event in hepatocyte
transformation before the later accumulation of inactivating p53 point
mutations. HBx inhibits apoptosis but also exerts pro-apoptotic effects. The
effects of HBx on apoptosis may be important not only for the development of HCC
but also for the establishment of HBV infection. Further implication of HBx in
hepatocyte transformation has been the demonstration that it inhibits the
repair of damaged hepatocyte DNA. This effect may be mediated by interaction
with p53 or through binding to the damaged DNA binding protein (DDB), which
plays an accessory role in nucleotide excision repair. In addition, HBx
activates cell signalling cascades involving mitogen-activated protein kinase
(MAPK) and Janus family tyrosine kinases (JAK)/signal transducer and activators
of transcription (STAT) pathways. The implications of these modulating effects
of HBx are not fully understood, but they are likely to have wide-ranging
effects on hepatocyte proliferation, apoptosis and the regulation of cell growth
checkpoints. The cellular functions ascribed to HBx are unusually diverse, and
defining the biologically important role of HBx during HBV replication will go
some way to understanding the sequelae of chronic HBV infection. [References:
130]
1257.
Assy N. Minuk GY. Serum aspartate but not alanine
aminotransferase levels help to predict the histological features of chronic
hepatitis C viral infections in adults. American Journal of Gastroenterology. 95(6):1545-50, 2000 Jun.
Abstract
OBJECTIVES: The aims of this study were to assess the predictive
values of age, gender, route of transmission, extent of steatosis, alcohol
consumption, and serum aminotransferase values on the histological findings in
patients with chronic hepatitis C viral infections. METHODS: We retrospectively reviewed the charts and
liver biopsy findings from 79 adult
patients with serological evidence of chronic hepatitis C viral infections. RESULTS: The mean (+/- SD) age
of the patient population was 43.5 +/-
10.8 yr; 47 patients (60%) were male. The routes of transmission were considered to be parenteral drugs in 44
patients (56%), previous blood
transfusions in 25 (32%), and miscellaneous parenteral and nonparenteral routes in 10 (13%). The mean
histological activity core of the group
as described by Desmet et al. was 3.5 +/- 0.8 (maximum possible score, 18) and the fibrosis score 1.5 +/-0.4
(maximum possible score, 4), indicating
relatively mild disease in the majority of cases. The extent of inflammation correlated with fibrosis (r =
0.72). By multivariate stepwise
regression analyses, serum aspartate aminotransferase (AST) values
emerged as the most important
predictive variable of histological activity (r = 0.62). When overall histological activity was further divided into
portal inflammation, piecemeal
necrosis, and lobular activity, correlations were found between AST values and portal inflammation (r = 0.58) and
piecemeal necrosis (r = 0.61) but not
lobular activity (r = 0.1). A correlation was
also observed between AST values and the extent of hepatic fibrosis (r
= 0.64). On the other hand, serum ALT
values did not correlate with
histological activity but did correlate weakly with the extent of
hepatic fibrosis (r = 0.39 and 0.51,
respectively). There were no significant
correlations between age, gender, route of transmission, steatosis,
or alcohol consumption with the extent
of histological activity or fibrosis.
CONCLUSIONS: Serum AST values correlate well with two of three features
of hepatic inflammation and with the
extent of hepatic fibrosis. These
findings suggest that, among other factors, serum AST values should
be considered in decisions regarding
the need for liver biopsy and treatment in patients with chronic hepatitis C
viral infections.
1258. Bautista
AP. Impact of alcohol on the ability of Kupffer cells to produce chemokines and
its role in alcoholic liver disease. [Review] [50 refs] Journal of
Gastroenterology & Hepatology.
15(4):349-56, 2000 Apr.
Abstract
Chemokines are implicated in the pathogenesis of alcoholic liver
disease in humans and in experimental models of alcohol intoxication. The major
sources of these chemokines are Kupffer cells which represent more than 80% of
tissue macrophages in the body. Kupffer cells are highly responsive to the
effects of ethanol, endotoxin and human immunodeficiency virus (HIV)-1
glycoprotein120. These agents, either independently or in combination, may
exacerbate the production of chemokines. Chemokines are agents that are highly
chemotactic to mononuclear cells and granulocytes. The levels of these
chemokines in sera and tissue are elevated in patients with alcoholic
hepatitis, alcoholic cirrhosis, diseased livers, viral hepatitis, and in
experimental models of chronic alcohol intoxication. Alcohol-induced influx of
endotoxin from the gut into the portal
circulation is suggested to play an important role in the activation of
Kupffer cells which leads to enhanced chemokine release. The up-regulation of
chemokines during alcohol consumption is selective. During the early phase of
alcoholic liver disease, C-X-C or alpha-chemokines predominate. This is also
associated with neutrophilic infiltration of the liver. In the later stage,
up-regulation of C-C or beta-chemokine production and migration of mononuclear
cells into the liver are observed, and this may lead to liver cirrhosis.
Selective up-regulation of chemokine synthesis and release may involve
differential modulation of the transcription factors required for chemokine
gene expression. Increased cytokine release following alcohol consumption may
also regulate chemokine secretion in Kupffer cells via paracrine and autocrine
mechanisms and vice versa. In addition, infection with HIV-1 may further
compromise the liver to more damage. During HIV-1 infection, a pre-existing
liver disease superimposed on chronic alcohol consumption may also exacerbate
HIV-1 replication and lymphocytic infiltration in the liver, because of the
ability of HIV-1 gp120 to stimulate chemokine production by Kupffer cells and
stimulate migration of inflammatory
leucocytes in the liver. [References: 50]
1259. Bock
HL. Kruppenbacher JP. Bienzle U.
De Clercq NA. Hofmann F. Clemens
RL. Does the concurrent administration of an inactivated hepatitis A
vaccine influence the immune response
to other travelers vaccines?. Journal of Travel Medicine. 7(2):74-8, 2000 Mar-Apr.
Abstract
BACKGROUND: Travelers seeking protection from hepatitis A also
often need protection against other
infections, prevalent at their destinations. METHODS: A total of 396 volunteers
received not only a hepatitis A vaccine but also either a vaccine against
polio, hepatitis B, diphtheria, tetanus, yellow fever, Japanese encephalitis,
typhoid fever or rabies according to their individual needs. We investigated the
potential influence of the hepatitis A vaccination on the immune response to
the other travelers vaccines that were administered concurrently. RESULTS: With
seroprotection rates of 100% for yellow fever, Japanese encephalitis and rabies
immunization and tetanus boosters our data demonstrate that the concurrent
administration of hepatitis A vaccine does not compromise the immune response
of these vaccines. Also for oral typhoid, hepatitis B and diphtheria
vaccination we did not detect a negative influence of concurrent hepatitis A vaccine administration as compared with
respective vaccinations when given
alone. Prior to vaccination, more than one third of our subjects lacked protective antibody levels against
diphtheria and only 44% of initially seronegative travelers seroconverted to an
anti-diphtheria titer > or = 0.01 mIU/mL, supporting a need for an
additional dose. Furthermore, only two thirds of the vaccinees tested prior to
vaccination were protected against polio type 3, and the seroconversion rate
following the administration of oral polio vaccine, was lower for viral type 3
(80%), as has been previously demonstrated in settings without concurrent other
vaccinations. CONCLUSION: No negative
effect of concurrent travelers vaccinations on the immune response of
a hepatitis A vaccine has been detected
in a previous report, and, likewise our data suggest no impairment of the
antibody response of these travelers vaccines by the concurrent administration
of the hepatitis A vaccine.
1260. Calabrese
F. Pontisso P. Pettenazzo E. Benvegnu L. Vario A. Chemello
L. Alberti A. Valente M. Liver cell apoptosis in chronic
hepatitis C correlates with histological but not biochemical activity or serum
HCV-RNA levels. Hepatology.
31(5):1153-9, 2000 May.
Abstract
In hepatitis C virus (HCV) infection, mechanisms responsible for
liver cell damage are still poorly understood and both necrosis and apoptosis
may be operative. By using terminal deoxynucleotydil transferase-mediated d-UTP-biotin nick-end labeling (TUNEL) we
have evaluated and quantified apoptosis
in liver biopsy specimens from 61 patients with chronic hepatitis C. All patients had detectable
apoptotic cells in the liver. Presence
of increased apoptotic activity was confirmed in selected cases by electron microscopy and by DNA gel
electrophoresis. The amount of liver
cell apoptosis expressed as apoptotic index, ranged between 0.01% to
0.54% and showed a positive correlation
with histological activity grading (P
<.0005) and with the amount of infiltrating CD8-positive cells (P =.
01). Apoptosis did not correlate with
transaminase levels or with HCV load and
genotype. These results support the concept that immune-mediated
apoptosis may play a role in the
pathogenesis of chronic hepatitis C and indicate that this type of reaction may occur in the absence of
significant alanine transaminase (ALT)
elevation, thus explaining the lack of correlation between biochemical activity and liver histological damage.
1261. Carrigan
DR. Adenovirus infections in immunocompromised patients. [Review] [05 refs]
American Journal of Medicine.
102(3A):71-4, 1997 Mar 17.
Abstract
Adenovirus infections have been reported in as many as one-fifth
of bone marrow transplant (BMT) recipients and patients with acquired
immunodeficiency syndrome (AIDS), and in a lesser, though still prominent,
proportion of organ transplant recipients. The relative contributions of
primary infections versus reactivations from latency in immunocompromised
patients remain unclear. Compared with adult BMT recipients, pediatric BMT
recipients appear to be infected by adenovirus more frequently and earlier in
the post-transplant period. The diagnosis of adenovirus infection is
complicated by the existence of > 40 viral serotypes, although certain
subgroups are more likely to be involved in certain patient populations.
Adenoviruses are responsible for a broad range of clinical diseases that may be
associated with high mortality, including pneumonia, hepatitis, encephalitis,
hemorrhagic cystitis, and gastroenteritis. The clinical and histopathologic
features of adenovirus disease may resemble those of cytomegalovirus disease,
potentially complicating the diagnosis. Risk
factors for clinical adenovirus disease include the number of sites from
which the virus is cultured and, in BMT recipients, the presence of moderate to
severe acute graft-versus-host disease. [References: 05]
1262. Ciocca
M. Clinical course and consequences of hepatitis A infection. Vaccine.
18 Suppl 1:S71-4, 2000 Feb 18.
Abstract
Hepatitis A virus (HAV) is a small, non-enveloped RNA virus
belonging to the Picornaviridae, for which only one serotype has been
identified. Transmission is usually through the faecal-oral route by
person-to-person contact. The most common risk factors are household or sexual
contact with a sufferer, attendance or working at a day-care centre,
international travel, and association with food or waterborne outbreaks; 55% of
cases have no identifiable risk factors. HAV infection may be symptomatic or asymptomatic,
and shows three phases. Virus is shed during the incubation phase, anti-HAV IgM
appears during the symptomatic phase and can be used for diagnosis, and
anti-HAV IgG appears at the same time but persists lifelong. Unusual clinical
manifestations of hepatitis A include
cholestatic, relapsing and fulminant hepatitis. Hepatitis A accounts
for 93% of cases of acute hepatitis in
Argentina, including 7% of atypical
clinical cases. Hepatitis A is the major cause of fulminant hepatitis,
and has been reported to account for
10% of liver transplants in children in
France and 20% in Argentina. One-year survival after liver
transplantation is 64%. Prevention must
be considered as the main means of averting this severe illness.
1263. Dalekos GN.
Kistis KG. Boumba DS. Voulgari P.
Zervou EK. Drosos AA. Tsianos EV. Increased incidence of
anti-cardiolipin antibodies in patients with
hepatitis C is not associated with aetiopathogenetic link to
anti-phospholipid syndrome. European Journal of Gastroenterology &
Hepatology. 12(1):67-74, 2000 Jan.
Abstract
OBJECTIVE: Chronic infection with hepatitis C virus (HCV) has been
found to be associated with various diseases known as extra-hepatic
manifestations of HCV. Recently, HCV has been implicated as a cause of the
antiphospholipid syndrome (APLS). We conducted a study in a well-characterized
area for epidemiological and prospective studies in the north-western part of Greece in order to
address whether an aetiopathogenesis
exists between HCV and APLS. DESIGN: Seventy-five patients with chronic hepatitis C were investigated for the
presence of anti-cardiolipin antibodies
(anti-CL) and for a past medical history
supportive to the diagnosis of APLS. In addition, 24 patients with well-defined APLS (primary or secondary) and
12 patients with systemic lupus
erythematosus (SLE) were tested for the presence of markers of HCV infection (anti-HCV and HCV RNA). The SLE
patients were anti-CL-positive but none
of them had developed any of the known clinical features of APLS. In addition, 267 healthy subjects were
investigated for the presence of
anti-CL. METHODS: IgG and IgM anti-CL were determined by a quantitative isotype-specific solid phase enzyme-linked
immunosorbent assay set up in our
laboratory. Anti-HCV was determined using a third-generation enzyme immunoassay and a confirmatory
third-generation recombinant immunoblot assay. Active virus replication was
defined by the detection of HCV RNA
using a combination assay based on a reverse transcriptase polymerase chain reaction and a DNA enzyme immunoassay.
RESULTS: Of the HCV patients, 37.3% had
IgG and/or IgM anti-CL (P<0.00005 compared to healthy controls (2.25%)). However, the mean titres of each
specific isotype were significantly
lower in HCV patients compared with those found in the APLS patients (P<0.05 for IgM and P<0.001
for IgG isotypes). The mean titres of
IgG anti-CL were also significantly lower in HCV patients compared
with those found in the SLE patients
(P<0.01). All patients with APLS or SLE (n
= 36) tested negative for HCV infection markers. In addition,
neither thrombotic events nor
thrombocytopenia were associated with a positive anti-CL test in HCV patients. CONCLUSIONS: A significant
proportion of HCV patients (37.3%) had detectable
anti-CL of low titre. However, this finding was not associated with the
development of APLS. On the other hand, none of the APLS patients was positive
for HCV. Taken together, our data rather failed to reveal an aetiopathogenetic
link between HCV and APLS. For this reason, testing for HCV in patients with
APLS or follow-up for the possibility of the development of APLS in HCV
patients cannot be suggested, at least in Greek patients. More prospective
studies of longer duration are required in order to address whether HCV is
involved or not in the
aetiopathogenesis of APLS.
1264. De
Meyer S. Depla E. Maertens G.
Soumillion A. Yap SH.
Characterization of small hepatitis B surface antigen epitopes involved in binding to human annexin V. Journal of Viral
Hepatitis. 6(4):277-85, 1999 Jul.
Abstract
Previously, we have shown that small hepatitis B surface antigen
(SHBsAg) binds specifically to human annexin V (hAV) and that hAV plays a key
role in the initial steps of hepatitis B virus (HBV) infection. We have also
demonstrated the spontaneous development of anti-idiotypic antibodies
(antibodies to HBsAg Ab2) in rabbits immunized with hAV. As Ab2 is able to
inhibit the binding of hAV to SHBsAg, Ab2 might contain epitope(s) mimicking a
region of hAV for binding to SHBsAg. Identification of this epitope will
therefore reveal a SHBsAg sequence involved in hAV binding. Using a panel of
synthetic peptides covering the region of SHBsAg located on the outer surface
of the virus, binding studies showed that the region incorporating amino acids
(aa) 125-131 of SHBsAg is important for binding to Ab2 and consequently also
for binding to hAV. Further experiments
revealed that not only this region, but also the region incorporating aa
158-169, is involved in the binding of SHBsAg to hAV. As these regions are
located in the structural vicinity according to the topological model of HBsAg
proposed by Chen et al., our findings suggest that these regions are parts of a
conformational epitope of SHBsAg for binding to hAV. Because of the crucial
role of hAV in HBV infection, further studies on the HBsAg epitopes for hAV
binding may lead to the development of a new generation of vaccines or
molecules for prevention and for treatment of patients with chronic hepatitis
B.
1265. Degos
F. Christidis C. Ganne-Carrie N. Farmachidi JP. Degott C. Guettier C. Trinchet JC. Beaugrand
M. Chevret S. Hepatitis C virus related
cirrhosis: time to occurrence of hepatocellular carcinoma and death. Gut. 47(1):131-6, 2000 Jul.
Abstract
BACKGROUND: In patients with hepatitis C virus (HCV) infection and
cirrhosis, long term outcome and the incidence of hepatocellular carcinoma
(HCC) are still debated. DESIGN: From January 1987 to January 1997, 416
patients (240 male, median age 57 years) with uncomplicated Child-Pugh A HCV
related cirrhosis were followed in two Paris area centres from diagnosis of
cirrhosis until death or reference date (1 June 2024). The analysis used a
three state disability model generalising the Cox model. RESULTS: Of the 416
patients, 60 developed HCC with a five year rate of 13.4% (95% confidence
interval (CI) 9.0-17.8%) and 83 died (including 34 with HCC), with a five year
death rate of 15.3% (95% CI 12.6-18.0%). By multivariable analysis, time to HCC
relied on age (hazard ratio (HR) 1.05 per year; p=0.0005), male sex (HR 2.13;
p=0.01), oesophageal varices (HR 2.36;
p= 0.008), decreased platelet count (HR 0.99; p=0. 03), and bilirubin level (HR 1.01; p=0.003), while
death after HCC was mainly related to
tobacco consumption (HR 1.04; p=0.0006). In contrast, death free of HCC was dependent on age (HR 1.04;
p=0.01), oesophageal varices (HR 2.75; p=0.001), low platelet count (HR 0.99;
p=0.006), and albumin level (HR 0.90; p=0.0001). CONCLUSION: The incidence of
HCC and mortality should be higher in these patients than previously stated,
and prognostic factors of HCC and death are closely related age and symptoms of
portal hypertension.
1266. El
Mir S. Triebel F. A soluble lymphocyte
activation gene-3 molecule used as a vaccine adjuvant elicits greater humoral
and cellular immune responses to both particulate and soluble antigens. Journal
of Immunology. 164(11):5583-9, 2000 Jun
1.
Abstract
The lymphocyte activation gene-3 (LAG-3) product is a MHC class II
ligand that has been used in vivo to stimulate MHC class II+ APCs to increase
tumor-specific immune responses. We investigated whether LAG-3 could also play
an adjuvant role in vivo for the induction of humoral and CD4 or CD8
cell-mediated immune responses when immunizing mice with a particulate
(hepatitis B surface Ag) or soluble (OVA) Ag. In both cases, coadministration
of 1 microg of a soluble fusion protein between murine LAG-3 and the Fc
fraction of a murine IgG2a mAb (mLAG-3Ig) as a vaccine adjuvant induced or
increased CTL responses to the corresponding MHC class I-restricted peptide. In
addition, splenocytes of mice vaccinated with either the particulate or soluble
Ag plus mLAG-3Ig exhibited a
significantly greater proliferative response than did splenocytes of
mice immunized with Ag and a control Ig
molecule. Similarly, these splenocytes
had a greater Th1- but not Th2-type cytokine response. Finally, mice immunized with Ag plus mLAG-3Ig produced
higher titers of Abs than mice
immunized with Ag and a control Ig molecule. Thus, these data
provide evidence of a novel means of
improving the immunogenicity of subunit
vaccines.
1267. Fattori
D. Urbani A. Brunetti M. Ingenito
R. Pessi A. Prendergast K. Narjes
F. Matassa VG. De Francesco R. Steinkuhler C. Probing the active site of the hepatitis C virus
serine protease by fluorescence resonance energy transfer. Journal of
Biological Chemistry. 275(20):15106-13,
2000 May 19.
Abstract
A serine protease domain contained within the viral NS3 protein is
a key player in the maturational processing of the hepatitis C virus
polyprotein and a prime target for the development of antiviral drugs. In the
present work, we describe a dansylated hexapeptide inhibitor of this enzyme.
Active site occupancy by this compound could be monitored following
fluorescence resonance energy transfer between the dansyl fluorophore and
protein tryptophan residues and could be used to 1) unambiguously assess active
site binding of NS3 protease inhibitors, 2) directly determine equilibrium and
pre-steady-state parameters of enzyme-inhibitor complex formation, and 3)
dissect, using site-directed mutagenesis, the contribution of single residues
of NS3 to inhibitor binding in direct
binding assays. The assay was also used to characterize the inhibition
of the NS3 protease by its cleavage products. We show that enzyme-product
inhibitor complex formation depends on the presence of an NS4A cofactor
peptide. Equilibrium and pre-steady-state data support an ordered mechanism of
ternary (enzyme-inhibitor-cofactor) complex formation, requiring cofactor
complexation prior to inhibitor binding.
1268.
Flint M.
McKeating JA. The role of the hepatitis C virus glycoproteins in
infection. [Review] [95 refs] Reviews in Medical Virology. 10(2):101-17, 2000 Mar-Apr.
Abstract
HCV encodes two glycoproteins, E1 and E2, that are believed to be
exposed on the surface of virions. These molecules are likely to be involved
in viral interactions with the host
immune response and responsible for mediating viral entry into target cells.
They are obvious major components for prototype vaccine studies. Recently, E2
has been reported to bind to the tetraspan molecule CD81, which represents a
putative receptor for HCV. Here, we discuss the role the HCV gps may play
during infection, the contribution of E2 gp variation to HCV evasion from the
immune response and possible implications of the E2-CD81 interaction for HCV
pathogenesis. Copyright 2000 John Wiley & Sons, Ltd. [References: 95]
1269.
Greaves M.
Title
Chronic urticaria. [Review] [64 refs]
Source
Journal of Allergy & Clinical
Immunology. 105(4):664-72, 2000 Apr.
Abstract
Chronic urticaria remains a major problem in
terms of etiology,
investigation, and management. It is
important to identify patients in
whom physical urticaria is the principal
cause of disability. Once
confirmed by appropriate challenge testing,
no further investigation is
required. Urticarial vasculitis (UV) is a
major differential diagnosis of
"idiopathic" urticaria (CIU). I perform
biopsy of most patients in this
category because UV cannot be considered
confirmed in the absence of
histologic evidence. Patients with confirmed
UV need to be thoroughly
investigated for paraproteins, lupus
erythematosus hepatitis B and C, and
inflammatory bowel disease. Of patients with
CIU, a few (<5%) prove to
have food additive reactivity confirmed by
placebo-controlled challenge
testing. There is no convincing evidence of
the involvement of
Helicobacter pylori or parasite infestation
as a cause of chronic
urticaria, although H pylori could have an
indirect role. Recently it has
become clear that 27% to 50% of patients
with CIU have functional
autoantibodies directed against the
alpha-chain of the high-affinity IgE
receptor or less commonly against IgG. These
antibodies, whose involvement
has now been independently confirmed in
several centers, are identified by
autologous serum skin testing and confirmed
by histamine release studies
or immunoblotting. Their removal (by
intravenous Ig or plasmapheresis) or
treatment by cyclosporine has proved highly
beneficial in severely
affected patients. However, the routine
treatment of all CIU patients,
irrespective of etiology, remains the
judicious use of H(1)
antihistamines. [References: 64]
1270.
Hass PL.
Title
Differentiation and diagnosis of jaundice.
[Review] [29 refs]
Source
AACN Clinical Issues. 10(4):433-41, 1999 Nov.
Abstract
Bilirubin metabolism is a complex and
fascinating example of the body's
ability to discard, renew, and recycle vital
elements. Jaundice is the
warning sign for derangements in this
system. As is true of pain, jaundice
is a powerful impetus for visiting a
healthcare provider. Usually
associated with hepatitis by a nonclinician,
the origins of jaundice can
range from benign to fatally malignant.
Patients may have any number of
idiopathic or nosocomial conditions that can
contribute to an icteric
state. This review delineates the steps of
bilirubin metabolism,
enumerates the sources of bilirubin
derangement, and examines elements of
patient condition and therapeutics that can
contribute to
hyperbilirubinemia and jaundice.
[References: 29]
1271.
Haviv YS. Sharkia M.
Galun E. Safadi R.
Title
Pancreatitis following hepatitis A
vaccination.
Source
European Journal of Medical Research. 5(5):229-30, 2000 May 23.
Abstract
We describe a 23-year-old male patient who
presented with epigastric
abdominal pain, 8 days following vaccination
with inactivated hepatitis A
virus (Haverix(R)). Clinical and laboratory
data confirmed the diagnosis
of pancreatitis. Repeat polymerase chain
reaction (PCR) for hepatitis A
replication was negative. A comprehensive
evaluation ruled out other
etiologies for pancreatitis. IgM Hepatitis A
antibodies did not develop
even after 3 months. Pancreatitis following
Hepatitis A is a well-known
complication of the viremia, but the exact
mechanism is controversial. We
suggest that the pancreatitis may have been
a cellular immunlogical
reaction to one of the antigens of hepatitis A virus vaccine, or
it might
have been caused by the release of mediators
of anaphylaxis such as
histamine and leucotriens, induced by HAV
antigens, resulting in
pancreatitis without development of humoral
immunization.
1272.
Huang CJ. Chen YH.
Ting LP.
Title
Hepatitis B virus core protein interacts
with the C-terminal region of
actin-binding protein.
Source
Journal of Biomedical Science. 7(2):160-8, 2000 Mar-Apr.
Abstract
Hepatitis B viral core protein is present in
the nucleus and cytoplasm of
infected hepatocytes. There is a strong
correlation between the
intrahepatic distribution of core protein
and the viral replication state
and disease activity in patients with
chronic hepatitis. To understand the
role of core protein in the pathogenesis of
HBV, we used a yeast
two-hybrid system to search for cellular
proteins interacting with the
carboxyl terminus of core protein, as this
region is involved in a number
of important functions in the viral
replication cycle including RNA
packaging and DNA synthesis. A cDNA encoding
the extreme C-terminal region
of human actin-binding protein, ABP-276/278,
was identified. This
interaction was further confirmed both in
vitro and in vivo. In addition,
the extreme C-terminal region of ABP-276/278
interacted with the nearly
full-length HBV core protein. Since this
region is present in both the
core and the precore proteins, it is likely
that both core and precore
proteins of HBV can interact with the
C-terminal region of ABP-276/278.
The minimal region of ABP-276/278 which
interacted with the HBV core
protein was the C-terminal 199 amino acid
residues which correspond to
part of the 23rd repeat, the entire 24th
repeat and the intervening hinge
II region in ABPs. The potential functional
outcome of ABP interaction in
HBV replication and its contribution to the
pathological changes seen in
patients with chronic HBV infection are
discussed.
1273.
Kessel A. Rosner I.
Zuckerman E. Golan TD. Toubi E.
Title
Use of antikeratin antibodies to distinguish
between rheumatoid arthritis
and polyarthritis associated with hepatitis
C infection.
Source
Journal of Rheumatology. 27(3):610-2, 2000 Mar.
Abstract
OBJECTIVE: To investigate whether
antikeratin antibodies (AKA) could be
useful in the differential diagnosis of
patients with rheumatoid arthritis
(RA) compared to patients with hepatitis C
virus (HCV) associated
polyarthritis, who are seropositive for
rheumatoid factor (RF). METHODS:
AKA were assayed in 3 different groups of
patients; all were RF
seropositive: Group 1: 25 patients with HCV
associated polyarthralgia or
arthritis. Group 2: 33 patients with RA.
Group 3: 13 patients with
autoimmune disorders other than RA. Fifteen
healthy individuals served as
controls. RESULTS: AKA were detected in
20/33 patients with RA (60.6%)
compared to only 2/25 patients (8%) with HCV
associated arthritis (p <
0.0001). AKA were observed in 2/13 patients
of Group 3 (15.3%). These
results were also statistically different
from those of patients with RA
(p = 0.008). AKA were not found in the sera
of the healthy controls.
CONCLUSION: AKA is a useful marker to
differentiate patients with RA from
those with hepatitis C arthritis.
1274.
Kimura Y. Hayashida K. Ishibashi H. Niho Y. Yanagi Y.
Title
Antibody-free virion titer greatly differs
between hepatitis C virus
genotypes.
Source
Journal of Medical Virology. 61(1):37-43, 2000 May.
Abstract
Hepatitis C virus (HCV) virions have been
shown to be bound to antibodies
in patients with chronic HCV infection. The
sera from patients infected
with genotype 1b HCV contained more
antibody-free virions than those from
patients with genotype 2a/2b HCV. When
compared at the same levels of
serum HCV RNA, free virion titers of
genotype 2a/2b-infected patients were
much lower than those of genotype
1b-infected patients, indicating that a
larger fraction of HCV virions are bound to
antibodies in the former than
in the latter. The gene segments encoding
the hypervariable region (HVR)
1, a principal neutralization epitope, of
HCV were amplified from the
patients' sera by reverse
transcription-polymerase chain reaction. The
majority of genotype 2a/2b-infected patients
had very similar HVR 1
sequences to one another, whereas patients
infected with genotype 1b HCV
had highly heterogeneous sequences.
Differences in the amount of
antibody-free virion and HVR1 sequence
variability between genotypes may
have an implication in HCV pathogenesis.
Copyright 2000 Wiley-Liss, Inc.
1275.
Lakshman M. Nichter M.
Title
Contamination of medicine injection
paraphernalia used by registered
medical practitioners in south India: an
ethnographic study.
Source
Social Science & Medicine. 51(1):11-28, 2000 Jul.
Abstract
While considerable attention has been
directed at the important role of
intravenous drug use in the spread of human
immunodeficiency virus (HIV)
and hepatitis B, little research to date has
been conducted on the role of
medicine injections in disease transmission.
This is the case despite the
fact that (a) the number of medicine
injections is several orders of
magnitude greater than injections of illegal
drugs and (b) the networks of
people potentially affected by contaminated
medicine injection
paraphernalia is far wider. In this article
we examine the medicine
injecting practices of a random sample of 40
registered medical
practitioners (RMP) who have not had formal
training in allopathic
medicine (do not have MBBS or MD degrees) in Tamil Nadu, India.
Attention
is drawn to: (a) the lack of vigilance
practitioners exercise in
maintaining hygienic needles and syringes,
(b) their perceptions of what
constitutes acceptable hygienic procedure
and (c) how patients respond in
contexts where they are able to purchase
disposable needles and syringes
directly from practitioners or from the open
market prior to visiting a
practitioner. Study results are a cause for
alarm and indicate widespread
contamination of injection paraphernalia as
well as common reuse of
disposable needles. The study was confined
to RMPs and the researchers
strongly suggest that future studies of MBBS
trained doctors practising in
the public and private sectors be carried
out. A structured observation
instrument developed to record needle and
syringe contamination during the
process of injection administration is
provided.
1276.
Lakshmi G. Reddy RP.
Kumar KK. Bhavani NV. Dayanand M.
Title
Study of the safety, immunogenicity and
seroconversion of a hepatitis-B
vaccine in malnourished children of India.
Source
Vaccine.
18(19):2009-14, 2000 Apr 3.
Abstract
Sixty rural children who were seronegative
for HBV markers received three
doses of 10 microgram of a new Hepatitis-B
vaccine, Revac-B (1 ml of
vaccine contains 20 microgram recombinant
surface antigen) that was
formulated from hepatitis-B surface antigen
expressed in a recombinant
strain of Saccharomyces cerevisiae. Vaccines
were administered on a 0, 30
and 60-day schedule. Levels of anti-HBs
titres were determined on the
30th, 60th and 90th days following the
initial injection. None of the
participants in the trial had serious
adverse reactions and the
frequencies of minor side effects were
minimal. No clinically important
adverse effects which could be considered as
directly related to the
vaccination were recorded. The volunteers
showed a very good immune
response and were seroprotected on the 30th
day after the first dose of
vaccination. The present study revealed that
the new vaccine, Revac-B is
highly immunogenic and is well tolerated.
1277.
Lima AR. Lima MS.
Soares BG. Churchill R. Farrell M.
Title
Carbamazepine for cocaine dependence.
[Review] [6 refs]
Source
Cochrane Database of Systematic Reviews
[computer file]. (2):CD002023,
2000.
Abstract
BACKGROUND: Cocaine dependence has become a
substantial public health
problem, developing a significant number of
medical, psychological and
social problems, including the spread of
infectious diseases (e.g. AIDS,
hepatitis and tuberculosis), crime, violence
and neonatal drug exposure.
Although there is no consensus regarding how
to treat cocaine dependence,
effective pharmacotherapy has a potentially
major role to play as part of
a broader treatment milieu. The
anti-convulsant carbamazepine, a tricyclic
medication that is widely used to treat a
variety of neurological and
psychiatric disorder, has also been used for
treatment of cocaine
dependence, although its effectiveness has
not been established.
OBJECTIVES: To determine whether
carbamazapine (CBZ) is effective on the
treatment of cocaine dependence. SEARCH
STRATEGY: Electronic searches of
Cochrane Library, EMBASE, MEDLINE, PsycLIT,
Biological Abstracts and
LILACS; scan of reference list of relevant
articles; personal
communication; conference abstracts;
unpublished trials from
pharmaceutical industry; book chapters on
treatment of cocaine dependence.
SELECTION CRITERIA: The inclusion criteria
for all randomised controlled
trials were that they should focus on the
use of carbamazepine drugs
versus placebo on the treatment of cocaine
dependence. Trials including
patients with additional diagnosis such as
opiate dependence were also
eligible. DATA COLLECTION AND ANALYSIS: The
reviewers extracted the data
independently and Odds Ratios, weighted mean
difference and number needed
to treat were estimated. Qualitative
assessments of the methodology of
eligible studies were carried out using
validated checklists. The
reviewers assumed that people who died or
dropped out had no improvement
and tested the sensitivity of the final
results to this assumption. Where
possible analysis was carried out according
to the "intention to treat"
principles. MAIN RESULTS: 5 studies were
included in the review, with 455
people randomised. No differences were found
regarding positive urine
sample for cocaine metabolites. Scores on
Spielberg State Anxiety
Inventory slightly favoured carbamazepine,
but didn't reach statistical
significance. Dropouts were high in both
groups up to 70% in the placebo
group. Less dropout occurred in the
Carbamazepine group (RR 0.87 95%CI
0.71-1.06). When no retention in treatment
was due to side effects no
differences were found. The number of
participants presenting at least one
side effect, reported in Kranzler (1995),
was higher in the carbamazepine
group (RR 4.33 95% CI 1.45-12.91).
REVIEWER'S CONCLUSIONS: There is no
current evidence supporting the clinical use
of CBZ in the treatment of
cocaine dependence. Larger randomised
investigation must be considered
taking into account that these
time-consuming efforts should be reserved
for medications showing more relevant and
promising evidence. [References:
6]
1278.
Linder N. Handsher R.
German B. Sirota L. Bachman M.
Zinger S.
Mendelson E. Barzilai A.
Title
Controlled trial of immune response of
preterm infants to recombinant
hepatitis B and inactivated poliovirus
vaccines administered
simultaneously shortly after birth.
Source
Archives of Disease in Childhood Fetal &
Neonatal Edition. 83(1):F24-7,
2000 Jul.
Abstract
AIM: The study was conducted to evaluate the
immunogenicity of an early,
extra dose of enhanced inactivated
poliovirus vaccine (IPV) administered
simultaneously with recombinant hepatitis B
vaccine (HBV) to preterm
infants shortly after birth. METHODS: Three
groups were studied. Fifty
preterm infants received IPV intramuscularly
within 24 hours of birth, in
addition to routine recommended childhood
immunisations. Fifty two preterm
infants and 35 full term infants received
routine immunisations only
(routine vaccination timing: HBV at birth, 1
and 6 months of age; IPV at 2
and 4 months; oral polio vaccine (OPV) at 4
and 6 months;
diphtheria-tetanus-pertussis (DTP) at 2, 4,
and 6 months; and Haemophilus
influenzae B vaccine at 2 and 4 months).
Blood samples were taken at
birth, 3 and 7 months of age from all
infants, and at 1 month of age from
preterm infants only. RESULTS: At birth, a
lower percentage of both study
and control preterm infants had
antipoliovirus type 3 titres >/= 1:8 than
full term infants. At 1 and 3 months of age
significantly more early IPV
infants had antipoliovirus type 3 titres
>/= 1:8 than routinely vaccinated
preterm infants (p < 0.05). At 7 months
of age there were no significant
differences in percentage of antipoliovirus
titres >/= 1:8 or geometric
mean times (GMTs) between the early IPV
group and the routinely vaccinated
preterm group. At 3 and 7 months of age, the
percentage of positive
antihepatitis B titres (>/= 1:10) and the
GMT of the early IPV preterm
group did not differ significantly from
those of preterm controls. There
was no significant difference in percentage
of positive antihepatitis B
titres between the early IPV group and full
term controls at any time.
GMTs for hepatitis B antibodies were
significantly lower in the early IPV
preterm group than in full term controls at
3 and 7 months of age.
CONCLUSIONS: Administration of an additional
dose of IPV simultaneously
with routine HBV to preterm infants shortly
after birth provides early
protection from poliovirus and hepatitis B
infection, and does not
interfere with poliovirus antibody
production at the age of 7 months.
1279.
Lindgren S. Nilsson S.
Nassberger L. Verbaan H. Wieslander J.
Title
Anti-neutrophil cytoplasmic antibodies in
patients with chronic liver
diseases: prevalence, antigen specificity and
predictive value for
diagnosis of autoimmune liver disease.
Swedish Internal Medicine Liver
Club (SILK) [see comments].
Source
Journal of Gastroenterology &
Hepatology. 15(4):437-42, 2000 Apr.
Abstract
BACKGROUND: Anti-neutrophil cytoplasmic antibodies
(ANCA) against
proteinase 3 are diagnostic of Wegener's
granulomatosis, but ANCA occur
also in patients with other inflammatory
disorders, such as ulcerative
colitis, primary sclerosing cholangitis
(PSC) and autoimmune hepatitis. As
their predictive value for autoimmune liver
disease remains unknown, we
analysed the prevalence and antigen
specificity of ANCA in patients with
various chronic liver diseases (CLD).
METHODS: We studied sera from 100
patients with primary biliary cirrhosis (PBC),
from 76 with PSC and from
279 with various CLD, consecutively drawn
during a 5-year period at the
time of liver biopsy. The ANCA were detected
by indirect
immunofluorescence (IIF) while the antigen
specificity was characterized
by ELISA by using lactoferrin, neutrophil
elastase, cathepsin G and BPI
(bactericidal/permeability increasing
protein) as antigens. RESULTS: In
PBC, ANCA were detected by IIF in 39
patients (39%). The antigen
reactivity by ELISA was lactoferrin in
seven, elastase in 15, BPI in 20
and cathepsin G in four patients. Four
patients had reactivity against
more than one antigen. In PSC, IIF
demonstrated ANCA in 49 patients (65%).
The antigen reactivity was lactoferrin in
17, elastase in 14, BPI in 20
and cathepsin G in four patients. Twelve
patients showed reactivity
against more than one antigen. In CLD, ANCA
were observed in sera from 55
patients (20%). Nineteen of 45 patients
(42%) with autoimmune liver
disease were ANCA positive versus 36/234
(15%) with non-autoimmune liver
disease (P = 0.0002). Among IIF-positive
patients, antibody reactivity
against lactoferrin was noted in 14,
elastase in 28, BPI in 25 and
cathepsin G in five patients. Twenty-one
patients had reactivity against
more than one antigen. Elastase and BPI
antibodies occurred more
frequently in patients with autoimmune
compared to non-autoimmune liver
disease (P < 0.01). CONCLUSIONS:
Anti-neutrophil cytoplasmic antibodies
are prevalent in patients with chronic liver
diseases, but although they
occur more frequently in patients with
autoimmune liver disease their
specificity and sensitivity for autoimmune
liver disease is low. The
predominant antigens are lactoferrin,
elastase and BPI, but the
correlation between IIF findings and ELISA
reactivity against these
antigens is weak.
1280.
Lodha R. Bagga A.
Title
Traditional Indian systems of medicine.
[Review] [52 refs]
Source
Annals of the Academy of Medicine,
Singapore. 29(1):37-41, 2000 Jan.
Abstract
INTRODUCTION: A number of traditional
systems of medicine exist in India
of which Ayurveda is the most popular.
Despite being in use for more than
3000 years, few properly designed trials
have scientifically examined the
clinical potential of Ayurvedic and other medications.
METHODS: We
reviewed the MEDLINE database to identify
clinical trials conducted using
traditional Indian medicines. Single case
reports were excluded. RESULTS:
Ayurvedic preparations have been
successfully used for the treatment of
bronchial asthma, ischaemic heart disease
and hyperlipidaemia.
Formulations containing curcumin were
reported to reduce inflammation and
disability in double-blind clinical trials
on patients with rheumatoid
arthritis. A number of products are reported
to be useful in patients with
acute viral hepatitis. A multicentric study
by the Indian Council of
Medical Research showed that a preparation
from Pterocarpus marsupium was
effective in reducing levels of blood
glucose and glycosylated haemoglobin
in patients with non-insulin-dependent
diabetes mellitus. In another
multicentric trial, patients with
fistula-in-ano were randomised to
surgery or application of medicated seton
(Ksharsootra). Surgical
treatment led to a faster cure but
recurrence rates were lower with
medicated seton. Administration of extract
from Bacopa monnieri, to
children with mental retardation, was
reported to significantly improve
short-term and long-term memory.
CONCLUSIONS: Evidence-based studies on
the efficacy and safety of traditional
Indian medicines are limited. The
essential ingredient in most formulations is
not precisely defined. High
quality studies are necessary to evaluate
and compare the value of
traditional Indian drugs to modern medicine.
[References: 52]
1281.
MacLennan JM. Shackley F.
Heath PT. Deeks JJ. Flamank C.
Herbert M.
Griffiths H. Hatzmann E. Goilav
C. Moxon ER.
Title
Safety, immunogenicity, and induction of
immunologic memory by a serogroup
C meningococcal conjugate vaccine in
infants: A randomized controlled
trial [see comments].
Source
JAMA.
283(21):2795-801, 2000 Jun 7.
Abstract
CONTEXT: Neisseria meningitidis is a common
cause of meningitis and
septicemia in infants worldwide. Whether a
meningococcal C conjugate
vaccine protects infants against the
serogroup C strain is unknown.
OBJECTIVES: To determine whether a
meningococcal C conjugate vaccine is
safe and immunogenic and induces immunologic
memory in infants. DESIGN:
Single-center, double-blind, randomized
controlled trial in 1995 and 1996.
SETTING: Community, Oxfordshire, England.
PARTICIPANTS: One hundred
eighty-two healthy infants. INTERVENTIONS:
Participants were randomly
assigned to receive vaccination with 0. 5-mL
doses of 1 of 2 lots of
meningococcal C conjugate vaccine (groups 1
and 2; n=60 in each group) or
a hepatitis B control vaccine (group 3;
n=62), administered with routine
immunizations at 2, 3, and 4 months of age.
Approximately half of each
group received meningococcal C conjugate
vaccine and half received plain
meningococcal polysaccharide vaccine (MPS)
at 12 months of age. MAIN
OUTCOME MEASURES: Serum antibodies to
meningococcal C polysaccharide,
assayed by enzyme-linked immunosorbent
assay, and serum bactericidal
activity (SBA), at 2, 3, 4, 5, 12, and 13
months of age; local and
systemic reactions, recorded for 6 days
after each vaccination, compared
by intervention group. RESULTS:
Meningococcal C conjugate vaccine was well
tolerated. After 3 doses, children in groups
1 and 2 achieved
significantly higher meningococcal C IgG
geometric mean concentrations (21
and 17 U/mL, respectively, vs 0.20 U/mL;
P<.001) and SBA titers (629 and
420, respectively, vs 4.1; P<. 001) than
controls. At 12 months, antibody
concentrations had decreased in all groups
but remained significantly
higher in children vaccinated with
meningococcal C conjugate vaccine (SBA,
24 and 16 in groups 1 and 2, respectively,
vs 4.2 in group 3; P<.001).
Following vaccination with MPS at 12 months
of age, SBA in the
meningococcal C conjugate vaccine group was
significantly higher than in
controls (SBA, 789 vs 4.5; P<.001).
CONCLUSIONS: Our data indicate that
meningococcal C conjugate vaccine is safe
and immunogenic and results in
immunologic memory when given with other
routinely administered vaccines
to infants at 2, 3, and 4 months of age.
JAMA. 2000;283:2795-2801
1282.
Mahoney RT. Ramachandran S. Xu Z.
Title
The introduction of new vaccines into
developing countries II. Vaccine
financing. [Review] [38 refs]
Source
Vaccine.
18(24):2625-35, 2000 Jun 1.
Abstract
The development of new vaccines for
important childhood diseases presents
an unparalleled opportunity for disease
control but also a significant
problem for developing countries: how to pay
for them. To help address
this problem, the William H. Gates
Foundation has established a Global
Fund for Children's Vaccine. In this paper,
we discuss the allocation of
this and other similar funds, which we call
Global Funds. We propose that
allocation of the Global Funds to individual
countries be guided in part
by a Vaccine Procurement Baseline (VPB). The
VPB would set a minimum of
0.01% of gross national product (GNP) as an
amount each developing country
would devote to its own vaccine procurement.
When this amount is not
sufficient to procure the vaccines needed by
a developing country, the
Global Funds would meet the shortfall. The
amount required of donors to
maintain the Global Funds would be about
$403 million per year for both
existing EPI vaccines as well as for a
hypothetical group of five new
vaccines costing $0.50 per dose and
requiring three doses per child.
Including program costs, poor developing
countries currently spend about
0.13% of GNP on EPI immunizations. In
contrast, the United States, as one
example donor country, spends about 0.035%
of GNP for childhood
immunization including several new vaccines.
This paper analyzes the
Global Funds requirements for hepatitis B
and Haemophilus influenzae type
b (Hib) vaccines. After a ramp-up period,
needier countries would
eventually require about $62 million for
hepatitis B and $282 million for
Hib at current prices. Various additional
criteria could be used to
qualify countries for participation in the
Global Funds. [References: 38]
1283.
Matsuo I. Ikuno N.
Omagari K. Kinoshita H. Oka M.
Yamaguchi H. Kohno
S.
Mackay IR.
Title
Autoimmune reactivity of sera to hepatocyte
plasma membrane in type 1
autoimmune hepatitis [see comments].
Source
Journal of Gastroenterology. 35(3):226-34, 2000.
Abstract
Type 1 autoimmune hepatitis (AIH-1) is an
organ-specific autoimmune liver
disease for which no tissue-specific
autoantigen has yet been identified.
We examined the reactivity by sensitive
immunoblotting with enhanced
chemiluminescence (IB-ECL) of 43 sera from
patients with AIH-1 and 182
sera from patients with other diseases on
hepatocyte plasma membrane
derived from rat or human liver (RHPM, HHPM)
and separated by aqueous
two-phase partition. The sera studied were
from patients with AIH-1,
primary biliary cirrhosis, chronic viral
hepatitis, and systemic lupus
erythematosus (SLE); and from normal
subjects. Specificity of reactivity
by IB-ECL was sought: (i) by testing sera on
human or rat liver membrane;
(ii) by testing sera on liver or kidney
membrane; (iii) by serial
titration of reactive sera; and (iv) by
testing reactive sera from AIH-1
before and after successful treatment with
prednisolone. The results were
that in AIH-1 there were multiple reactive
components which were not
species-specific, since they were detected
with both RHPM and HHPM, but
were mostly tissue-specific for liver. There
was no significant
correlation between antinuclear antibodies
(ANA) titer and the frequencies
of sera reactivities against RHPM. Most of
these reactive components were
demonstrable at a lesser frequency in other
liver diseases and in SLE.
There was a striking decrease in reactivity
by IB-ECL of AIH-1 sera with
liver membrane after clinical remission,
further suggesting that
differences between AIH-1 and other
inflammatory liver diseases and SLE
are predominantly quantitative rather than
qualitative. However, our study
did point to candidate liver membrane
antigens with molecular sizes of
136, 116, 81, and 49 kDa, additional to
components previously described by
others. The molecular identification of
these prominent reactants with
AIH-1 sera could prove informative for ascertaining
pathogenesis.
1284.
Milkiewicz P. Mutimer D.
Hubscher SG. Elias E.
Title
Autoimmune liver disease in patients with
neoplastic diseases.
Source
European Journal of Gastroenterology &
Hepatology. 11(5):569-73, 1999
May.
Abstract
BACKGROUND: Development of de novo
autoimmune liver disease has not been
well documented in patients with malignant
diseases. METHODS/RESULTS: In
this paper we report on a series of six
patients with neoplastic disorders
who acquired liver disease with autoimmune
features. Five patients had
suffered from haematological neoplasms and
one from colonic cancer. In two
patients, liver disease was detected at the
time of presentation with
malignancy. In the remaining four, all of
whom were successfully treated
for malignancies, features of liver disease
presented at intervals 24-72
months after the cancer diagnosis. Twelve
liver specimens (11 biopsies and
one hepatectomy specimen) were obtained at
time intervals of 1-76 months
after initial presentation of neoplastic
disease. Biopsies from three
patients showed features of hepatitis (one
acute, one sub-acute, one
chronic). Two patients had histological
features suggestive of an overlap
syndrome (one autoimmune hepatitis/primary
biliary cirrhosis, one
autoimmune hepatitis/primary sclerosing
cholangitis). The sixth patient
had features of autoimmune cholangiopathy.
All but one responded well to
steroid therapy with complete clinical and
biochemical remission obtained
4 weeks to 8 months after steroid
introduction. We discuss briefly
possible aetiologies of autoimmune liver
disease in these patients.
CONCLUSIONS: Autoimmune liver disease may be
precipitated by therapy for
neoplastic disease or malignant disease
itself. The unusually
heterogeneous clinicopathological findings
in this group as well as the
response to treatment support the concept of
a wide spectrum of
manifestations of autoimmune liver disease.
The results may also suggest
that autoimmune liver disease may be possibly
added to the list of
paraneoplastic syndromes. Further
prospective studies are required to
confirm a causal association and to
determine whether the mechanisms
involved are disease- or treatment-related.
1285.
Modahl LE. Lai MM.
Title
Hepatitis delta virus: the molecular basis
of laboratory diagnosis.
[Review] [203 refs]
Source
Critical Reviews in Clinical Laboratory
Sciences. 37(1):45-92, 2000 Feb.
Abstract
Infection with hepatitis delta virus (HDV),
a satellite virus of hepatitis
B virus (HBV), is associated with severe and
sometimes fulminant
hepatitis. The traditional methods for the
diagnosis of HDV infection,
such as detection of serum anti-HD
antibodies, are sufficient for the
clinical diagnosis of delta infection.
However, such techniques lack the
sensitivity and specificity required to more
accurately characterize the
nature of HDV infection and to assess the
efficacy of therapies. Recent
improvements in molecular techniques, such
as HDV RNA hybridization and
RT-PCR, have provided increased diagnostic
precision and a more thorough
understanding of the natural course of HDV
infection. These advances have
enhanced the clinician's ability to
accurately evaluate the stage of HDV
infection, response to therapy, and occurrence
of reinfection after
orthotopic liver transplant. This review
focuses on the recent advances in
the understanding of the molecular biology
of HDV and in the laboratory
diagnosis of HDV infection. [References:
203]
1286.
Muratori L. Parola M.
Ripalti A. Robino G. Muratori P.
Bellomo G.
Carini
R. Lenzi M. Landini MP. Albano
E. Bianchi FB.
Title
Liver/kidney microsomal antibody type 1
targets CYP2D6 on hepatocyte
plasma membrane [see comments].
Source
Gut.
46(4):553-61, 2000 Apr.
Abstract
BACKGROUND: Liver/kidney microsomal antibody
type 1 (LKM1) is the marker
of type 2 autoimmune hepatitis (AIH) and is
detected in up to 6% of
patients with hepatitis C virus (HCV)
infection. It recognises linear and
conformational epitopes of cytochrome
P450IID6 (CYP2D6) and may have liver
damaging activity, provided that CYP2D6 is
accessible to effector
mechanisms of autoimmune attack. METHODS:
The presence of LKM1 in the
plasma membrane was investigated by indirect
immunofluorescence and
confocal laser microscopy of isolated rat
hepatocytes probed with 10 LKM1
positive sera (five from patients with AIH
and five from patients with
chronic HCV infection) and a rabbit
polyclonal anti-CYP2D6 serum. RESULTS:
Serum from both types of patient stained the
plasma membrane of
non-permeabilised cells, where the
fluorescent signal could be visualised
as discrete clumps. Conversely,
permeabilised hepatocytes showed diffuse
submembranous/cytoplasmic staining.
Adsorption with recombinant CYP2D6
substantially reduced plasma membrane
staining and LKM1 immunoblot
reactivity. Plasma membrane staining of LKM1
colocalised with that of
anti-CYP2D6. Immunoprecipitation experiments
showed that a single 50 kDa
protein recognised by anti-CYP2D6 can be
isolated from the plasma membrane
of intact hepatocytes. CONCLUSIONS: AIH and
HCV related LKM1 recognise
CYP2D6 exposed on the plasma membrane of
isolated hepatocytes. This
observation supports the notion that
anti-CYP2D6 autoreactivity may be
involved in the pathogenesis of liver
damage.
1287.
No Abstract
1288.
Obermayer-Straub
P. Strassburg CP. Manns MP.
Title
Target proteins in human autoimmunity:
cytochromes P450 and UDP-
glucuronosyltransferases. [Review] [112
refs]
Source
Canadian Journal of Gastroenterology. 14(5):429-39, 2000 May.
Abstract
Cytochromes P450 (CYPs) and
UDP-glucuronosyltransferases (UGTs) are
targets of autoantibodies in several hepatic
and extrahepatic autoimmune
diseases. Autoantibodies directed against
hepatic CYPs and UGTs were first
detected by indirect immunofluorescence as
antiliver and/or kidney
microsomal antibodies. In autoimmune
hepatitis (AIH) type 2, liver and/or
kidney microsomal (LKM) type 1
autoantibodies are detected and are
directed against CYP2D6. About 10% of AIH-2
sera further contain LKM-3
autoantibodies directed against family 1
UGTs. Chronic infections by
hepatitis C virus and hepatitis delta virus
may induce several autoimmune
phenomena, and multiple autoantibodies are
detected. Anti-CYP2D6
autoantibodies are detected in up to 4% of
patients with chronic hepatitis
C, and anti-CYP2A6 autoantibodies are
detected in about 2% of these
patients. In contrast, 14% of patients with
chronic hepatitis delta virus
infections generate anti-UGT autoantibodies.
In a small minority of
patients, certain drugs are known to induce
immune-mediated, idiosyncratic
drug reactions, also known as 'druginduced
hepatitis'. Drug-induced
hepatitis is often associated with autoantibodies
directed against hepatic
CYPs or other hepatic proteins. Typical
examples are tienilic acid-induced
hepatitis with anti-CYP2C9, dihydralazine
hepatitis with anti-CYP1A2,
halothane hepatitis with anti-CYP2E1 and
anticonvulsant hepatitis with
anti-CYP3A. Recent data suggest that
alcoholic liver disease may be
induced by mechanisms similar to those that
are active in drug-induced
hepatitis. Autoantibodies directed against
several CYPs are further
detected in sera from patients with the
autoimmune polyglandular syndrome
type 1. Patients with autoimmune
polyglandular syndrome type 1 with
hepatitis often develop anti-CYP1A2;
patients with adrenal failure develop
anti-CYP21, anti- CYP11A1 or CYP17; and
patients with gonadal failure
develop anti-CYP11A1 or CYP17. In idiopathic
Addison disease, CYP21 is the
major autoantigen. [References: 112]
1289.
Pessayre D. Mansouri A.
Haouzi D. Fromenty B.
Title
Hepatotoxicity due to mitochondrial
dysfunction. [Review] [47 refs]
Source
Cell
Biology & Toxicology. 15(6):367-73,
1999.
Abstract
Mitochondria are involved in fatty acid
beta-oxidation, the tricarboxylic
acid cycle, and oxidative phosphorylation,
which provide most of the cell
energy. Mitochondria are also the main source
of reactive oxygen species
in the cell and are involved in cell demise
through opening of the
mitochondrial permeability transition pore.
It was therefore to be
expected that mitochondrial dysfunction
could be a major mechanism of
drug-induced liver disease. Microvesicular
steatosis (which may cause
liver failure, coma, and death) is the
consequence of severe impairment of
mitochondrial beta-oxidation. Endogenous
compounds (such as cytokines or
female sex hormones) or xenobiotics
(including toxins such as ethanol and
drugs such as aspirin, valproic acid,
ibuprofen, or zidovudine) can
inhibit beta-oxidation directly or through a
primary effect on the
mitochondrial genome or the respiratory
chain itself. In some patients,
infections and cytokines, or inborn errors
of beta-oxidation enzymes or
the mitochondrial genome, may favor the
appearance of drug-induced
microvesicular steatosis. Nonalcoholic
steatohepatitis may develop under
conditions causing prolonged,
microvesicular, and/or macrovacuolar
steatosis. In this condition, chronic
impairment of mitochondrial
beta-oxidation (causing steatosis) and the
respiratory chain (increasing
the production of ROS) lead to lipid
peroxidation, which, in turn, may
cause the diverse lesions of
steatohepatitis, namely, necrosis,
inflammation, Mallory's bodies, and
fibrosis. Finally, mitochondria are
involved in several forms of drug-induced
cytolytic hepatitis, through
inhibition or uncoupling of respiration or
through a drug-induced or
reactive metabolite-induced mitochondrial
permeability transition. The
latter effect commits hepatocytes to either
apoptosis or necrosis,
depending on the number of organelles that
have undergone the permeability
transition. [References: 47]
1290.
Ray RB. Meyer K.
Ray R.
Title
Hepatitis C virus core protein promotes
immortalization of primary human
hepatocytes.
Source
Virology.
271(1):197-204, 2000 May 25.
Abstract
Hepatitis C virus (HCV) core protein has
many intriguing properties as a
viral factor and is implicated in cell
growth regulation. In this study,
the cell growth regulation potential of HCV
core protein was investigated
by introduction of the core genomic region
into primary human hepatocytes,
a natural host for virus replication and
tropism. Core-transfected primary
human hepatocytes displayed altered cell
morphology resembling that of
low-differentiated epithelial cells. Those
cells retained an immortalized
phenotype and exhibited continuous growth
after more than 50 passages over
2 years. Stable hepatocyte transfectants
exhibited albumin secretion and
HCV core protein expression. Telomerase
activity, a characteristic of
immortalized or transformed cells, was
evident in the transfected
hepatocytes immediately after senescence.
Anchorage-independent growth of
the immortalized hepatocytes provided
further evidence for a transformed
phenotype. Results from these studies
suggest that the HCV core protein
promotes primary human hepatocytes to an
immortalized phenotype, which may
predispose cells over an extended period of
time to undergo a transforming
event. Thus, HCV core protein appears to
contribute to virus-mediated
pathogenesis in a persistently infected
host. Copyright 2000 Academic
Press.
1291.
Roberts EA.
Title
Autoimmune hepatitis. [Review] [39 refs]
Source
Indian Journal of Pediatrics. 62(5):525-31, 1995 Sep-Oct.
Abstract
Autoimmune hepatitis can present as either
acute or chronic disease in
children. Clinical and laboratory features,
including association with
extrahepatic autoimmune syndromes and prompt
response to immunosuppressive
treatment, circulating autoantibodies and
hypergammaglobulinemia, suggest
an immune etiology. However, the disease
mechanism remains uncertain.
Different types of autoimmune hepatitis are
defined on the basis of which
autoantibodies are present: anti-smooth
muscle (type 1), anti-liver/kidney
microsomal (type 2), or anti-soluble liver
antigen (type 3). Diseases
which may be clinically similar to
autoimmune hepatitis must be excluded
before the diagnosis of autoimmune hepatitis
is established: Wilson's
disease, primary sclerosing cholangitis,
chronic hepatitis B or C, and
drug-induced liver disease are among the
most important entities.
Corticosteroids alone or with azathioprine
constitute the usual treatment
for autoimmune hepatitis. Although some
children achieve a complete
remission, or even recovery, and can stop
immunosuppressive treatment,
others required low-dose prednisone
treatment indefinitely. [References:
39]
1292.
Safary A. Beck J.
Title
Vaccination against hepatitis B: current
challenges for Asian countries
and future directions. [Review] [40 refs]
Source
Journal of Gastroenterology &
Hepatology. 15(4):396-401, 2000 Apr.
Abstract
AIMS: To review the current status of
hepatitis B immunization programmes
as well as future issues concerning
hepatitis B immunization in Asian
countries. METHODS: Pertinent literature was
identified via in-house and
MEDLINE (1980-99) searches and references
cited in published articles.
Articles within the Proceedings of the IX
Triennial International
Symposium on Viral Hepatitis and Liver
Disease provided valuable
state-of-the-art resource data. RESULTS:
Chronic hepatitis B infection is
responsible for 75-90% of primary
hepatocellular carcinoma, one of the 10
most common cancers worldwide. Hepatitis B
and its chronic sequelae can
potentially be eradicated through vaccines
that have been shown to be
95-99% efficacious in preventing development
of the disease or the carrier
state in immunized infants. Approximately
75% of the world's hepatitis B
carriers live in Asian countries wherein
wide variations in immunization
strategies exist. Vaccination programmes in
hyperendemic Asian countries
have elicited decreases in the incidence of
acute and chronic infections
as well as a decrease in chronic carriers in
the unvaccinated population.
Decreases in the incidence of hepatocellular
carcinoma have been recorded
in Taiwan and Singapore after at least 10
years of universal hepatitis B
immunization programmes. CONCLUSIONS: In
Asian countries currently without
nationwide hepatitis B programmes,
utilization of the existing vaccination
infrastructure for administration of other
World Health Organization
Expanded Programme on Immunization vaccines
will provide the most
economical and efficient means of
administration of the hepatitis B
vaccine. [References: 40]
1293.
Shamsuzzaman SM. Haque R. Hasin SK.
Hashiguchi Y.
Title
Evaluation of indirect fluorescent antibody
test and enzyme-linked
immunosorbent assay for diagnosis of hepatic
amebiasis in Bangladesh.
Source
Journal of Parasitology. 86(3):611-5, 2000 Jun.
Abstract
Serum samples of 31 amebic liver abscess
(ALA) patients, 8 amebic
hepatitis (AH) patients, and 60 controls
were tested for anti-amebic IgG
by enzyme-linked immunosorbent assay (ELISA)
and indirect fluorescent
antibody tests (IFAT). Sera of 29 (93.6%)
ALA and 6 (75%) AH patients and
2 (3.3%) control subjects were positive by
IFAT. Anti-amebic antibody
titer above the cutoff point (= 0.168; x + 2
SD of control sera) was
observed in sera of 27 (87%) ALA, 4 (50%)
AH, and 1 (1.7%) control by
ELISA. All the 8 pus samples were positive
for anti-amebic antibodies by
IFAT and ELISA. Sensitivity of ELISA was 87%
for ALA, with a positive
predictive value of 0.96, and 50% for AH
cases, with a positive predictive
value of 0.80. The sensitivity of IFAT was
93.6% for ALA, with a positive
predictive value of 0.94, and 75% for AH,
with a positive predictive value
of 0.75. When pus samples were tested, the
sensitivity was 100% for both
tests. The specificity was 98.3% for ELISA
and 96.7% for IFAT. Although
not significant, IFAT was found more
sensitive than ELISA (P>0.05).
1294.
Sharara AI.
Title
Diagnosis and management of chronic
hepatitis C. [Review] [32 refs]
Source
Journal Medical Libanais - Lebanese Medical
Journal. 47(6):339-42, 1999
Nov-Dec.
Abstract
Chronic HCV infection is a major cause of
chronic liver disease, cirrhosis
and hepatocellular carcinoma worldwide. The
disease is indolent or
subclinical in the majority of patients but
alcohol consumption and older
age at infection may be associated with an
accelerated course. Current
diagnostic modalities are highly sensitive
and specific in confirming the
diagnosis and may help predict response to
therapy. Treatment with
interferon is effective in clearing the
virus in a small number of
patients but the addition of ribavirin results in an enhanced
overall
chance of viral eradication. The development
of an effective vaccine to
HCV is presently encumbered by the presence
of multiple viral genomic
subtypes and the high rate of spontaneous
viral mutation leading to
limited efficacy of neutralizing antibodies.
[References: 32]
1295.
Strickland
DK. Riely CA. Patrick CC. Jones-Wallace
D. Boyett JM.
Waters B.
Fleckenstein JF. Dean PJ. Davila R.
Caver TE. Hudson MM.
Title
Hepatitis C infection among survivors of
childhood cancer.
Source
Blood.
95(10):3065-70, 2000 May 15.
Abstract
Preliminary reports have suggested that
survivors of childhood cancer and
aplastic anemia who are infected with the
hepatitis C virus (HCV) have a
low risk for progression to significant
liver disease. Among our surviving
patients who were transfused between 1961
and March 1992, 77 (6.6% of
surviving patients tested thus far) have
evidence of HCV infection,
whereas 4 surviving patients who were
transfused after March 1992 are
HCV-infected. One patient chronically
infected with HCV died of liver
failure, and 2 patients died of
hepatocellular carcinoma. To characterize
the risk for these and other complications,
65 patients are enrolled in a
longitudinal study of HCV infection, of whom
58 (89.2%) had circulating
HCV RNA at the time of protocol enrollment,
with genotypes 1A and 1B most
commonly isolated. Most enrolled patients
have few or no symptoms, carry
out normal activities, and have normal liver
function. To date, 35
patients have undergone liver biopsy for
abnormal liver function since the
diagnosis of primary malignancy; central
pathology review shows 28 (80%)
have chronic active hepatitis, 25 (71%) have
fibrosis, and 3 (9%) have
cirrhosis. These preliminary data suggest
that though most survivors of
childhood cancer who are infected with HCV
are clinically well, some are
at risk for clinically significant liver
disease. Identification of other
HCV-infected patients and prospective
monitoring of this cohort are
ongoing to determine the risk for, and to
identify factors associated with
the progression of, liver disease.
1296.
Takeda K. Hayakawa Y.
Van Kaer L. Matsuda H. Yagita H.
Okumura K.
Title
Critical contribution of liver natural
killer T cells to a murine model of
hepatitis.
Source
Proceedings of the National Academy of
Sciences of the United States of
America.
97(10):5498-503, 2000 May 9.
Abstract
Natural killer T (NKT) cells constitute a
distinct subpopulation of T
cells with a unique antigen specificity,
prompt effector functions, and an
unusual tissue distribution. NKT cells are
especially abundant in the
liver, but their physiological function in
this organ remains unclear. In
the present study, we examined the possible
contribution of NKT cells to a
murine model of hepatitis induced by i.v.
injection of Con A.
CD1-deficient mice lacking NKT cells were
highly resistant to Con
A-induced hepatitis. Adoptive transfer of
hepatic NKT cells isolated from
wild-type mice, but not from FasL-deficient
gld mice, sensitized
CD1-deficient mice to Con A-induced
hepatitis. Furthermore, adoptive
transfer of hepatic mononuclear cells from
wild-type mice, but not from
CD1-deficient mice, sensitized gld mice to
Con A-induced hepatitis. Upon
Con A administration, hepatic NKT cells
rapidly up-regulated cell surface
FasL expression and FasL-mediated
cytotoxicity. At the same time, NKT
cells underwent apoptosis leading to their
rapid disappearance in the
liver. These results implicated FasL
expression on liver NKT cells in the
pathogenesis of Con A-induced hepatitis,
suggesting a similar pathogenic
role in human liver diseases such as
autoimmune hepatitis.
1297.
Tarao K. Rino Y.
Takemiya S. Tamai S. Ohkawa S.
Sugimasa Y. Miyakawa
K.
Morinaga S. Yoshida M. Shibuya A.
Kokubu S. Kakita A. Endo O.
Title
Close association between high serum ALT and
more rapid recurrence of
hepatocellular carcinoma in hepatectomized
patients with HCV-associated
liver cirrhosis and hepatocellular
carcinoma.
Source
Intervirology. 43(1):20-6, 2000.
Abstract
We investigated whether or not a high serum
alanine aminotransferase (ALT)
level is associated with a more rapid recurrence
of hepatocellular
carcinoma (HCC) in hepatectomized patients
with hepatitis C virus
(HCV)-associated liver cirrhosis (LC)
(HCV-LC) and HCC. Thirty-three
hepatectomized patients with HCV-LC and HCC
of a single nodule who had no
histologic evidence of portal or hepatic
vein invasion and who had been
followed up for more than 3 years were
included in the study. They were
subdivided into two groups according to
their serum ALT levels, ALT being
a well-known marker of inflammatory necrosis
in the liver. Seventeen
patients whose serum ALT levels showed
several peaks or plateaus above 80
international units (IU) were designated as
the high ALT group, and 16
patients whose serum ALT levels showed a
sustained low level below 80 IU
until the first recurrence were designated
as the low ALT group, and the
interval between hepatectomy and the first
recurrence was observed. In the
high ALT group, HCC recurred within 3 years
in 70.6% of the patients. In
contrast, it recurred in only 18.8% of the
low ALT group within the same
period (p < 0.05). There was a
significant difference (p = 0.0201) between
the two groups in the cumulative
nonrecurrence rate. The mean interval in
recurrent patients between hepatectomy and
the first recurrence in the
high ALT group (23.6 +/- 2.8 months; mean
+/- SE) was significantly (p <
0.02) shorter than that in the low ALT group
(49.3 +/- 9.7 months). The
expected interval between hepatectomy and
recurrence was as short as 2.8
+/- 0.5 years (mean +/- SE) in the high ALT
group, compared with 5.8 +/-
0.7 years in the low ALT group (p <
0.05). These results showed that the
recurrence of HCC was accelerated in the
high ALT group, suggesting that
suppression of the rise in ALT level after
hepatectomy by treatment with
anti-inflammatory drugs may prolong the
interval until recurrence by about
2 years in hepatectomized patients with HCC
and HCV-LC. Copyright 2000 S.
Karger AG, Basel.
1298.
Ulmer SC.
Title
Hepatocellular carcinoma. A concise guide to
its status and management.
[Review] [24 refs]
Source
Postgraduate Medicine. 107(5):117-24, 2000 May 1.
Abstract
Although common worldwide, hepatocellular
carcinoma is relatively rare in
the United States. However, for unknown
reasons, the incidence is rising.
Multiple causes exist, but chronic viral
hepatitis in the setting of
cirrhosis is probably the most common.
Despite limitations, AFP
measurement and multiple-phase abdominal CT
are the most sensitive tests
for diagnosis. Surgical resection and liver
transplantation are at present
the only treatment options that offer
potential for long-term survival or
cure in limited-stage hepatocellular
carcinoma. Otherwise, the prognosis
is poor, and 1-year survival is rare. Future
efforts should focus on
improving detection of early-stage disease
and improving preventive
measures to reduce viral hepatitis
infection, transmission, and
progression. [References: 24]
1299.
Vyas GN.
Title
Immunobiology of persistent blood-borne
viral infections. [Review] [17
refs]
Source
Developments in Biological
Standardization. 102:9-17, 2000.
Abstract
Host-virus interactions have co-evolved to
play an interactive role in the
pathogenesis of viral infections and their
disease outcome. Host responses
to viral infections, including the
cell-mediated and humoral immune
responses, have been a subject of intensive
research in virology and
immunology. Definition of specific cellular
receptors for cellular entry
of the agents, the rates of their
intracellular viral replication, the
rates of turnover of circulating virions,
persistence of viral infection
possibly due to inadequate immune responses,
and continued formation of
circulating immune complexes provide the
framework for our current
understanding of the immunopathology of
virally induced disease. Among the
multiple blood-borne viruses (BBV)
transmissible through transfusion,
hepatitis B virus (HBV), hepatitis C virus
(HCV), and human
immunodeficiency viruses (HIV-1/-2) are
relatively more important than
several other viruses. Not only do they
establish asymptomatic persistent
infections with occasional oncogenic
sequelae, but they also cause
significant morbidity and mortality when
transmitted through transfusion
of blood and blood products. Molecular
characterization of these agents
and their in vitro inactivation and removal
from blood have become key
issues in contemporary transfusion safety
since the advent of AIDS.
Because many of the BBV are associated with
white blood cells that have no
therapeutic benefit in haemotherapy, simple
filtration-removal of
leukocytes from donated blood confers a dual
benefit of immunological and
virological safety in transfusion medicine.
[References: 17]
1300.
Walsh K. Alexander G.
Title
Alcoholic liver disease. [Review] [45 refs]
Source
Postgraduate Medical Journal. 76(895):280-6, 2000 May.
Abstract
Alcohol is a major cause of liver cirrhosis
in the Western world and
accounts for the majority of cases of liver
cirrhosis seen in district
general hospitals in the UK. The three most
widely recognised forms of
alcoholic liver disease are alcoholic fatty
liver (steatosis), acute
alcoholic hepatitis, and alcoholic
cirrhosis. The exact pathogenesis of
alcoholic liver injury is still not clear
but immune mediated and free
radical hepatic injury are thought to be
important. There is increasing
interest in genetic factors predisposing to
hepatic injury in susceptible
individuals. Diagnosis is based on accurate
history, raised serum markers
such as gamma-glutamyltransferase, mean
corpuscular volume, and IgA and
liver histology when obtainable. Abstinence
is the most important aspect
of treatment. Newer drugs such as
acamprosate and naltrexone are used to
reduce alcohol craving. Vitamin supplements
and nutrition are vital while
corticosteroids have a role in acute
alcoholic hepatitis where there is no
evidence of gastrointestinal haemorrhage or
sepsis. Liver transplantation
has excellent results in abstinent patients
with end stage liver disease
but there are concerns about recidivism
after transplant. [References: 45]
1301.
Ward BJ.
Title
Vaccine adverse events in the new
millennium: is there reason for concern?
[see comments]. [Review] [62 refs]
Source
Bulletin of the World Health
Organization. 78(2):205-15, 2000.
Abstract
As more and more infectious agents become
targets for immunization
programmes, the spectrum of adverse events
linked to vaccines has been
widening. Although some of these links are
tenuous, relatively little is
known about the immunopathogenesis of even
the best characterized
vaccine-associated adverse events (VAAEs).
The range of possible use of
active immunization is rapidly expanding to
include vaccines against
infectious diseases that require cellular
responses to provide protection
(e.g. tuberculosis, herpes viral
infections), therapeutic vaccines for
chronic infections (e.g. human
immunodeficiency virus (HIV) infection,
viral hepatitis B and C), and vaccines
against non-infectious conditions
(e.g. cancer, autoimmune diseases). Less
virulent pathogens (e.g.
varicella, rotavirus in the developed world)
are also beginning to be
targeted, and vaccine use is being justified
in terms of societal and
parental "costs" rather than in
straightforward morbidity and mortality
costs. In the developed world the paediatric
immunization schedule is
becoming crowded, with pressure to
administer increasing numbers of
antigens simultaneously in ever simpler
forms (e.g. subcomponent, peptide,
and DNA vaccines). This trend, while
attractive in many ways, brings
hypothetical risks (e.g. genetic
restriction, narrowed shield of
protection, and loss of randomness), which
will need to be evaluated and
monitored. The available epidemiological and
laboratory tools to address
the issues outlined above are somewhat
limited. As immunological and
genetic tools improve in the years ahead, it
is likely that we shall be
able to explain the immunopathogenesis of
many VAAEs and perhaps even
anticipate and avoid some of them. However,
this will only happen if the
human and financial resources needed for
monitoring and studying vaccine
safety stay in step with the accelerating
pace of vaccine development.
Failure to make such a commitment would put
all immunization programmes at
risk. [References: 62]
1302.
Widera G. Austin M.
Rabussay D. Goldbeck C. Barnett SW.
Chen M.
Leung L.
Otten GR. Thudium K. Selby MJ.
Ulmer JB.
Title
Increased DNA vaccine delivery and
immunogenicity by electroporation in
vivo.
Source
Journal of Immunology. 164(9):4635-40, 2000 May 1.
Abstract
DNA vaccines have been demonstrated to be
potent in small animals but are
less effective in primates. One limiting
factor may be inefficient uptake
of DNA by cells in situ. In this study, we
evaluated whether cellular
uptake of DNA was a significant barrier to
efficient transfection in vivo
and subsequent induction of immune
responses. For this purpose, we used
the technique of electroporation to
facilitate DNA delivery in vivo. This
technology was shown to substantially
increase delivery of DNA to cells,
resulting in increased expression and
elevated immune responses. The
potency of a weakly immunogenic hepatitis B
surface Ag DNA vaccine was
increased in mice, as seen by a more rapid
onset and higher magnitude of
anti-hepatitis B Abs. In addition, the
immunogenicity of a potent HIV gag
DNA vaccine was increased in mice, as seen
by higher Ab titers, a
substantial reduction in the dose of DNA
required to induce an Ab
response, and an increase in CD8+ T cell
responses. Finally, Ab responses
were enhanced by electroporation against
both components of a combination
HIV gag and env DNA vaccine in guinea pigs
and rabbits. Therefore,
cellular uptake of DNA is a significant
barrier to transfection in vivo,
and electroporation appears able to overcome
this barrier.
1303.
Wies I. Brunner S.
Henninger J. Herkel J. Kanzler S.
Meyer zum
Buschenfelde KH. Lohse AW.
Title
Identification of target antigen for SLA/LP
autoantibodies in autoimmune
hepatitis [see comments].
Source
Lancet.
355(9214):1510-5, 2000 Apr 29.
Abstract
BACKGROUND: Autoantibodies are a hallmark of
autoimmune hepatitis, but
most are not disease specific.
Autoantibodies to soluble liver antigen
(SLA) and to liver and pancreas antigen (LP)
have been described as
disease specific, occurring in about 30% of
all patients with autoimmune
hepatitis, but no standardised assays are
available. Methods We tested
2000 serum samples from patients with
various liver diseases and controls
for SLA autoantibodies by inhibition ELISA.
Serum samples positive for SLA
antibodies were used for immunoscreening of
cDNA expression libraries.
Identified clones were tested against a
panel of serum samples positive
for SLA and LP autoantibodies and control
serum samples, and the epitope
mapped by deletion mutants and exonuclease
digestion. FINDINGS: SLA and LP
autoantibodies were identical. Of 2000 serum
samples screened, 35 were
positive for SLA autoantibodies. These
positive samples came from patients
with autoimmune hepatitis; three from
patients with an overlap syndrome
(primary biliary cirrhosis and secondary
autoimmune hepatitis). Expression
cloning and absorption experiments
identified a 422 aminoacid protein
present in two splice variants as the sole
target antigen. Aminoacids
371-409 were critical for immune
recognition. INTERPRETATION: The
identified cDNA encodes the primary target
antigen of SLA/LP
autoantibodies. The SLA/LP antigen has a
previously unknown aminoacid
sequence, and presumably codes for an
unindentified enzyme, suggested to
be UGA-suppressor tRNA-associated protein.
SLA/LP autoantibodies are
disease specific and recognise a dominant
epitope, suggesting a specific
antigen-driven immune response.
Identification of the SLA/LP target
antigen will allow establishment of a
reliable, widely available
diagnostic assay. Furthermore, its role in
the pathogenesis of autoimmune
hepatitis can now be studied.
1304.
Ying C. De Clercq E. Neyts J.
Title
Lamivudine, adefovir and tenofovir exhibit
long-lasting anti-hepatitis B
virus activity in cell culture.
Source
Journal of Viral Hepatitis. 7(1):79-83, 2000 Jan.
Abstract
In this work, we investigated the
anti-hepatitis B virus (HBV) activity of
lamivudine, adefovir, tenofovir, penciclovir
and lobucavir after
short-term (i.e. 24 or 48 h) or continuous
(9 days) exposure of the
HBV-containing cell line, HepG2 2.2.15, to
these drugs. Lamivudine
maintained significant anti-HBV activity
when added for only 24 or 48 h to
the cell cultures compared to when the drug
was present for the whole
period (9 days) on the cells, i.e. 50%
effective concentration (EC50)
values for the inhibition of HBV DNA
synthesis were 0.07 +/- 0.02
microgram ml-1 after 24 h of incubation,
0.02 +/- 0.01 microgram ml(-1)
after 48 h of incubation and 0.0016 +/-
0.001 microgram ml(-1) after 9
days of incubation. Similarly, the
nucleoside phosphonate analogues,
adefovir and tenofovir, retained significant
anti-HBV activity when added
for only a short period of time to the
cells. The EC50 values were 12 +/-
1 microgram ml(-1) (24 h) and 1.0 +/- 0.2
microgram ml(-1) (48 h) vs 0.003
+/- 0.001 microgram ml(-1) (9 days) for
adefovir, and 6.5 +/- 1.1
microgram ml(-1) (24 h) and 0.8 +/- 0.1
microgram ml(-1) (48 h) vs 0.03
+/- 0.02 microgram ml(-1) (9 days) for
tenofovir. In contrast, penciclovir
and lobucavir lost most of their anti-viral
activity when present on the
cells for 48 h or less.
1305.
Zucca E. Roggero E.
Maggi-Solca N. Conconi A. Bertoni F.
Reilly I.
Castelli D.
Pedrinis E. Piffaretti JC. Cavalli F.
Title
Prevalence of Helicobacter pylori and
hepatitis C virus infections among
non-Hodgkin's lymphoma patients in Southern
Switzerland.
Source
Haematologica. 85(2):147-53, 2000 Feb.
Abstract
BACKGROUND AND OBJECTIVE: Several recent
studies have reported a high rate
of previous hepatitis C virus (HCV)
infection in patients with
non-Hodgkin's lymphoma (NHL). However, it
appears that there are marked
geographical differences in the prevalence
of HCV among NHL patients.
There is further controversy concerning a
possible pathogenetic link
between HCV and certain histologic lymphoma
subtypes, in particular MALT
lymphomas, and it has recently been
speculated that HCV might be involved
in the multistep process of gastric lymphoma
genesis, in addition to the
well established role of chronic
Helicobacter pylori infection. The aim of
this study was to investigate the prevalence
of HCV and H. pylori
infections in patients with B-cell NHL in
Southern Switzerland. DESIGN AND
METHODS: One hundred and eighty newly diagnosed
HIV-negative B-cell NHL
patients, consecutively seen at a referral
oncology center in Southern
Switzerland between 1990 and 1995 were
prospectively studied. A
microparticle enzyme immunoassay was used to
detect antibodies to HCV.
Serologic determination of HCV genotype was
done by the Murex method. The
quantitative detection of IgG anti-H. pylori
was performed by the Biorad
GAP test. RESULTS: Infection with HCV was
detected in 17/180 patients
(9.4%; 95% C.I., 6%-15%). This prevalence is
significantly higher than
that observed in a large survey of 5424 new
blood donors from the same
area tested in 1992-97 (0.9%; 95% C.I.,
0.7-1.2). Neither histologic
subtypes nor specific extranodal
presentations of NHL were associated with
a higher prevalence of HCV. HCV serotype 2
(corresponding to genotypes
2a-c) was the most common. HCV infection was
significantly associated with
a shorter progression-free survival at both
univariate and multivariate
analysis. Anti-Helicobacter antibodies were
detected in 81/180 patients
(45%; 95% C.I., 38%-53%) and H. pylori
infection was significantly
associated with the development of primary
lymphomas of the stomach.
INTERPRETATION AND CONCLUSIONS: A high
prevalence of HCV infection was
detected in NHL lymphoma patients and was
associated with a shorter time
to lymphoma progression. HCV infection was
not correlated with primary
gastric presentation or with MALT-type
histology. Our findings further
support the key role of H.pylori infection
in the pathogenesis of primary
gastric lymphoma of MALT-type. The possible
role of HCV in the
pathogenesis of NHL should be further
investigated.
1686. Authors
Aizawa Y.
Shibamoto Y. Takagi I. Zeniya M.
Toda G.
Title
Analysis of factors affecting the appearance
of hepatocellular carcinoma
in patients with chronic hepatitis C. A long
term follow-up study after
histologic diagnosis.
Source
Cancer.
89(1):53-9, 2000 Jul 1.
Abstract
BACKGROUND: Hepatocellular carcinoma (HCC)
occurs more frequently in
patients with hepatitis C virus
(HCV)-related chronic liver disease than
those with hepatitis B virus-related
disease. It is important to assess
the factors affecting the development of
HCC. METHODS: A long term
follow-up study involving patients with
chronic HCV was performed
retrospectively. A total of 153 patients
diagnosed between June 1981 and
November 1990 with chronic HCV with or
without cirrhosis by liver biopsy
were enrolled in a long term follow-up study
(average, 99.4 months) and
the cumulative incidence rate of HCC and
factors affecting the appearance
of HCC were examined. RESULTS: The 5-year
cumulative incidence rate was
9%, the 10-year cumulative incidence rate
was 23%, and the 15-year
cumulative incidence rate was 42%. The
annual rate of incidence increased
as the follow-up period progressed. The
authors selected ten variables and
investigated their effect on the incidence
rate of HCC, including age,
gender, habitual heavy drinking, positivity
of antibody against hepatitis
B virus surface antigen, treatment with
interferon (IFN) during the
follow-up period, maximum and minimum serum
alanine aminotransferase
levels during the follow-up period,
histologic staging, grading, and
irregular regeneration of hepatocytes. Of
the 10 variables, age (> 50
years), habitual heavy drinking, and
histologic staging were determined to
be independent risk factors according to
multivariate Cox proportional
hazards regression analysis. IFN therapy by
itself was not found to be an
independent factor affecting the appearance
of HCC. CONCLUSIONS: In
patients with chronic HCV, the annual
incidence rate of HCC appeared to
increase as the follow-up period progressed.
According to the results of
the current study, the factors that
independently affected the development
of HCC were age, habitual heavy drinking,
and histologic staging.
Copyright 2000 American Cancer Society.
1687. Authors
Berenguer M. Prieto M. Rayon JM. Mora J.
Pastor M. Ortiz V. Carrasco
D.
San Juan F. Burgueno MD. Mir J.
Berenguer J.
Title
Natural history of clinically compensated
hepatitis C virus-related graft
cirrhosis after liver transplantation.
Source
Hepatology.
32(4 Pt 1):852-8, 2000 Oct.
Abstract
The natural history of clinically
compensated hepatitis C virus (HCV)
cirrhosis after liver transplantation is
unknown. This information is
relevant to transplant centers to improve
the management of these patients
and decide the optimal timing for
retransplantation. The aims of the study
were (1) to describe the natural history of
patients with HCV-cirrhosis
transplants in a center with annual liver
biopsies, and (2) to determine
predictors for clinical decompensation,
retransplantation, and mortality
rates. A total of 49 patients with HCV-graft
cirrhosis, 39 clinically
compensated at histologic diagnosis of
cirrhosis (post-liver
transplantation cirrhosis) were included and
followed up for 1 year (15
days-3.5 years). All patients tested were
infected with genotype 1b.
Predictive variables included histologic
activity index (HAI) at
post-liver transplantation cirrhosis, liver
function tests, age, sex, and
maintenance immunosuppression. Eighteen of
39 patients developed at least
1 episode of decompensation after a median
of 7.8 months (4 days-2.6
years; 93% ascites). The cumulative
probability of decompensation was 8%,
17%, and 42% at 1, 6, and 12 months,
respectively. Graft and patient
survival rates were 100%, 85%, and 71% and
100%, 92%, and 74% at 1, 6, and
12 months, respectively. Patient survival
rates dropped significantly once
decompensation developed (93%, 61%, and 41%
at 1, 6, and 12 months,
respectively). Variables associated with
decompensation,
retransplantation, and mortality rate
included a high Child-Pugh score
(>A), low levels of albumin at post-liver
transplantation cirrhosis, and a
short interval between liver transplantation
and post-liver
transplantation cirrhosis. The natural
history of clinically compensated
HCV-graft cirrhosis is shortened when
compared with immunocompetent
patients. If retransplantation is
considered, it should be performed
promptly once decompensation develops.
1688. Authors
Blatt LM.
Mutchnick MG. Tong MJ. Klion FM.
Lebovics E. Freilich B.
Bach N.
Smith C. Herrera J. Tobias H.
Conrad A. Schmid P.
McHutchison JG.
Title
Assessment of hepatitis C virus RNA and
genotype from 6807 patients with
chronic hepatitis C in the United States.
Source
Journal of Viral Hepatitis. 7(3):196-202, 2000 May.
Abstract
Hepatitis C virus (HCV) RNA status and HCV
genotype have become important
tools in the diagnosis and monitoring of
therapy in chronic HCV infection.
To establish a database with respect to HCV
genotype and serum HCV RNA
concentrations in chronic hepatitis C
patients in the United States, we
analysed 6807 chronic hepatitis C patients
who had HCV RNA and HCV
genotype tests conducted at a central
laboratory. The HCV RNA
concentration cut-off for the lower 25th
percentile of this population
(low titre) was 0.9 x 106 copies ml-1. The
median HCV RNA concentration
was 3.5 x 106 copies ml-1 and the cut-off
for the upper 25th percentile
(high titre) was 5 x 106 copies ml-1. Male
patients had a median HCV RNA
concentration of 3.9 x 106 copies ml-1,
which was significantly higher
than the median HCV RNA level for females
(2.75 x 106 copies ml-1; P <
0.001). HCV genotype 1 was detected in 73%
of patients; genotype 2 in 14%;
genotype 3 in 8%; mixed genotype in 4%; and
genotypes 4, 5 and 6 with a
frequency of < 1%. Patients from the
Northeast, Southeast and Midwest had
significantly (P < 0.001) more infections
with genotype 1 than patients
from the Western and Southern regions.
African-American patients were more
likely to be infected with genotype 1 when
compared with Caucasian,
Hispanic or Asian Pacific Islanders (P <
0.001). Patients infected with
HCV genotype 1 and mixed HCV genotypes had
significantly higher serum HCV
RNA concentrations when compared with HCV
genotypes 2 and 3 (P < 0.001 for
all comparisons).
1689.
Authors
Caniatti LM. Tugnoli V. Eleopra
R. Tralli G. Bassi R. De Grandis D.
Title
Cryoglobulinemic neuropathy related to
hepatitis C virus infection.
Clinical, laboratory and neurophysiological
study.
Source
Journal of the Peripheral Nervous
System. 1(2):131-8, 1996.
Abstract
Peripheral neuropathy is frequently reported
in mixed cryoglobulinemia. As
a close relationship has been established
between mixed cryoglobulinemia
and hepatitis C virus (HCV), the clinical,
neurophysiological, and
serologic findings of five patients affected
by neuropathy,
cryoglobulinemia and HCV infection were
investigated. HCV infection was
ascertained by the presence in the serum of
anti-HCV antibodies detected
by enzyme-linked immunosorbent assay(ELISA),
and of HCV RNA assessed by
polymerase chain reaction (PCR). Initial
symptoms included paresthesias
and painful dysesthesias in the legs. Later
on, the patients developed a
mainly asymmetric axonal polyneuropathy or a
multifocal neuropathy
associated with signs of systemic
vasculitis. In this case series we
report the short-term prognosis, as well as
the response to interferon
(IFN) alpha and conventional treatment. The
presence of HCV RNA supports
the hypothesis that a persistent HCV
infection might be involved in the
pathogenesis of mixed cryoglobulinemia and
cryoglobulinemia-associated
disorders.
1690.
Authors
Chattopadhyay D. Sen MR. Aryya NC.
Title
Immunohistopathological reactions for
liver-specific membrane lipo-protein
in experimental autoimmune hepatitis.
Source
Indian Journal of Pathology &
Microbiology. 42(3):291-7, 1999 Jul.
Abstract
Antibody to the hepatocyte membrane protein,
was induced in inbred strain
C57BL/6 and C3H mice by immunisation with
100,000 g supernatant of
syngeneic liver homogenate in CFA. Three
weekly intraperitoneal injection
of 200 ul of liver homogenate with CFA for
continuous 4 weeks gave the
best possible result. Histopathological
changes were characterised mainly
by perivascular inflammatory infiltrates and
hepatocyte necrosis which
mimicked human autoimmune hepatitis. In one
of the immunological
parameters, antibody to hepatocyte membrane
protein (LSP) has been
demonstrate by ouchterlony method in the
test serum of those animals, who
had received weekly doses of liver antigen.
Thus in experimental
autoimmune liver disease, semi-purified
syngeneic liver fluid (S-100)
leads to hepatic destruction and to an
inflammatory process with several
features in common with human chronic
aggressive hepatitis. The presence
of antibody against syngeneic liver antigen
(S-100) in the test sera
emphasizes that hepatocyte membrane protein
does have an important role in
liver tissue pathogenesis and disease
process in experimental model. In
this study we tried to prove that hepatocyte
membrane protein may act as a
target antigen in developing experimental
autoimmune hepatitis.
1691.
Authors
Cote PJ.
Toshkov I. Bellezza C. Ascenzi M.
Roneker C. Ann Graham L.
Baldwin BH.
Gaye K. Nakamura I. Korba BE.
Tennant BC. Gerin JL.
Title
Temporal pathogenesis of experimental
neonatal woodchuck hepatitis virus
infection: increased initial viral load and
decreased severity of acute
hepatitis during the development of chronic
viral infection.
Source
Hepatology.
32(4 Pt 1):807-17, 2000 Oct.
Abstract
Acute hepatitis B virus (HBV) infections
either resolve or progress to
chronicity. Identification of early
deviations in host-virus responses
associated with these outcomes can further
differentiate cause-effect
mechanisms that initiate and maintain
chronicity. Neonatal woodchucks were
infected experimentally with the woodchuck
hepatitis virus (WHV) at 3 days
of age. At 8 or 14 weeks of age (i.e. , the
early- or mid-acute stage of
infection), whole blood and large surgical
biopsies of the liver were
obtained from infected animals and
uninfected controls. These were stored
for later correlating histopathologic
responses and viral load with the
subsequently determined outcome of
infection. As of 1 year postinfection,
half of the surgically treated infected
woodchucks had developed
self-limited infections, while the other
half developed chronic
infections. The self-limited outcome was
characterized by decreased viral
load in acute-phase liver and plasma and a
generally robust acute hepatic
inflammatory response. Comparisons at the
same early time points revealed
that the chronic outcome was characterized
by increasing initial viral
load in liver and plasma, and a detectable,
but diminished, acute hepatic
inflammation. These cotemporal comparisons
indicate that there is an early
host-response deviation during the acute
phase of a developing chronic
infection. Continued analysis of the tissues
banked from this study will
facilitate further temporal characterization
of acute-phase mechanisms
that determine resolution versus chronicity
in WHV infection.
Understanding such mechanisms may be useful
in the rational design of
therapy for established chronic HBV
infection.
1692.
Authors
de La Rosa JM. Escobedo M.
Title
Tuberculosis and other infectious diseases
in the adolescent immigrant.
[Review] [23 refs]
Source
Adolescent Medicine. 11(2):453-66, 2000 Jun.
Abstract
Adolescent medicine physicians are
frequently the initial contact for
adolescents newly arriving in the U.S. and
it is important that they
recognize the needs of their patients. The
adolescent immigrant may be
encountered in a school-based health
setting, private practice, community
health center, or other health care
settings. This article begins with a
review of the categories of immigrants
comprising the adolescent
population. It gives an extensive review of
tuberculosis among
Mexican-American adolescents, detailing
history, epidemiology, diagnosis,
social factors, and treatment modalities. It
further delineates the impact
of Mexican tuberculosis control strategies
on the practice of medicine in
the U.S., and outlines preventive,
diagnostic, and therapeutic strategies
that should be followed in the adolescent
immigrant. This article also
reviews viral hepatitis in its multiple
forms and its impact on the
adolescent immigrant. It concludes by
delineating prevention practices
required for the adolescent immigrant and
summarizes the interventions an
initial contact physician should undertake
upon encountering such
adolescents. [References: 23]
1693.
Authors
Egner W.
Title
The use of laboratory tests in the diagnosis
of SLE. [Review] [149 refs]
Source
Journal of Clinical Pathology. 53(6):424-32, 2000 Jun.
Abstract
ANA IIF is an effective screening assay in
patients with clinical features
of SLE and will detect most anti-ssDNA,
anti-dsDNA, ENAs, and other
autoantibodies. False positives are common.
The clinical importance cannot
be extrapolated from the ANA titre or
pattern, although higher titres (>
1/160) are more likely to be important.
HEp-2 cells are the most sensitive
substrate for ANA detection, but this must
be balanced against an
increased incidence of insignificant
positivity. ANA positive samples
should be subjected to more specific assays
for the diagnosis of SLE. A
combination of ENA (Ro/La/Sm/RNP) and dsDNA
assays will detect most
patients with SLE as long as the
characteristics of the assays used are
well understood. ESR and CRP measurements
provide useful additional
information. Sjogren's syndrome and MCTD
will produce overlapping serology
with SLE, and anti-dsDNA titres are
sometimes seen in autoimmune hepatitis
and rheumatoid arthritis. All results should
be reported in the light of
the clinical details, by an experienced
immunologist. A suggested
diagnostic protocol is outlined in fig 1.
The type of assay used crucially
influences the predictive value of the
tests. ELISA technology dominates
routine laboratory practice, but tends to
produce more false positive and
true weak positive results, which may reduce
the PPV of the test. This can
be minimised by using IgG specific
conjugates and careful assay
validation. The NPV for SLE [figure: see
text] is high for most assays but
the PPV varies. Where necessary,
laboratories should use crithidia or Farr
dsDNA assays to confirm dubious ELISA dsDNA
results, and ID/IB to confirm
dubious ENA results. For monitoring, a
precise, quantitative assay is
required. It is unclear whether the
detection of IgM or low affinity
antibodies has a role here. A combination of
anti-dsDNA, C3, C4, CRP, and
ESR assays provides the most useful clinical
information. Anti-ssDNA
assays are likely to be useful, and are
potentially more robust than
anti-dsDNA assays, but require more
validation. Local validation of
individual assays and EQA participation is
essential. Not all assays that
apparently measure the same antibody
specificities have equal clinical
relevance, even within a single technology.
Insufficient international or
national reference preparations are currently
available for many antibody
specificities to enable effective
standardisation. Quality assurance
schemes reveal large differences in units
reported by different assays for
some analytes, even when calibrated against
an IRP or equivalent reference
preparation. Serial results can therefore
only be compared from the same
laboratory at present. Most autoantibodies
increase during active disease,
but few prospective data are currently
available to justify treatment on
the basis of rising titres. Further
randomised prospective studies are
required to examine the importance of
antibody isotype and affinity in the
monitoring of SLE by individual assay
methods. The most important aspect
of the appropriate use of laboratory assays
is to become familiar with the
limitations of the technology currently in
use in your local laboratory,
and to consult with your clinical
immunologist in cases of doubt,
preferably before commencing serological
screening. [References: 149]
1694.
Authors
Griga T.
Tromm A. Muller KM. May B.
Title
Overlap syndrome between autoimmune
hepatitis and primary sclerosing
cholangitis in two cases.
Source
European Journal of Gastroenterology &
Hepatology. 12(5):559-64, 2000
May.
Abstract
The overlap syndrome between autoimmune
hepatitis and primary sclerosing
cholangitis is a rare condition and only few
cases have been published,
partly associated with ulcerative colitis,
but not with Crohn's disease.
We report an autoimmune hepatitis/primary
sclerosing cholangitis overlap
syndrome in a female patient with Crohn's
disease. In addition, a second
case of overlap syndrome is reported in a
man without inflammatory bowel
disease. A 24-year-old woman was referred
with a 10-month history of
diarrhoea and biochemical changes including
elevated serum levels of
alkaline phosphatase, aspartate
aminotransferase, alanine aminotransferase
and immunoglobulin G. Enzyme linked
immunosorbent assay showed that
antinuclear autoantibodies were elevated.
Immunofluorescence for
perinuclear-staining antineutrophil
cytoplasmatic antibodies was positive.
Diagnostic criteria of definite autoimmune
hepatitis according to the
International Autoimmune Hepatitis Group
were fulfilled. Liver biopsy
simultaneously showed criteria of autoimmune
hepatitis and primary
sclerosing cholangitis. Endoscopic
retrograde cholangiography demonstrated
features of primary sclerosing cholangitis.
Colonoscopy and colonoscopic
biopsies indicated an active Crohn's disease
affecting the terminal ileum
and the ascending and transverse colon.
Furthermore, we report the case of
a 28-year-old man with known primary
sclerosing cholangitis for the
previous 6 years, and who developed jaundice
and a marked increase of
aspartate aminotransferase, alanine
aminotransferase and immunoglobulin G,
leading to the diagnosis of definite
autoimmune hepatitis. A review of the
literature revealed only 16 cases of an
autoimmune hepatitis/primary
sclerosing cholangitis syndrome in patients
without inflammatory bowel
disease or in association with ulcerative
colitis. We report two
additional cases, one case showing an
association with Crohn's disease.
1695.
Authors
Hayashi S.
Ohtake H. Koike M.
Title
Laparoscopic diagnosis and clinical course
of chronic schistosomiasis
japonica.
Source
Acta Tropica. 77(1):133-40, 2000 Oct 23.
Abstract
Laparoscopic findings of nine patients with
chronic schistosomiasis
japonica were analyzed and compared to
hepatic ultrasonograms, computed
tomography (CT) scans and histological
findings from the same patients. In
all nine patients laparoscopy revealed
yellowish, small speckles,
approximately 50 microm in diameter, sparse
or clustered over the liver
surface, which were later found to represent
subcapsular calcified ova of
Schistosoma japonicum. While the liver
surface was almost smooth in mild
schistosomiasis, multiple whitish markings
and irregular, relatively wide,
groove-like septums were seen in more
advanced cases. In severe
schistosomiasis block-like formations of
variable size, separated by
groove-like depressions, made the liver
surface appear like a tortoise
shell. In moderate or severe schistosomiasis
ultrasonography revealed
spotted high echoes and CT scans demonstrated
network patterns and lineal
calcified spots. The liver surface of
chronic schistosomiasis japonica
without re-infection appeared stable without
change over time but with a
tendency to improve. Hepatocellular
carcinoma was initially recorded in
two of the nine patients and follow-up
revealed a further two with the
same diagnosis. However, all these four
cases also had chronic hepatitis C
(HCV). Hepatocellular carcinoma was not
detected in patients without viral
hepatitis, indicating that hepatic viral
infection is more important than
schistosomiasis in promoting the development
of hepatocellular carcinoma.
1696.
Authors
Heile JM.
Fong YL. Rosa D. Berger K.
Saletti G. Campagnoli S. Bensi
G.
Capo S. Coates S. Crawford K. Dong C. Wininger M. Baker G.
Cousens L.
Chien D. Ng P. Archangel P. Grandi G. Houghton M.
Abrignani S.
Title
Evaluation of hepatitis C virus glycoprotein
E2 for vaccine design: an
endoplasmic reticulum-retained recombinant
protein is superior to secreted
recombinant protein and DNA-based vaccine
candidates.
Source
Journal of Virology. 74(15):6885-92, 2000 Aug.
Abstract
Hepatitis C virus (HCV) is the leading
causative agent of blood-borne
chronic hepatitis and is the target of intensive
vaccine research. The
virus genome encodes a number of structural
and nonstructural antigens
which could be used in a subunit vaccine.
The HCV envelope glycoprotein E2
has recently been shown to bind CD81 on
human cells and therefore is a
prime candidate for inclusion in any such
vaccine. The experiments
presented here assessed the optimal form of
HCV E2 antigen from the
perspective of antibody generation. The
quality of recombinant E2 protein
was evaluated by both the capacity to bind its
putative receptor CD81 on
human cells and the ability to elicit
antibodies that inhibited this
binding (NOB antibodies). We show that
truncated E2 proteins expressed in
mammalian cells bind with high efficiency to
human cells and elicit NOB
antibodies in guinea pigs only when purified
from the core-glycosylated
intracellular fraction, whereas the
complex-glycosylated secreted fraction
does not bind and elicits no NOB antibodies.
We also show that
carbohydrate moieties are not necessary for E2
binding to human cells and
that only the monomeric nonaggregated
fraction can bind to CD81. Moreover,
comparing recombinant intracellular E2
protein to several E2-encoding DNA
vaccines in mice, we found that protein
immunization is superior to DNA in
both the quantity and quality of the
antibody response elicited. Together,
our data suggest that to elicit antibodies
aimed at blocking HCV binding
to CD81 on human cells, the antigen of
choice is a mammalian
cell-expressed, monomeric E2 protein
purified from the intracellular
fraction.
1697.
Authors
Hilleman MR.
Title
Vaccines in historic evolution and
perspective: a narrative of vaccine
discoveries.
Source
Journal of Human Virology. 3(2):63-76, 2000 Mar-Apr.
Abstract
The sciences of vaccinology and immunology
were created only two centuries
ago by Jenner's scientific studies of
prevention of smallpox through
inoculation with cowpox virus. This
rudimentary beginning was expanded
greatly by the giants of late 19th- and
early 20th-century biomedical
sciences. The period from 1930 to 1950 was a
transitional era, with the
introduction of chick embryos and minced
tissues for propagating viruses
and rickettsiae in vitro for vaccines.
Modern vaccinology began about 1950
as a continuum following notable advances
made during the 1940s and World
War II. Its pursuit has been based largely
on breakthroughs in cell
culture, bacterial polysaccharide chemistry,
molecular biology, and
immunology which have yielded many live and
killed viral and bacterial
vaccines plus the recombinant-expressed
hepatitis B vaccine. The present
paper was presented as a lecture given at a
Meeting of the Institute of
Human Virology entitled A Symposium on
HIV-AIDS and Cancer Biology,
Baltimore, Maryland, on August 30, 2023 and
recounts, by invitation, more
than 55 years of vaccine research from the
venue of personal experience
and attainment by the author. The paper is
intentionally brief and
truncated with focus only on highlights and
limited referencing. Detailed
recounting and referencing are given
elsewhere in text references 1 and 2.
This narration will have achieved its
purpose if it provides a background
of understanding and guidelines that will
assist others who seek to engage
in creation of new vaccines.
1698.
Authors
Hwang SJ.
Luo JC. Lai CR. Chu CW.
Tsay SH. Lu CL. Wu JC.
Chang FY.
Lee SD.
Title
Clinical, virologic and pathologic
significance of elevated serum
gamma-glutamyl transpeptidase in patients
with chronic hepatitis C.
Source
Chung Hua i Hsueh Tsa Chih - Chinese Medical
Journal. 63(7):527-35, 2000
Jul.
Abstract
BACKGROUND: Elevated serum gamma-glutamyl
transpeptidase (GGT) is often
seen in patients with chronic hepatitis C
virus (HCV) infection and is
associated with a poor response to
interferon treatment. The pathogenesis
of these phenomena is unclear. Therefore, we
assessed the prevalence of
elevated serum GGT in Chinese patients with
chronic hepatitis C and
evaluated the clinical, biochemical,
virologic and histologic features of
this phenomenon. METHODS: One hundred and
twelve patients with
biopsy-proven chronic hepatitis C were
enrolled. Patients who were
habitual alcohol drinkers, alcoholics or had
diabetes mellitus were
excluded. RESULTS: Forty-three (38.4%) of
112 patients had elevated serum
GGT (> 60 U/l). Patients with elevated
serum GGT had significantly higher
serum levels of alanine and aspartate
aminotransferases, alkaline
phosphatase and total bilirubin, significantly
higher histologic scores of
liver lobular necro-inflammation and
fibrosis when compared to patients
with normal serum GGT. Elevated serum GGT
was not correlated to serum HCV
RNA titer or HCV genotype. Multivariate
logistic regression analysis
showed that a histologic fibrotic score >
or = 2 was the only
significantly independent predictor
associated with elevated serum GGT.
Fifty-seven of 112 patients completed a
six-month course of interferon
treatment. Patients with elevated serum GGT
had a significantly lower
sustained response rate to interferon when
compared to patients with
normal serum GGT (8% vs 30%, p = 0.042).
CONCLUSIONS: Elevated serum GGT
in chronic hepatitis C patients was
frequently associated with more severe
hepatic fibrosis or cirrhosis and may, in
part, account for poor response
to interferon therapy.
1699.
Authors
Imperiale TF. Said AT. Cummings
OW. Born LJ.
Title
Need for validation of clinical decision
aids: use of the AST/ALT ratio in
predicting cirrhosis in chronic hepatitis C.
Source
American Journal of Gastroenterology. 95(9):2328-32, 2000 Sep.
Abstract
OBJECTIVE: A value of > or = 1 for the
ratio of aspartate
amino-transferase to alanine
aminotransferase (the AST/ALT ratio or AAR)
has been shown to have a positive predictive
value of 100% for the
diagnosis of cirrhosis in patients with
chronic hepatitis C. If validated
on separate cohorts, an AAR > or = 1
might obviate the need for liver
biopsy in some patients with hepatitis C.
METHODS: We attempted to
validate the AAR by abstracting demographic
and clinical data from a
database of consecutive patients with
hepatitis C who had a liver biopsy
between 1993 and 1998. We used definitions,
methods of data collection,
and analyses comparable to those of the
published study. A
hepatopathologist blindly reviewed 49 liver
biopsies for histological
grade and stage. RESULTS: The current cohort
of 177 patients and the
previous cohort of 139 patients were
comparable in mean age (42.3 vs 43.8
yr), percentage of men (63 vs 67),
percentage with an AAR > or =1 (20 vs
17), and Child-Pugh distribution, but
differed in substantial use of
ethanol (11% vs 3.6%; p = 0.01) and in the
prevalence of cirrhosis (23% vs
34%, p = 0.06). Respective sensitivities of
the AAR were 56% and 53%. An
AAR > or =1 had a positive predictive
value of 64% (95% confidence
interval 48-78%) for the current cohort.
Thirteen of 36 patients (36%)
with an AAR > or =1 were incorrectly
identified as having cirrhosis. Of
these 13 patients, 6 had a normal AST and
ALT, 5 had a minimally elevated
AST or ALT, and 1 had advanced fibrosis
without cirrhosis. CONCLUSIONS:
These results suggest that an AAR > or =1
may not be as useful for
predicting cirrhosis in chronic hepatitis C
as previously thought, and
emphasizes the need for validation of
clinical decision aids on
independent patient cohorts.
1700.
Authors
Jacobs RJ.
Margolis HS. Coleman PJ.
Title
The cost-effectiveness of adolescent hepatitis
A vaccination in states
with the highest disease rates.
Source
Archives of Pediatrics & Adolescent
Medicine. 154(8):763-70, 2000 Aug.
Abstract
BACKGROUND: The Advisory Committee on
Immunization Practices has
recommended routine childhood hepatitis A
vaccination in states and
communities where the incidence of disease
exceeds the national average,
but most adolescents are currently
unprotected from infection. OBJECTIVE:
To estimate clinical and economic
consequences of vaccinating adolescents
against hepatitis A in the 10 states with
the highest disease rates.
DESIGN: Decision analysis was used to assess
cost-effectiveness from
societal and health system perspectives.
Parameter estimates were obtained
from national surveillance data, a study of
hepatitis A cases, and an
expert panel. MAIN OUTCOME MEASURES:
Reduction in disease incidence; costs
of vaccination, treatment, and work loss;
years of life saved (YOLS); and
costs per YOLS. RESULTS: In states with the
highest disease rates,
vaccination of adolescents against hepatitis
A would reduce the lifetime
risk of symptomatic infection from 3.3% to
0.7% and prevent loss of 2117
years of life. Vaccination of a single birth
cohort would cost $30.9
million, yet treatment and work loss costs
would decline $14.2 million and
$23.8 million, respectively. Hepatitis A
vaccination would cost the health
system $7902 per YOLS or $13,722 per
discounted YOLS. Results are most
sensitive to variation in the discount rate
and assumptions regarding
long-term vaccine protective efficacy.
CONCLUSIONS: Hepatitis A
vaccination of adolescents in states with
high disease rates would reduce
costs to society. Although health system
costs would increase,
cost-effectiveness is comparable to other
recommended vaccines and
superior to many commonly used medical
interventions. Arch Pediatr Adolesc
Med. 2000;154:763-770
1701.
Authors
Jeffers L.
Title
Hepatocellular carcinoma: an emerging
problem with hepatitis C.
Source
Journal of the National Medical
Association. 92(8):369-71, 2000 Aug.
Abstract
Hepatocellular carcinoma (HCC) is emerging
as a major problem in the
United States, primarily due to the
development of liver cancer in
patients with cirrhosis secondary to the hepatitis
C virus. The diagnosis
of HCC in patients with underlying cirrhosis
can be achieved at an early
stage if appropriate diagnostic measures are
pursued by primary care
physicians and gastroenterologists. African
Americans are particularly
vulnerable in developing HCC since their
response to current therapy for
chronic hepatitis C is less than optimal.
1702.
Authors
Kaakkola S.
Title
Clinical pharmacology, therapeutic use and
potential of COMT inhibitors in
Parkinson's disease. [Review] [109 refs]
Source
Drugs.
59(6):1233-50, 2000 Jun.
Abstract
When peripheral decarboxylation is blocked
by carbidopa or benserazide,
the main metabolic pathway of levodopa is
O-methylation by
catechol-O-methyltransferase (COMT).
Entacapone and tolcapone are new
potent, selective and reversible
nitrocatechol-type COMT inhibitors.
Animal studies have demonstrated that
entacapone mainly has a peripheral
effect whereas tolcapone also inhibits
O-methylation in the brain. In
human volunteers, both entacapone and
tolcapone dose-dependently inhibit
the COMT activity in erythrocytes, improve
the bioavailability and
decrease the elimination of levodopa, and
inhibit the formation of
3-O-methyldopa (3-OMD). Entacapone is
administered with every scheduled
dose of levodopa whereas tolcapone is
administered 3 times daily. The
different administration regimens for these
agents are based on their
different pharmacokinetic and
pharmacodynamic profiles. Both entacapone
and tolcapone enhance and extend the
therapeutic effect of levodopa in
patients with advanced and fluctuating
Parkinson's disease. They prolong
the duration of levodopa effect. Clinical
studies show that they increase
the daily ON time by an average 1 to 3
hours, improve the activities of
daily living and allow daily levodopa dosage
to be decreased.
Correspondingly, they significantly reduce
the daily OFF time. No
comparative studies between entacapone and
tolcapone have been performed.
Tolcapone also appears to have a beneficial
effect in patients with
nonfluctuating Parkinson's disease. The main
adverse effects of the COMT
inhibitors are related to their dopaminergic
and gastrointestinal effects.
Enhancement of dopaminergic activity may
cause an initial worsening of
levodopa-induced adverse effects, such as
dyskinesia, nausea, vomiting,
orthostatic hypotension, sleep disorders and
hallucinations. Levodopa dose
adjustment is recommended to avoid these
events. Tolcapone is associated
with diarrhoea in about 16 to 18% of
patients and entacapone in less than
10% of patients. Diarrhoea has led to
discontinuation in 5 to 6% of
patients treated with tolcapone and in 2.5%
of those treated with
entacapone. Urine discoloration to dark
yellow or orange is related to the
colour of COMT inhibitors and their
metabolites. Elevated liver
transaminase levels are reported in 1 to 3%
of patients treated with
tolcapone but very rarely, if at all, in
patients treated with entacapone.
The descriptions of acute, fatal fulminant
hepatitis and potentially fatal
neurological reactions, such as neuroleptic
malignant syndrome and
rhabdomyolysis, in association with
tolcapone led to the suspension of its
marketing authorisation in the European
Community and Canada. In many
other countries, the use of tolcapone is
restricted to patients who are
not responding satisfactorily to other
therapies. Regular monitoring of
liver enzymes is required if tolcapone is
used. No such adverse reactions
have so far been described for entacapone
and no laboratory monitoring has
been proposed. COMT inhibitors added to
levodopa therapy are beneficial,
particularly in patients with fluctuating
disease. They may be combined
with other antiparkinsonian drugs, such as
dopamine agonists, selegiline
and anticholinergics without adverse
interactions. They provide a new
treatment possibility in patients with
Parkinson's disease who have
problems with their present levodopa
therapy. [References: 109]
1703.
Authors
Kallinowski B. Knoll A. Lindner E. Sanger R.
Stremmel W. Vollmar J.
Zieger B.
Jilg W.
Title
Can monovalent hepatitis A and B vaccines be
replaced by a combined
hepatitis A/B vaccine during the primary
immunization course?.
Source
Vaccine.
19(1):16-22, 2000 Aug 15.
Abstract
A combined hepatitis A/B vaccine (Twinrix
Adult) has been licensed in
Germany since 1997. We investigated possible
differences in immunogenicity
and safety when changing over from
vaccinations with monovalent vaccines
made by different manufacturers to
vaccinations with the combined
hepatitis A/B vaccine in an open,
randomized, multicenter trial. We
therefore compared four different schemes
changing over from concomitant
vaccinations with monovalent vaccines
against hepatitis A and B (Havrix
1440+Engerix-B or Vaqta+Gen H-B-Vax) to
combined vaccination against
hepatitis A+B with three injections of the
combined hepatitis A/B vaccine
(0, 1, and 6 month schedule). Local and
general symptoms were mostly mild
in all five groups. With complete three-dose
course using the combined
vaccine or an early changeover from
monovalent vaccines to the combined
vaccine, higher overall anti-HBs
seroprotection rates and geometric mean
concentrations (GMCs) against hepatitis B
could be achieved as early as
after 2 months as compared to those groups
switching later to the combined
vaccine. This study demonstrated for the
first time that switching from
monovalent hepatitis A and B vaccinations to
the combined hepatitis A and
B vaccination has no negative influence on
the tolerability and improves
the immunogenicity.
1704.
Authors
Konomi N.
Yamaguchi M. Naito H. Aiba N.
Saito T. Arakawa Y. Abe K.
Title
Simultaneous detection of hepatitis B, C,
and G viral genomes by multiplex
PCR method.
Source
Japanese Journal of Infectious
Diseases. 53(2):70-2, 2000 Apr.
Abstract
We established a multiplex polymerase chain
reaction (PCR) method for
simultaneous detection of hepatitis B, C,
and G viral genomes. The levels
of concordance with the data obtained by
conventional single PCR method
were 100% for single infection, 98 to 100%
for double infections, and 92%
for triple infections. This method is not
only suited to rapid,
large-scale epidemiological screening and
clinical diagnosis of those
virus infections occurring alone or in
combination, but is also time- and
cost-effective.
1705.
Authors
Kumar KS.
Malet PF.
Title
Nonalcoholic steatohepatitis. [Review] [38
refs]
Source
Mayo Clinic Proceedings. 75(7):733-9, 2000 Jul.
Abstract
Nonalcoholic steatohepatitis (NASH) is a
liver disease that, until
recently, has been underrecognized as a
common cause of elevated liver
enzymes. This distinct clinical entity is
characterized by liver biopsy
findings similar to those seen in alcoholic
hepatitis but in the absence
of alcohol consumption sufficient to cause
such changes. Patients with
NASH are often middle-aged and obese, with
coexisting diabetes or
hyperlipidemia, but NASH also occurs in
younger lean, otherwise healthy
individuals and even in children. Although
NASH is generally a benign
disorder, it may be progressive, leading to
cirrhosis and complications of
portal hypertension. Liver biopsy remains
the gold standard for diagnosis.
Therapy for NASH remains poorly defined,
although weight reduction and
ursodeoxycholic acid may have a beneficial
effect. [References: 38]
1706.
Authors
Leung W.
Hudson MM. Strickland DK. Phipps S.
Srivastava DK. Ribeiro
RC.
Rubnitz JE. Sandlund JT. Kun LE.
Bowman LC. Razzouk BI. Mathew
P.
Shearer P. Evans WE. Pui CH.
Title
Late effects of treatment in survivors of
childhood acute myeloid leukemia.
Source
Journal of Clinical Oncology. 18(18):3273-9, 2000 Sep 15.
Abstract
PURPOSE: To investigate the incidence of and
risk factors for late
sequelae of treatment in patients who
survived for more than 10 years
after the diagnosis of childhood acute
myeloid leukemia (AML). PATIENTS
AND METHODS: Of 77 survivors (median
follow-up duration, 16. 7 years), 44
(group A) had received chemotherapy, 18
(group B) had received
chemotherapy and cranial irradiation, and 15
(group C) had received
chemotherapy, total-body irradiation, and
allogeneic bone marrow
transplantation. Late complications, tobacco
use, and health insurance
status were assessed. RESULTS: Growth
abnormalities were found in 51% of
survivors, neurocognitive abnormalities in
30%, transfusion-acquired
hepatitis in 28%, endocrine abnormalities in
16%, cataracts in 12%, and
cardiac abnormalities in 8%. Younger age at
the time of diagnosis or
initiation of radiation therapy, higher dose
of radiation, and treatment
in groups B and C were risk factors for the
development of academic
difficulties and greater decrease in height
Z: score. In addition,
treatment in group C was a risk factor for a
greater decrease in weight Z:
score and the development of growth-hormone
deficiency, hypothyroidism,
hypogonadism, infertility, and cataracts.
The estimated cumulative risk of
a second malignancy at 20 years after
diagnosis was 1.8% (95% confidence
interval, 0.3% to 11.8%). Twenty-two
patients (29%) were smokers, and 11
(14%) had no medical insurance at the time
of last follow-up. CONCLUSION:
Late sequelae are common in long-term
survivors of childhood AML. Our
findings should be useful in defining areas
for surveillance of and
intervention for late sequelae and in
assessing the risk of individual
late effects on the basis of age and history
of treatment.
1707.
Authors
Louie M.
Louie L. Simor AE.
Title
The role of DNA amplification technology in
the diagnosis of infectious
diseases. [Review] [81 refs]
Source
CMAJ.
163(3):301-9, 2000 Aug 8.
Abstract
Nucleic acid amplification and detection
methods developed in the past
decade are useful for the diagnosis and
management of a variety of
infectious diseases. The most widely used of
these methods is the
polymerase chain reaction (PCR). PCR assays
can detect rapidly and
accurately the presence of fastidious and
slow-growing microorganisms,
such as Chlamydia, mycoplasmas,
mycobacteria, herpesviruses and
enteroviruses, directly from clinical
specimens. Commercial PCR assays for
the diagnosis of tuberculosis and genital C.
trachomatis infection are now
routinely used in many diagnostic
laboratories. Assays have also been
developed that can detect antimicrobial
resistance and are used to
identify the cause of infection by organisms
that cannot be cultivated.
The value of viral load measurement by
nucleic acid amplification in the
management of patients with HIV infection or
hepatitis C has also been
well established. However, evaluations of
this technology for rapid
microbial diagnosis have generally been
limited by small samples, and the
cost of these assays may be as high as
Can$125 per test. As nucleic acid
amplification methods continue to evolve,
their role in the diagnosis and
management of patients with infectious
diseases and their impact on
clinical outcomes will become better
defined. [References: 81]
1708.
Authors
Manoussakis MN. Moutsopoulos HM.
Title
Sjogren's syndrome: autoimmune epithelitis.
Source
Best Practice & Research in Clinical
Rheumatology. 14(1):73-95, 2000 Mar.
Abstract
Sjogren's syndrome (SS) is a chronic
autoimmune disorder of the exocrine
glands of unknown aetiology, which is
typically associated with focal
lymphocytic infiltrates of glandular tissues
and autoantibody responses
against the Ro(SSA) and La(SSB)
ribonucleoproteins. In almost one-third of
patients disease involves various
extraglandular sites, whereas
approximately 5% of patients may also
develop malignant B-cell lymphoma.
In addition, features of SS are frequently
encountered (5-20%) in patients
with several other autoimmune rheumatic
diseases, and in several respects
these 'secondary' forms may be distinct from
SS found alone (primary-SS),
as well as from each other. The correct
diagnosis and management of SS may
require consideration from various specialists.
Differential diagnosis
includes adverse effects of drugs,
sarcoidosis, lipoproteinaemias,
age-related atrophy, chronic
graft-versus-host disease, lymphomas,
amyloidosis and infection by human
immunodeficiency virus or hepatitis C
virus. Based on the sequential application
of the validated European
classification criteria for SS, a practical
algorithm for diagnosis is
presented. Despite progress in the
understanding of the broad
clinicopathological spectrum of the entity,
its treatment remains largely
empirical and symptomatic. To date, the
decision for systemic therapeutic
intervention is primarily based on the
severity of extraglandular
manifestations.
1709.
Authors
Matheson AJ. Goa KL.
Title
Diphtheria-tetanus-acellular pertussis
vaccine adsorbed (Triacelluvax;
DTaP3-CB): a review of its use in the
prevention of Bordetella pertussis
infection. [Review] [50 refs]
Source
Paediatric Drugs. 2(2):139-59, 2000 Mar-Apr.
Abstract
DTaP3-CB (Triacelluvax) is an acellular
pertussis (aP) vaccine containing
3 antigens from purified Bordetella
pertussis bacteria combined with
diphtheria and tetanus toxoids (DT). In
addition to purified filamentous
haemagglutinin and pertactin, DTaP3-CB
contains pertussis toxin which has
been genetically rather than chemically
detoxified. As shown in
randomised, double-blind clinical trials in
infants, DTaP3-CB elicits an
immune response similar to or greater than
that of whole cell (DTwP)
vaccines. Results of a large multicentre
study comparing DTaP3-CB with 12
acellular and 1 DTwP vaccine indicate that
DTaP3-CB, like all acellular
vaccines, induces variable immune responses
to different pertussis
antigens; however, antibody titres to
pertussis toxin are normally higher
after immunisation with the genetically
detoxified vaccine than with other
3- or 4-component vaccines. When given as a
fourth or fifth booster dose,
DTaP3-CB produced a significant immune
response in infants primed with 3
doses of either a DTaP or DTwP vaccine.
Virtually all infants immunised
with DTaP3-CB had a serological response to
diphtheria and tetanus
toxoids. Data from 2 very large efficacy
studies indicate that DTaP3-CB
has high and long lasting protective
efficacy against culture-confirmed
pertussis which is greater than that of a
2-component vaccine (DTaP2-SB)
and the whole cell DTwP-CON vaccine after a
3-, 5- and 12-month
immunisation schedule and after a 2-, 4- and
6-month schedule with the
DTwP-CON vaccine. However, the DTwP-CON whole
cell vaccine has been noted
for its low immunogenicity in 1 study and
low efficacy and immunogenicity
in another study. On the other hand,
DTaP3-CB vaccine has similar efficacy
to DTaP3-SB (after immunisation at 2, 4 and
6 months), DTaP5-CON and
DTwP-EVANS against culture-confirmed pertussis with > or =21
days cough in
infants immunised according to a 3-, 5- and
12-month schedule. Infants
immunised with DTaP3-CB experienced
significantly fewer adverse events
such as pain, redness, swelling and
irritability than infants given DTwP.
DTaP3-CB has a similar tolerability profile
to other acellular vaccines
and is associated with similar rates of
local tenderness, irritability,
fever (> or =40 degrees C) and persistent
crying. Comparative trials have
shown that infants immunised with DTaP3-CB
had a lower incidence of pain
at the site of injection and fever (> or
=38 degrees C) compared with
other acellular vaccines, although this may
have little clinical
significance. Concomitant administration of
DTaP3-CB with hepatitis B,
oral polio or Haemophilus influenzae type B
vaccines did not affect the
immunogenicity of these other paediatric
vaccines. CONCLUSION: Data from
clinical trials with DTaP3-CB vaccine
indicate that this vaccine induces
high and long lasting efficacy. It is at
least as efficacious as most
whole cell vaccines and generally similar in
efficacy to the most
efficacious acellular pertussis vaccines
containing 3 or more pertussis
antigens. DTaP3-CB is better tolerated than
whole cell vaccines and has a
similar tolerability profile to other
acellular vaccines; the possible
lower risk of severe adverse events remains
to be confirmed. The low
reactogenicity of DTaP3-CB is likely to make
it well tolerated and
therefore well accepted for the immunisation
of infants, thereby enabling
wider implementation of vaccination
programmes. [References: 50]
1710. Authors
Matsumura H. Moriyama M. Goto I. Tanaka N.
Okubo H. Arakawa Y.
Title
Natural course of progression of liver
fibrosis in Japanese patients with
chronic liver disease type C--a study of 527
patients at one
establishment.
Source
Journal of Viral Hepatitis. 7(4):268-75, 2000 Jul.
Abstract
Patients with chronic hepatitis C infection
show a gradual progression of
fibrosis to liver cirrhosis and
hepatocellular carcinoma (HCC). We studied
whether the progression of liver fibrosis
differed among Japanese subjects
who were infected with different hepatitis C
virus (HCV) genotypes. In 527
patients we examined whether there was a relationship between
gender, age,
history of blood transfusion, interval
between date of blood transfusion
and date of liver biopsy or date of
diagnosis of HCC, serum alanine
aminotransferase level, platelet count or
HCV genotype, with the extent of
liver fibrosis, classified into four stages
(F1-F4). Moreover, we compared
the mean rate of liver fibrosis progression
per year in patients with each
HCV genotype. Patients who had a higher
fibrosis score tended to be older,
have a lower platelet count and a longer
interval since blood transfusion
than those who had a lower fibrosis score.
The mean rate of liver fibrosis
progression was 0.12 +/- 0.15 stages per
year after the blood transfusion.
However, the progression rate of liver
fibrosis in patients who had
received a blood transfusion when they were
> or = 30 years of age was
0.19 +/- 0.22, while the progression rate of
liver fibrosis in the
patients who had received a blood
transfusion when they were < 30 years
was 0.09 +/- 0.09. In conclusion, chronic
hepatitis C is a progressive
disease, and patients with genotype 1b, 2a
and 2b have a similar rate of
progression of liver fibrosis. Particular
attention should be paid to
patients who are infected with HCV when >
or = 30 years of age, because
intrahepatic fibrosis rapidly progresses in
these patients.
1711. Authors
Matsuoka S.
Uchiyama K. Kuniyasu Y. Niio Y.
Shima H. Doai K. Oishi
S.
Nojiri Y. Ogata H.
Title
Abnormal pulmonary accumulation of
indium-111 chloride in pneumocystis
carinii pneumonia as detected by bone marrow
scintigraphy.
Source
Clinical Nuclear Medicine. 25(5):361-3, 2000 May.
Abstract
PURPOSE: Unusual pulmonary uptake of In-111
chloride in a patient with
Pneumocystis carinii pneumonia and
autoimmune hepatitis is described.
METHOD: In-111 chloride bone marrow
scintigraphy was performed to evaluate
the bone marrow activity associated with
pancytopenia in a 56-year-old
woman with autoimmune hepatitis. RESULTS: An
In-111 chloride bone marrow
scan showed increased pulmonary uptake
predominantly in both upper lung
fields. P. carinii pneumonia was seen to be
developing as an
immunocompromised complication after
treatment for autoimmune hepatitis.
CONCLUSION: When In-111 chloride bone marrow
scintigraphy shows increased
uptake in the lungs of immunocompromised
patients, a combined
opportunistic inflammatory disease such as
P. carinii pneumonia should be
considered in the diagnosis.
1712. Authors
Meral A.
Sevinir B. Gunay U.
Title
Efficacy of immunization against hepatitis B
virus infection in children
with cancer.
Source
Medical & Pediatric Oncology. 35(1):47-51, 2000 Jul.
Abstract
BACKGROUND: The purpose of this study was to
evaluate the impact of
hepatitis B prophylaxis in preventing
hepatitis B infection in children
with malignancy. PROCEDURE: Between May,
1993, and September, 1998, a
total of 151 children (95 boys, 56 girls),
29 (19%) with lymphoma, 58
(39%) with leukemia, and 64 (42%) with solid
tumor, were screened for
hepatitis B virus (HBV). The mean age was 7.
5 +/- 2.5 years. Children
with negative serology received active
and/or passive immunization. HBsAg
and anti-HBs were positive prior to
vaccination in 16 (10%) and 17 (11%)
children, respectively. One hundred eighteen
children (78%) of one hundred
fifty-one with negative serology were
included in the vaccination program.
The vaccine dose was 40 &mgr;g. Children
with solid tumor and lymphoma
received recombinant hepatitis B vaccine at diagnosis, repeated at
months
1, 2, and 12. Hyperimmunglobulin was
administered monthly in children with
leukemia during the intensive chemotherapy
period. They were then
vaccinated following the third month of
maintenance therapy with the
schedule described above. Anti-HBs titers
were measured every 3 months,
and titers above 10 mlU/ml were accepted as
protective. RESULTS: Anti-HBs
positivity after the first three doses was
77% in solid tumors, 88% in
acute leukemia, and 48% in lymphomas.
Anti-HBs positivity with respect to
diagnosis in children completing the
vaccination schedule was 94% in solid
tumor, 90% in leukemia, and 74% in lymphoma
(P > 0.05). Thirty-three
percent of children have not received the
fourth dose as yet. In total 78%
of the children developed protective
antibody titers with or without the
fourth dose, and none was infected with HBV
during 3 years of follow-up.
Ten (39%) of twenty-six children who
remained unresponsive to immunization
were infected with HBV. CONCLUSIONS: These
data reveal that HBV
prophylaxis is necessary and that our
vaccination schedule is effective in
preventing HBV infection in these children.
Copyright 2000 Wiley-Liss,
Inc.
1713. Authors
Merican I.
Title
Screening for hepatocellular carcinoma.
Source
Medical Journal of Malaysia. 51(1):12-7, 1996 Mar.
Abstract
Hepatocellular carcinoma (HCC) is one of the
commonest cancers in Asian
males. In Malaysia, it is one of the ten
most common cancers amongst the
male population. Most of our patients with
HCC present to us rather late
and almost all die within 4 months of
diagnosis. HCC occurs more commonly
in patients with cirrhosis associated with
hepatitis B and C infections.
Screening for HCC can lead to early
detection of small tumours (< 5 cm)
that are more amenable to surgical
resection, resulting in improved
survival rates. The average 5-year survival
rate for those who have
undergone surgical resection is 68% (range,
22-73%). Better results are
obtained with the smaller tumours (< 2 cm
in diameter). Patients with
chronic hepatitis B and C infection
especially those who are > 45 years of
age, who have concomitant cirrhosis or have
a family history of HCC should
be examined every 3-6 months with periodic
serum alpha-fetoprotein (AFP)
measurements and abdominal ultrasound
examinations. Abdominal ultrasound
is useful in the detection of small tumours.
While mass screening for HCC
is not cost-effective in countries of low
incidence of HCC, screening of
high risk groups may be justified in
countries with a high endemicity of
HBV infection. Screening for HCC in Japan,
Taiwan and China appears to
yield better results than those in the West.
Nonetheless, primary
prevention with mass hepatitis B vaccination
and blood donor screening for
anti-HCV is expected to make a much greater
impact in the control of HCC
in the years to come.
1714. Authors
Milkiewicz P. Saksena S. Hubscher
SG. Elias E.
Title
Wilson's disease with superimposed
autoimmune features: report of two
cases and review. [Review] [17 refs]
Source
Journal of Gastroenterology &
Hepatology. 15(5):570-4, 2000 May.
Abstract
We describe two females, 15 and 23 years
old, respectively, who presented
with classical features of Wilson's disease
(WD) and several features of
autoimmune hepatitis (AIH). The first
patient was initially diagnosed as
AIH and treated with prednisolone which
caused clinical improvement, with
an increase of serum albumin from 22 to 30
g/L, and a decrease of
aspartate aminotransferase from 103 to 47
U/L. Subsequent diagnosis of WD
and introduction of penicillamine gave
excellent improvement and complete
normalization of liver function tests. The
second patient, at first also
diagnosed as having AIH, was treated with
steroids and azathioprine with
initial improvement, but subsequent
deterioration. The diagnosis of WD was
made 2 years after initial diagnosis of AIH,
as the patient reached
end-stage liver disease and required a
transplant. Therefore,
d-penicillamine treatment was not attempted.
We conclude that, in patients
with AIH, a thorough screening for WD is
necessary, particularly when the
response to steroid therapy is poor.
Conversely, in patients suffering
from WD with superimposed features of AIH, a
combination of steroids and
penicillamine may be of benefit.
[References: 17]
1715. Authors
Minutello M. Zotti C. Orecchia S. Di Martino E. Bastianoni I. Ypma E.
Ruggenini Moiraghi A. Podda A.
Title
Dose range evaluation of a new inactivated
hepatitis A vaccine
administered as a single dose followed by a
booster.
Source
Vaccine.
19(1):10-5, 2000 Aug 15.
Abstract
A total of 242 healthy adults were immunised
with a first dose of an
investigational inactivated hepatitis A
vaccine. Three concentrations (3,
6 and 12 EU [ELISA units]) of the
experimental vaccine were used and
compared to a licensed reference vaccine.
The aim was to determine the
antigenic concentration of the study vaccine
inducing the highest
seroconversion rate and anti-Hepatitis A
virus (HAV) antibody response at
2 weeks after the primary immunisation. A
booster dose was given at month
6. At 15 days after the primary immunisation
the seroconversion rates in
subjects vaccinated with the 6 and 12 EU
vaccines were 78 and 94%,
respectively. At 30 and 180 days after the
primary immunisation the
percentages of seropositivity were 100% for
both groups. The antibody
response to the 12 EU study vaccine was
similar to that to the reference
vaccine. The percentages of seropositivity
at 15 and 180 days after the
primary immunisation were 94 vs 93%, and 100
vs 93% in the experimental
and reference vaccine respectively. Thus,
because it induces early and
lasting seroconversion, the 12 EU study
vaccine seems to be the most
effective as a high potency HAV vaccine.
1716. Authors
O'Beirne J.
Patch D. Holt S. Hamilton M.
Burroughs AK.
Title
Alcoholic hepatitis-the case for intensive
management. [Review] [18 refs]
Source
Postgraduate Medical Journal. 76(898):504-7, 2000 Aug.
Abstract
Alcoholic hepatitis is a common condition
with a high mortality. Although
treatment options for established alcoholic
hepatitis are limited, many of
the complications of this condition are
preventable. This case report and
discussion illustrate the important role of
early diagnosis and
intervention in this patient group.
Important management points are
stressed to aid physicians who may encounter
this condition rarely.
[References: 18]
1717. Authors
Ohta A.
Sekimoto M. Sato M. Koda T.
Nishimura S. Iwakura Y. Sekikawa
K.
Nishimura T.
Title
Indispensable role for TNF-alpha and
IFN-gamma at the effector phase of
liver injury mediated by Th1 cells specific
to hepatitis B virus surface
antigen.
Source
Journal of Immunology. 165(2):956-61, 2000 Jul 15.
Abstract
We report the development and
characterization of a novel model of severe
hepatitis induced against hepatitis B virus
surface Ag (HBsAg). HBsAg was
successfully targeted into the liver in
soluble form. Using this unique
property of HBsAg, we established a liver
injury model induced by
HBsAg-specific Th1 cells. Severe liver
injury was induced in C57BL/6 mice
by injection of HBsAg together with
HBsAg-specific Th1 cells.
Histochemical examination demonstrated
extensive necroinflammatory hepatic
lesions in these animals. Application of
this liver injury model to mutant
or gene knockout mice enabled us to define
the effector mechanisms of Th1
cells in fulminant hepatitis. When
Fas-deficient lpr mice were used as
recipients, a similar degree of liver injury
was induced as in wild-type
mice. Moreover, HBsAg-specific Th1 cells
obtained from perforin-/- mice
could induce severe liver injury in both
wild-type and lpr mice. These
results indicated that neither Fas ligand
nor perforin are essential for
Th1-mediated liver injury in this model.
Pretreatment with anti-TNF-alpha
mAb prevented liver injury, whereas severe
liver injury was induced in
TNF-alpha-/- mice. Moreover, IFN-gamma
receptor-deficient mice were
resistant to Th1-mediated liver injury.
Therefore, TNF-alpha and
IFN-gamma, which were produced by
HBsAg-specific Th1 cells during the
effector phase, appeared to be indispensable
in the pathogenesis of
fulminant hepatitis.
1718. Authors
OiConnor JA.
Title
Acute and chronic viral hepatitis. [Review]
[30 refs]
Source
Adolescent Medicine. 11(2):279-92, 2000 Jun.
Abstract
Viral hepatitis is the most common cause of
acute and chronic hepatitis.
The term viral hepatitis generally refers to
infections resulting from one
of the hepatotrophic viruses: hepatitis A,
B, C, D, and E. The last 10
years have brought many important advances
in understanding the
epidemiology, pathogenesis, molecular
biology, and immunoprophylaxis of
infections caused by hepatotrophic viruses.
Development of sensitive and
specific immunoassays has enabled detection
of specific agents. This has
allowed for identification of infected
patients and monitoring response to
therapy. Additionally, serologic markers
have allowed for isolation of
contaminated blood products and a reduction
in the spread of disease. The
remaining challenge is the application of
this knowledge to the treatment
and prevention of viral hepatitis. This
article explores the risk factors,
epidemiology, microbiology, clinical and
laboratory diagnosis, treatment,
and prevention of the hepatotrophic viral
infections. [References: 30]
1719. Authors
Par A.
Title
Diagnosis and management of chronic
hepatitis C. [Review] [33 refs]
Source
Canadian Journal of Gastroenterology. 14 Suppl B:83B-88B, 2000 Jul-Aug.
Abstract
This mini-review is devoted to the main
questions of diagnosis, treatment
and prevention of chronic hepatitis C (CHC).
Diagnosis of CHC is based on
virological, biochemical and histological
findings. The etiology of CHC
should be proven by the presence of antibody
to hepatitis C virus
(anti-HCV) and detection of viral nucleic
acid (HCV RNA), using
qualitative and quantitative polymerase
chain reaction or branched chain
DNA techniques. Serum aminotransferase
levels can reflect the biochemical
activity of liver disease, while biopsy is
very important in the grading
and staging of the pathological process. The
generally accepted treatment
of CHC is interferon (IFN); however,
recently, the combination of IFN with
the oral nucleoside analogue ribavirin has
become the therapy of choice,
not only for relapsers but also for naive
patients. Prevention of
hepatitis C by vaccination is not yet
available. Screening blood donors
and members of high risk groups, as well as
ensuring good public health
measures, are imperative to inhibit the
spread of HCV. [References: 33]
1720. Authors
Roca B. Gomez CJ.
Arnedo A.
Title
Adherence, side effects
and efficacy of stavudine plus lamivudine plus
nelfinavir in treatment-experienced
HIV-infected patients.
Source
Journal of Infection. 41(1):50-4, 2000 Jul.
Abstract
OBJECTIVES: To evaluate adherence, side
effects and efficacy of a modality
of highly active antiretroviral therapy
(HAART) in HIV-infected patients.
METHODS: In a cohort, prospective study, 65
previously treated patients
received stavudine plus lamivudine plus
nelfinavir. Fifty-three
participants (81%) had a history of
intravenous drug use. Patients were
evaluated at 3-month intervals. The
association of adherence with
demographic variables, hepatitis C virus
infection, number of stopped
antiretroviral regimens, HIV RNA level, CD4
cell count, and adverse
effects to drugs was assessed. RESULTS:
After a median follow-up of 12
months, 30 participants (46%) showed
adequate adherence in all visits. An
association was observed between adherence
and female sex: 18 of 47 men
(38%) vs. 12 of 18 women (67%) presented
adequate adherence in all visits
(P=0. 0416). An association was also
observed between adherence and low
baseline HIV RNA level (P=0.0229).
Discontinuation of treatment took place
because of refusal to take medication in 11
participants (17%) and because
of side effects in seven participants (11%).
Undetectable HIV RNA level
was achieved in 26 patients (40%) at 3
months and in lower percentages at
months 6, 9 and 12. CONCLUSIONS: Overall
adherence to the employed HAART
regimen was poor. Female sex and low
baseline HIV RNA were associated with
better adherence. Refusal to take
medications and side effects were the
main reasons to stop therapy. At 3 months'
follow-up, virological efficacy
was achieved in 40% of patients. Copyright
2000
1721. Authors
Roeckel IE.
Title
Commentary: Iron metabolism in hepatitis C
infection. [Review] [11 refs]
Source
Annals of Clinical & Laboratory
Science. 30(2):163-5, 2000 Apr.
Abstract
Hepatitis C virus (HCV) infections have
started to decline, but up to
10,000 deaths each year are the consequence
of chronic liver disease,
following the infection. Laboratory testing
identifies HCV-infected
individuals using positive recombinant
immunoblot assays to detect the
presence of the antibody; the diagnosis is
confirmed by detecting HCV RNA
in serum. HCV-infected patients who have
large accumulations of hepatic
iron have not responded well to interferon
therapy, compared to patients
with normal hepatic iron stores. Physicians
who treat patients infected
with HCV should be aware of the detrimental
effect of excess liver iron on
interferon therapy. The degree of hepatic
iron overload should be assessed
and the reason for the excess iron should be
investigated. Phlebotomy is
the most practical method for iron removal
and is well tolerated by
patients with HCV infection. [References:
11]
1722. Authors
Rosen HR.
Gretch D. Kaufman E. Quan S.
Title
Humoral immune response to hepatitis C after
liver transplantation:
assessment of a new recombinant immunoblot
assay.
Source
American Journal of Gastroenterology. 95(8):2035-9, 2000 Aug.
Abstract
OBJECTIVE: The immune control of infection
with hepatitis C virus (HCV) is
poorly understood; vigorous antibody
responses to viral proteins seem to
coexist with the virus and thus whether they
are neutralizing remains
controversial. HCV-related liver failure is
the leading indication for
orthotopic liver transplantation (OLT)
worldwide. Attenuated antibody
responses in immunosuppressed patients and
decreased reliability compared
to assessment of HCV RNA has hampered the
use of antibody testing
post-OLT. The goals of this current analysis
were twofold: to determine
the sensitivity of a prototype strip
immunoblot assay (RIBA 3.0, Chiron
Diagnostics) for the diagnosis of HCV
post-OLT; to determine if there was
a correlation between antibody response and
severity of histological
recurrence. METHODS: The study was comprised
of 76 HCV-positive
individuals divided into three patient
groups: liver allograft recipients
with evidence of mild or no histological
recurrence (n = 52), liver
allograft recipients with evidence of severe
HCV recurrence and allograft
cirrhosis (n = 12), and nontransplant
patients being enrolled in an
induction interferon trial (n = 12). All
transplant patients had
histological follow-up of at least 1 yr.
RESULTS: Sixty of the 64 (94%)
HCV-positive OLT recipients had 1+ reactivity
to two or more recombinant
antigens; three of the patients who lacked a
detectable response had
minimal histological recurrence and one had
severe recurrence. All
nontransplant patients demonstrated 4+
reactivity to at least two
antigens, and 55/64 (86%) OLT recipients
demonstrated this same level of
reactivity. Seven of the nine patients
lacking this high level of
reactivity had evidence of minimal
recurrence. Furthermore, the mean (+/-
SEM) level of antibody reactivity for c100
(p = 0.04) and NS5 (p = 0.01)
were significantly lower for patients with
mild recurrence after OLT,
compared to the other groups. The level of
antibody reactivity was
unrelated to HCV genotype or viral load.
CONCLUSIONS: The recently
developed RIBA 3.0 assay for detection of
antibodies to HCV appears to be
highly sensitive for the diagnosis of HCV
post-OLT. In general, the level
of antibody reactivity was comparable in the
transplant patients and in
nonimmunosuppressed controls. The pathogenic
implications of the
relatively diminished humoral response in
patients with mild recurrence
post-OLT are discussed.
1723. Authors
Roubalova K. Suchankova A. Vitek
A. Sajdova J.
Title
Presence of herpes simplex virus (HSV) in
peripheral leukocytes of patient
who developed active HSV infection after
bone marrow transplantation.
Source
Journal of Clinical Virology. 17(1):37-42, 2000 Jun.
Abstract
BACKGROUND: Despite of prophylactic
antiviral therapy, latent HSV may be
reactivated in bone marrow transplant (BMT)
recipients and cause serious
disease. Rapid diagnosis of HSV infection is
needed to prompt institution
of appropriate therapy. OBJECTIVES: We
report a case of the allogenic BMT
recipient, who developed ulcerative
esophagitis which progressed to
generalized HSV infection and graft versus
host reaction (GVHR).We
consider several diagnostic approaches to
detection of active HSV
infection in this patient. STUDY DESIGN:
Polymerase chain reaction (PCR)
was used to detect HSV DNA in esophageal
biopsy specimens and peripheral
leukocytes (PBL). Isolation of HSV in tissue
culture was performed to
prove infectious virus in swabs from
mucocutaneous lesions or in PBL.
RESULTS: Using PCR, HSV DNA was detected in
peripheral leukocytes of the
patient who had developed generalized HSV
infection accompanied with
hepatosplenomegaly and hepatitis. At that
time, a fully infectious
ACV-resistant HSV was isolated from his PBL.
On the other hand, HSV DNA
was not detected in PBL of other
BMT-recipients with skin- or
organ-localized infection. CONCLUSIONS:
Presence of HSV-DNA in PBL of BMT
recipients can signalize generalized HSV
infection. Isolation of HSV from
PBL by cocultivation with human fibroblasts
can be used as an alternative
diagnostic approach in these patients.
1724. Authors
Schmitt HJ.
Knuf M. Ortiz E. Sanger R.
Uwamwezi MC. Kaufhold A.
Title
Primary vaccination of infants with
diphtheria-tetanus-acellular
pertussis-hepatitis B virus- inactivated
polio virus and Haemophilus
influenzae type b vaccines given as either
separate or mixed injections
[see comments].
Source
Journal of Pediatrics. 137(3):304-12, 2000 Sep.
Abstract
OBJECTIVE: The aim of this open,
multicenter, randomized trial was to
evaluate the immunogenicity and
reactogenicity of a candidate combined
diphtheria-tetanus-acellular
pertussis-hepatitis B virus-inactivated polio
virus (DTaP-HBV-IPV) vaccine when given as
either a mixed or as separate
concomitant injections with Haemophilus
influenzae type b (Hib) vaccine.
STUDY DESIGN: A total of 359 subjects were
randomized to receive either
DTaP-HBV-IPV/Hib (mixed administration - 180
subjects) or DTaP-HBV-IPV +
Hib (separate administration in opposite
limbs - 179 subjects) at 2, 3,
and 4 months of age. RESULTS: After
vaccination, seroprotective antibody
concentrations against diphtheria, tetanus,
hepatitis B, and polio viruses
and a high (> or = 97%) pertussis vaccine
response were seen in almost all
study participants. All subjects except one
in the mixed administration
group had postvaccination Hib anti-PRP
antibody concentrations > or = 0.15
microg/mL. Of subjects in the mixed and
separate group, 77.2% (geometric
mean antibody concentration, 2. 62
microg/mL) and 88.6% (geometric mean
antibody concentration, 4.45 microg/mL) had
Hib anti-PRP concentrations >
or = 1 microg/mL, respectively. The addition
of the Hib component to the
5-component vaccine did not increase the
incidence of local or general
reactions. CONCLUSION: Both administrations
of the candidate vaccine were
found to be safe, immunogenic, and well
tolerated. Although anti-PRP
geometric mean antibody concentrations and
the percent of subjects
achieving the 1 microg/mL seroprotective
level were lower after the mixed
administration, they were in the range seen
with monovalent Hib vaccines
or with other DTaP-based/Hib combinations
licensed in some European
countries. Therefore both administrations
have the potential to simplify
childhood immunization.
1725. Authors
Seeto RK.
Fenn B. Rockey DC.
Title
Ischemic hepatitis: clinical presentation
and pathogenesis.
Source
American Journal of Medicine. 109(2):109-13, 2000 Aug 1.
Abstract
BACKGROUND: The pathophysiology of ischemic
hepatitis, otherwise known as
"shock liver," is poorly
understood, although it is believed to be the
result of a reduction in systemic blood flow
as typically occurs in shock.
The aim of this study was to investigate the
importance of this phenomenon
as well as other clinical features in
patients with ischemic
hepatitis.METHODS: We identified a cohort of
31 patients (case group) who
met the most commonly accepted definition of
ischemic hepatitis (an acute
reversible elevation in either the serum
alanine or aspartate
aminotransferase level of at least 20 times
the upper limit of normal,
excluding known causes of acute hepatitis or
hepatocellular injury, in an
appropriate clinical setting). We also
evaluated the clinical features and
serum aminotransferase levels in a cohort
(the control group) of 31
previously healthy patients who sustained
major nonhepatic trauma at San
Francisco General Hospital, a major trauma
center. Both groups of patients
had documented systolic blood pressures
<75 mm Hg for at least 15 minutes.
Clinical and hemodynamic (invasive and
noninvasive) data were
recorded.RESULTS: Despite the marked
reduction in blood pressure, no
patient in the control group developed
ischemic hepatitis. The mean (+/-
SD) peak serum aspartate aminotransferase
level in the control group was
only 78 +/- 72 IU, in contrast with a mean
peak of 2,088 +/- 2,165 IU in
the case group. All 31 patients with
ischemic hepatitis had evidence of
underlying organic heart disease, 29 (94%)
of whom had right-sided heart
failure.CONCLUSIONS: Systemic hypotension or
shock alone did not lead to
ischemic hepatitis in any patient. The vast
majority of patients with
ischemic hepatitis had severe underlying
cardiac disease that had often
led to passive congestion of the liver.
These data lead us to propose that
right-sided heart failure, with resultant
hepatic venous congestion, may
predispose the liver to hepatic injury
induced by a hypotensive event.
1726. Authors
Seltsam A.
Shukry-Schulz S. Salama A.
Title
Vaccination-associated immune hemolytic
anemia in two children.
Source
Transfusion. 40(8):907-9, 2000 Aug.
Abstract
BACKGROUND: Two children in whom acute
autoimmune hemolytic anemia (AIHA)
developed after vaccination were studied.
CASE REPORTS: The children were
a 20-month-old girl and a 21-month-old boy.
The diagnosis of AIHA was made
in accordance with established criteria
(hemolysis, positive DAT, and lack
of other reasons for the hemolysis).
Serologic tests were performed
according to standard technique. RESULTS:
The girl experienced two attacks
of hemolysis. The first episode occurred 2
weeks after oral polio
vaccination, and the second episode was
observed 7 months later, when she
received a simultaneous vaccination against
mumps, rubella, and measles.
The DAT was strongly positive with anti-C3d.
No autoantibodies were
detectable in either episode. The boy
experienced acute hemolysis a few
days after a simultaneous revaccination
against
diphtheria-pertussis-tetanus, Haemophilus
influenzae, hepatitis B, and
polio. The DAT using anti-IgG was strongly
positive, and the DAT performed
with anti-C3d was weakly positive.
CONCLUSION: Vaccination-induced AIHA
resembles those forms of AIHA related to
infectious diseases, and it may
occur more frequently than has been
reported.
1727. Authors
Stevens AB.
Coyle PV.
Title
Hepatitis C virus: an important occupational
hazard?. [Review] [74 refs]
Source
Occupational Medicine (Oxford). 50(6):377-82, 2000 Aug.
Abstract
Infection with Hepatitis
C virus (HCV) is estimated to affect 3% of the
world's population and is an important cause
of liver disease. It is most
commonly transmitted by percutaneous
exposure. Although current evidence
does not suggest an increased prevalence of
HCV infection among healthcare
workers, transmission of infection following
occupational exposure has
been demonstrated. An average transmission
rate of 1.8%, following
percutaneous injury, has been reported. The
risk of transmission is higher
from patients with viraemia, as measured by
a positive polymerase chain
reaction for HCV RNA. After exposure to HCV,
healthcare workers should be
actively followed up, initially using a test
to detect viral RNA. This may
facilitate earlier diagnosis and treatment.
Recent reports in the UK, of
transmission of infection to patients from
HCV infected healthcare
workers, have prompted a review of the
appropriateness of HCV infected
individuals undertaking exposure prone
procedures. [References: 74]
1728. Authors
Strassburg CP. Manns MP.
Title
Autoimmune tests in primary biliary
cirrhosis. [Review] [80 refs]
Source
Best Practice & Research in Clinical
Gastroenterology. 14(4):585-99, 2000
Aug.
Abstract
Primary biliary cirrhosis (PBC) is
characterized by an immune mediated,
irreversible destruction of the small
intrahepatic bile ducts leading to
progressive liver cirrhosis and frequently
to liver failure. The course of
the disease is variable and an early
diagnosis is desirable to identify
individuals with rapidly progressing
disease, to initiate adequate
therapeutic measures and to evaluate the
necessity of liver
transplantation. Serological tests represent
the single most important
diagnostic feature of PBC because liver
histology, biochemistry, or
clinical syndrome alone are not reliable in
this respect. The molecular
definition of the autoantigen targets of
antimitochondrial antibodies
(AMA) has resulted in the development of
reproducible and effective
serological testing strategies. AMA directed
against the ketoacid
dehydrogenase complex are highly
disease-specific but not directed against
liver-specific target structures. Despite a
high disease specificity,
their usefulness for predicting the course
of disease, the timing of liver
transplantation, or disease recurrence after
transplantation is limited.
The realization that about 5% of patients
with PBC do not display AMA has
led to the identification of PBC-specific
antinuclear autoantibodies
directed against the nuclear pore complex
and other targets. The overlap
of PBC with autoimmune hepatitis and primary
sclerosing cholangitis
represents a diagnostic challenge in which
autoantibody determinations
play a central role and contribute to the
administration of suitable
treatment options. Copyright 2000 Harcourt
Publishers Ltd. [References:
80]
1729. Authors
Tanaka E.
Ohue C. Aoyagi K. Yamaguchi K. Yagi S. Kiyosawa K. Alter
HJ.
Title
Evaluation of a new enzyme immunoassay for
hepatitis C virus (HCV) core
antigen with clinical sensitivity
approximating that of genomic
amplification of HCV RNA.
Source
Hepatology.
32(2):388-93, 2000 Aug.
Abstract
The aim of this study was to analyze the
clinical performance of a new
enzyme immunoassay (EIA) for hepatitis C
virus (HCV) core antigen in
comparison with the reverse transcription
polymerase chain reaction
(RT-PCR). A total of 310 patients with acute
or chronic hepatitis C, and
132 HCV-negative controls were studied.
Chemiluminescence EIA with
monoclonal anti-HCV core antigen was used,
and qualitative and
quantitative commercial RT-PCRs and an
in-house nested RT-PCR were
performed. Compared with nested RT-PCR, the
core antigen assay showed 97%
sensitivity and 100% specificity in 75
patients with chronic hepatitis C
and 132 controls. HCV core antigen was
positive in 16 (94%) of 17 patients
with acute hepatitis C at initial
consultation. In 3 persons prospectively
followed, core antigen was detected in the
first available (1-3 weeks)
post-transfusion sample. In 167
anti-HCV-positive individuals, 129 (77%)
were viremic; core antigen was detected in
126 (98%) compared with 129
(100%) for nested RT-PCR and 121 (94%) for
the commercial RT-PCR. In 48
patients with chronic hepatitis C treated
with interferon alfa, the
concentration of core antigen before
treatment was significantly (P <.002)
lower in patients with sustained response
than in nonresponders. All
responders had a sustained loss of core
antigen, whereas all nonresponders
remained core antigen positive. The
concentrations of HCV core antigen and
HCV RNA correlated significantly (n = 48, r
=.627, P <.001). In
conclusion, the HCV core antigen assay is
useful for the diagnosis of
acute and chronic hepatitis C, and for
predicting and monitoring the
effect of interferon alfa treatment.
1730. Authors
Tanaka H.
Tsukuma H. Kasahara A. Hayashi N.
Yoshihara H. Masuzawa M.
Kanda T.
Kashiwagi T. Inoue A. Kato M.
Oshima A. Kinoshita Y. Kamada
T.
Title
Effect of interferon therapy on the
incidence of hepatocellular carcinoma
and mortality of patients with chronic
hepatitis C: a retrospective cohort
study of 738 patients.
Source
International Journal of Cancer. 87(5):741-9, 2000 Sep 1.
Abstract
The effect of interferon on the long-term
clinical outcome of patients
with chronic hepatitis C remains unclear.
This study included 594 patients
with chronic hepatitis C who received
interferon-alpha therapy (Interferon
group) and 144 patients with chronic
hepatitis C who did not receive
interferon (Control group). The patients in
the Interferon group were
classified into the following three groups
based on the response of the
serum aminotransaminase level of the patient
during and after completion
of the therapy protocol: sustained
responders (n = 175), transient
responders (n = 165), and non-responders (n
= 254). The age, sex, serum
aminotransaminase level, platelet count,
histological staging, hepatitis C
virus (HCV) subtype, and HCV concentration
at baseline were adjusted with
the Cox proportional hazards model. The
length of follow-up for assessment
of the risk for developing hepatocellular
carcinoma (HCC) was 57.2 +/-
13.9 months in the Interferon group and 67.7
+/- 28.7 months in the
Control group. Multivariate analysis showed
that interferon therapy
decreased the risk for developing HCC by 48%
compared with that in the
Control group (P = 0.064). The older the
age, being male, having a low
platelet count, and higher histological
stage were independent factors
associated with the development of HCC. The
hazard rate ratio for
development of HCC in the sustained
responders, transient responders, and
non-responders was 0.16 (95% confidence
interval [CI]: 0.04-0.62), 0.27
(95% CI: 0. 09-0.79), and 0.74 (95% CI:
0.37-1.48), respectively. During
follow-up, 18 patients in the Interferon
group died (10 from liver-related
diseases) and 17 patients in the Control
group died (10 from liver-related
diseases). No sustained responder or
transient responder in the Interferon
group died of liver-related disease. The
cumulative survival rates of the
Interferon and Control groups were nearly
identical during the first 5
years following diagnosis. Thereafter, the
cumulative survival rate of the
Control group declined, resulting in an
8-year survival rate in the
Interferon and Control groups of 97% and
81%, respectively (P = 0. 061).
Similar trends were seen in the survival
analysis of those who had died of
liver disease: the 8-year survival rates of
the Interferon and Control
groups were 98% and 88%, respectively (P =
0. 32). Our study demonstrated
that interferon therapy significantly
lowered the incidence of HCC among
patients with chronic hepatitis C who showed
sustained normalization and
among patients who showed transient
normalization of the serum
aminotransferase level after completion of
interferon therapy. The
survival analyses and determination of cause
of death suggested that
interferon therapy improves the long-term
survival of chronic hepatitis C
patients who respond to this therapy,
possibly by decreasing mortality
from liver-related diseases. Copyright 2000
Wiley-Liss, Inc.
1731.Authors
Teixeira R.
Pastacaldi S. Papatheodoridis
GV. Burroughs AK.
Title
Recurrent hepatitis C after liver
transplantation. [Review] [112 refs]
Source
Journal of Medical Virology. 61(4):443-54, 2000 Aug.
Abstract
Cirrhosis due to hepatitis C is now the
commonest indication for liver
transplantation in Western Europe and in the
United States. Graft
reinfection is almost universal. The natural
history of recurrent
hepatitis C ranges from minimal damage to
cirrhosis in a few months or
years. Different virus and host immune
factors are involved in the
pathogenesis of hepatitis and are
determinants of the outcome. The
association between immunosuppression and
severity of HCV recurrence is
conflicting and remains to be evaluated
fully. The treatment of recurrent
HCV disease with IFN or ribavirin, as
monotherapy, is ineffective.
Preliminary results from combination
therapy, however, are encouraging.
Currently, a reasonable approach would be to
treat patients with
histological and clinical disease
progression. New approaches for the
prophylaxis of recurrent hepatitis C are
under evaluation but whether this
treatment will influence the severity of
liver disease or the outcome of
recurrence is still unknown. Copyright 2000
Wiley-Liss, Inc. [References:
112]
1732. Authors
Thobe N.
Pilger P. Jones MP.
Title
Primary hypothyroidism masquerading as
hepatic encephalopathy: case report
and review of the literature. [Review] [13
refs]
Source
Postgraduate Medical Journal. 76(897):424-6, 2000 Jul.
Abstract
A 74 year old woman with hepatitis C of long
duration was admitted to
hospital in hyperammonaemic coma. Despite
aggressive treatment of hepatic
encephalopathy, there was no clinical
improvement. As part of her
evaluation for other causes of altered
mental status, she was found to be
profoundly hypothyroid. Treatment with
thyroid replacement hormone was
accompanied by prompt normalisation of her
mental status and
hyperammonaemia. Hypothyroidism may
exacerbate hyperammonaemia and
portosystemic encephalopathy in patients
with otherwise well compensated
liver disease. Hyopthyroidism should be
considered in the differential
diagnosis of encephalopathy in patients with
liver disease. [References:
13]
1733. Authors
Wang F.
Yoshida I. Takamatsu M. Ishido S.
Fujita T. Oka K. Hotta H.
Title
Complex formation between hepatitis C virus
core protein and
p21Waf1/Cip1/Sdi1.
Source
Biochemical & Biophysical Research
Communications. 273(2):479-84, 2000
Jul 5.
Abstract
The core protein (Core) of hepatitis C virus
(HCV) has been known to play
an important role in hepatocarcinogenesis.
By using glutathione
S-transferase (GST) pull-down assay, we show
here that Core formed a
complex with p21Waf1/Cip1/Sdi1 (p21) cell
cycle regulator. The
deletion-mapping analysis revealed that a
portion near the N-terminus of
Core (amino acids 24-52) and a C-terminal
portion of p21 (amino acids
139-164) were involved in the complex
formation. The complex formation was
not impaired by point mutations of p21 at
residues 147, 149, and 150,
which have been reported to abrogate
interaction of p21 with proliferating
cell nuclear antigen (PCNA), discriminating
the Core-binding sequence from
the PCNA-binding sequence. Due to the close
vicinity of the binding sites,
however, Core and PCNA competed with each
other when interacting with p21.
The distinct interaction between Core and
p21 may provide a new aspect to
the studies of HCV pathogenesis. Copyright
2000 Academic Press.
1734. Authors
Woo PC.
Tsoi HW. Leung HC. Wong LP.
Wong SS. Chan E. Yuen KY.
Title
Enhancement by ampicillin of antibody
responses induced by a protein
antigen and a DNA vaccine carried by
live-attenuated Salmonella enterica
serovar Typhi.
Source
Clinical & Diagnostic Laboratory
Immunology. 7(4):596-9, 2000 Jul.
Abstract
Live-attenuated Salmonella species are
effective carriers of microbial
antigens and DNA vaccines. In a mouse model,
the immunoglobulin M (IgM)
and total antibody levels directed toward
the lipopolysaccharide of
Salmonella enterica serovar Typhi were
significantly enhanced at day 21
after oral immunization with live-attenuated
serovar Typhi (strain Ty21a)
when ampicillin was concomitantly
administered (P < 0.05 and P < 0.005,
respectively). The heat-killed
Ty21a-stimulated lymphocyte proliferation
indices for the ampicillin group at day 21
were significantly higher than
those for the normal saline (NS) group (P
< 0.005, P < 0.001, and P <
0.01) for all three doses of antigen (10(4),
10(5), and 10(6) heat-killed
Ty21a per well, respectively). The 50%
lethal doses for mice from the
ampicillin and NS groups immunized with
Ty21a with pBR322 after wild-type
serovar Typhi challenge on day 24 were 3.4 x
10(7) and 5.0 x 10(6) CFU,
respectively. The fecal bacterial counts for
the ampicillin group at days
1, 3, and 5 were significantly lower than
those for the NS group (P <
0.01, P < 0.01, and P < 0.05,
respectively), and there was a trend toward
recovery of Ty21a in a larger number of mice
from the ampicillin group
than from the NS group. Furthermore, the
IgG2a levels directed toward
tetanus toxoid were significantly enhanced
at days 7 and 21 after oral
immunization with Ty21a that carried the
fragment c of tetanus toxoid when
ampicillin was concomitantly administered (P
< 0.05 and P < 0.005,
respectively), and the IgM and total
hepatitis B surface antibody levels
were significantly enhanced at days 7 (P
< 0.005 and P < 0.05,
respectively) and 21 (P < 0.01 and P <
0.05, respectively) after oral
immunization with Ty21a that carried the DNA
vaccine that encodes
hepatitis B surface antigen when ampicillin
was concomitantly
administered. The present observation may
improve the efficacy of the
protein antigens and DNA vaccines carried in
live-attenuated bacteria, and
further experiments should be carried out to
determine the best
antibiotics and dosage regimen to be used,
as well as the best carrier
system for individual protein antigens and
DNA vaccines.
1735. Authors
Yamaguchi N. Tokushige K. Yamauchi
K. Hayashi N.
Title
Humoral immune response in Japanese acute
hepatitis patients with
hepatitis C virus infection.
Source
Canadian Journal of Gastroenterology. 14(7):593-8, 2000 Jul-Aug.
Abstract
The humoral immune response to acute
infection by hepatitis C virus (HCV)
is not yet perfectly clear in terms of
immunoglobulin (Ig) response,
diversity of HCV antigen, and the relation
with hepatitis severity and
antibody response. Serum IgM and IgG
anti-HCV levels in patients with HCV
and either acute hepatitis (AH) or fulminant
hepatitis (FH) were
investigated; the diversity of HCV antigen
was investigated by RIBA test
III. Of 22 AH patients, 12 (54.5%) were positive
for IgM anti-HCV, mainly
reacting to HCV core protein. The mean
interval until the appearance of
IgM anti-HCV after onset was 24.1+/-26.2
days. IgG anti-HCV mainly reacted
to both core and NS-3 antigen, appearing
42.6+/-42.1 days after onset.
From
a serial study of 15 AH patients, it was considered that in seven AH
patients (46. 7%), the IgM response would
precede the IgG response. In
another two AH patients, IgM anti-HCV was
not detected during the acute
disease phase. Of 48 chronic hepatitis
patients with HCV-RNA, 40 patients
were positive for IgM anti-HCV. Therefore,
IgM anti-HCV was useful for
diagnosis in some of the AH patients, but it
was difficult to use for
distinguishing between acute and chronic
infection. All four FH patients
with HCV-RNA were positive for both IgM and
IgG antibody to HCV at onset.
Their antibody titres were higher than those
of AH patients. These results
suggested that, as in FH due to HBV, FH due
to HCV could induce strong and
rapid humoral immunity.
1736. Authors
Zeuzem S.
Title
Gut-liver axis. [Review] [301 refs]
Source
International Journal of Colorectal
Disease. 15(2):59-82, 2000 Apr.
Abstract
The gut and the liver are the key organs in
nutrient absorption and
metabolism. Bile acids, drugs, and toxins
undergo extensive enterohepatic
circulation. Bile acids play a major role in
several hepatic and
intestinal diseases. Endotoxins deriving
from intestinal Gram-negative
bacteria are important in the pathogenesis
of liver and systemic diseases.
Chronic liver diseases can influence
gastrointestinal motility, which
together with other factors may contribute
to bacterial overgrowth and in
patients with ascites to an increased risk
of spontaneous bacterial
peritonitis. Patients with end-stage liver
disease frequently develop
portal hypertension leading to varices,
gastric vascular ectasia, and
portal hypertensive gastroenteropathy.
Several liver and biliary
abnormalities are observed in patients with
inflammatory bowel disease
(primary sclerosing cholangitis, autoimmune
hepatitis, cholelithiasis).
The primary defect in hemochromatosis is
located in the intestine, causing
an inappropriate increase in iron
absorption, and the liver is the site of
earliest and heaviest iron deposition.
Elevated transaminases are observed
in many patients with celiac disease, and
steatohepatitis frequently
develops in patients with jejunoileal bypass
and short bowel syndrome.
Furthermore, the liver is the primary organ
for metastasis of intestinal
cancer. Many viral, bacterial, fungal, and
parasitic diseases affect the
intestine as well as the liver and the
biliary tract. [References: 301]
2189.
Bilezikci B. Haberal AN.
Demirhan B.
Title
Hepatocyte growth factor in patients with
three different stages of
chronic liver disease including
hepatocellular carcinoma, cirrhosis and
chronic hepatitis: an immunohistochemical
study.
Source
Canadian Journal of Gastroenterology. 15(3):159-65, 2001 Mar.
Abstract
BACKGROUND AND AIMS: The specific role of
hepatocyte growth factor in
liver disease is unknown. The presence and
density of this factor in
patients with three different stages of
liver disease were investigated,
with the aim of assessing its prognostic
significance. PATIENTS AND
METHODS: Liver specimens from patients with
chronic hepatitis (n=20),
cirrhosis (n=20), hepatocellular carcinoma
(n=30) and normal livers (n=20)
were immunohistochemically stained to
determine the presence and density
of hepatocyte growth factor. RESULTS: There
were significantly more
hepatocyte growth factor-positive Kupffer
and Ito cells in all three
diseased groups than in the control group.
Also, there was significantly
more positive staining in chronic hepatitis
specimens than in specimens
from the cirrhosis, hepatocellular carcinoma
and control groups (P<0.05).
The hepatoma cells in 10 of the
hepatocellular carcinoma cases stained
positive, but none of the hepatocytes in the
chronic hepatitis, cirrhosis
and normal liver specimens stained. It was
only possible to assess
nonmalignant hepatocytes adjacent to the
hepatocellular carcinoma in the
four resection specimens, and no staining
for hepatocyte growth factor was
observed in these areas. There was no statistical
association between
density of hepatocyte growth factor and
histological activity index in
chronic hepatitis, or between density of
hepatocyte growth factor and
grade of hepatocellular carcinoma.
CONCLUSIONS: Similar to some previous
reports, this study revealed that hepatoma
cells can also express this
growth factor. Immunohistochemical detection
of hepatocyte growth factor
may prove to be a useful method of
diagnosing hepatocellular carcinoma in
challenging cases.
2190.
Chan AY. Dieckhaus KD. Ramsey WH.
Title
Cytomegalovirus hepatitis in a nontransplant
patient with autoimmune
hepatitis taking immunosuppressants.
Source
American Journal of Gastroenterology. 96(1):262-3, 2001 Jan.
2191.
High KA.
Title
Gene transfer as an approach to treating
hemophilia. [Review] [70 refs]
Source
Circulation Research. 88(2):137-44, 2001 Feb 2.
Abstract
Hemophilia is an X-linked bleeding diathesis
caused by a deficiency of
either factor VIII or factor IX. Present
treatment for hemophilia involves
intravenous infusion of either recombinant
or plasma-derived clotting
factor concentrates. Problems with this
treatment method, including the
expense, need for intravenous access, and
risks of blood-borne disease
transmission, have fueled an interest in
developing a gene-transfer
approach to treatment. On the basis of
experience with protein concentrate
therapy, it seems likely that even modest
elevations in circulating levels
of factor VIII or factor IX can prevent most
of the mortality and much of
the morbidity associated with the disease.
Hemophilia has a number of
advantages as a model system for working out
strategies for gene transfer
as an approach to the treatment of genetic
diseases; these include wide
latitude in choice of target tissue, a wide
therapeutic window for levels
of circulating factor, ease of determining
therapeutic endpoints, and
existence of excellent animal models of the
disease. Preclinical studies
over the last decade have recently
culminated in the initiation of
clinical trials of gene transfer for
hemophilia A and B. Three trials,
each using different vectors and target
tissues, are presently underway,
and two additional trials are in late
planning stages. This report reviews
the preclinical data underlying these
strategies and the design of the
ongoing and proposed clinical trials.
[References: 70]
2192.
Kato Y. Nakata K.
Omagari K. Kusumoto Y. Mori I.
Furukawa R. Tanioka
H.
Tajima H. Yano M. Eguchi K.
Title
Clinical features of fulminant hepatitis in
Nagasaki Prefecture, Japan.
Source
Internal Medicine. 40(1):5-8, 2001 Jan.
Abstract
OBJECTIVE: Fulminant hepatitis is a rare but
fatal disease. In the present
study, we examined the changes in etiology
and prognosis of fulminant
hepatitis in Nagasaki Prefecture, Japan
between 1980 to 1999. METHODS:
Eighty-one patients with fulminant hepatitis
admitted to our hospitals
from 1980 to 1999 were examined with respect
to the etiology and
prognosis. RESULTS: Fulminant hepatitis was
due to hepatitis A virus in 2
(12%) cases, hepatitis B virus in 18 (22%)
cases, unknown etiology in 50
(62%) cases, and drug-induced in 11(14%)
cases. The number of cases in the
first half of the study (1980-1989) was 47
and that of the latter half
(1990-1999) was 34 cases. The incidence of
fulminant hepatitis type B also
decreased from 14 cases (30%) to 4 cases
(12%) during these periods. The
overall survival rate of fulminant hepatitis
was 32%; it was equal in
fulminant hepatitis type B, fulminant
hepatitis of unknown etiology and
fulminant drug-induced hepatitis. The
survival rate of fulminant hepatitis
type A was 100%, though only two cases were
identified. Retrospectively,
the survival rate in patients with a
pre-encephalopathy period of < or =
10 days and aged < or = 39 years was
significantly higher than in patients
> or = 40 years of age (p<0.01). There
was no difference between the two
age groups when pre-encephalopathy period
was > or = 11 days. CONCLUSIONS:
The incidence of fulminant hepatitis
especially that of fulminant
hepatitis type B in Nagasaki Prefecture has
decreased in recent years. The
survival rate is significantly higher in
younger patients with a short
pre-encephalopathy period.
2193.
Malik AH. Collins RH Jr. Saboorian MH. Lee WM.
Title
Chronic graft-versus-host disease after
hematopoietic cell transplantation
presenting as an acute hepatitis.
Source
American Journal of Gastroenterology. 96(2):588-90, 2001 Feb.
Abstract
A variety of illnesses involving the gut and
liver follow hematopoietic
cell transplantation (HCT). A 20 yr-old
white male developed severe acute
hepatitis 36 wk (day 252) after matched,
unrelated, allogeneic HCT for
chronic myelogenous leukemia (CML). Mild
skin graft-versus-host disease
(GVHD) had occurred at about 20 wk (day 140)
after transplant. Liver
biopsy showed bile duct injury and a diffuse
lobular injury pattern most
consistent with a GVHD variant and not
reminiscent of drug-induced or
viral hepatitis. No findings suggestive of
herpesvirus, adenovirus, or
varicella-zoster virus were found. High-dose
steroids resulted in marked
improvement of his liver enzyme levels. We
report this patient as
representing the acute hepatitic presentation
of chronic GVHD of the
liver.
2194.
Neubauer K. Saile B.
Ramadori G.
Title
Liver fibrosis and altered matrix synthesis.
[Review] [75 refs]
Source
Canadian Journal of Gastroenterology. 15(3):187-93, 2001 Mar.
Abstract
Liver fibrosis represents the uniform
response of liver to toxic,
infectious or metabolic agents. The process
leading to liver fibrosis
resembles the process of wound healing,
including the three phases
following tissue injury: inflammation,
synthesis of collagenous and
noncollagenous extracellular matrix
components, and tissue remodelling
(scar formation). While a single liver
tissue injury can be followed by an
almost complete restitution ad integrum, the
persistence of the original
damaging noxa results in tissue damage.
During the establishment of liver
fibrosis, the basement membrane components
collagen type IV, entactin and
laminin increase and form a basement
membrane-like structure within the
space of Disse. The number of endothelial
fenestrae of the sinusoids
decreases. These changes of the sinusoids
are called 'capillarization'
because the altered structure of the
sinusoids resembles that of
capillaries. At the cellular level, origin
of liver fibrogenesis is
initiated by the damage of hepatocytes,
resulting in the recruitment of
inflammatory cells and platelets, and
activation of Kupffer cells, with
subsequent release of cytokines and growth
factors. The hepatic stellate
cells seem to be the primary target cells
for these inflammatory stimuli,
because during fibrogenesis, they undergo an
activation process to a
myofibroblast-like cell, which represents
the major matrix-producing cell.
Based on this pathophysiological mechanism,
therapeutic methods are
developed to inhibit matrix synthesis or
stimulate matrix degradation. A
number of substances are currently being
tested that either neutralize
fibrogenic stimuli and prevent the
activation of hepatic stellate cells,
or directly modulate the matrix metabolism.
However, until now, the
elimination of the hepatotoxins has been the
sole therapeutic concept
available for the treatment of liver
fibrogenesis in humans. [References:
75]
2195.
Sanyal A.
Title
Nonalcoholic steatohepatitis. [Review] [79
refs]
Source
Indian Journal of Gastroenterology. 20 Suppl 1:C64-70, 2001 Mar.
2196.
Senyuz OF. Yesildag E.
Emir H. Tekant G. Bozkurt P.
Sarimurat N.
Soylet Y.
Title
Diagnostic laparoscopy in prolonged
jaundice.
Source
Journal of Pediatric Surgery. 36(3):463-5, 2001 Mar.
Abstract
BACKGROUND: The early diagnosis of surgical
jaundice in a neonate is an
important step for the surgical success in
extrahepatic biliary atresia.
Diagnostic laparoscopy, as in many areas in
surgery, is included in the
conventional diagnostic methods of
extrahepatic biliary atresia. METHODS:
Since 1992, 24 infants with prolonged
jaundice, in whom extrahepatic
biliary atresia and neonatal hepatitis could
not be differentiated with
conventional diagnostic interventions, have
been evaluated
laparoscopically. RESULTS: A coarse,
irregular, greenish-brown liver with
some degree of fine angiomatous development
and an atretic gallbladder are
the findings of laparoscopic evaluation in
an infant with extrahepatic
biliary atresia. However, in neonatal
hepatitis, the liver is smooth,
sharp-edged, and chocolate brown in color,
and simultaneously performed
cholangiography should show the passage of
the contrast material both into
the proximal biliary tracts and the
intestinal system. In this series, 10
of 24 cases were proved to be neonatal
hepatitis diagnosed by laparoscopy,
so unnecessary laparotomy was avoided in 42%
of the cases. CONCLUSION:
When the diagnostic laparoscopy, in which
the liver and the gallbladder
are directly visualized, is combined with
the cholangiographic
examination, the most accurate and earlier
diagnosis in an infant with
prolonged jaundice can be achieved, and the
important period of time for
the surgical success in extrahepatic biliary
atresia will be minimally
wasted.
2197.
Yoon SN. Yoo BM.
Hwang KH.
Title
Hepatobiliary scintigraphy showing acute
complete common bile duct
obstruction in a patient with acute
hepatitis.
Source
Clinical Nuclear Medicine. 26(2):151-2, 2001 Feb.
2198.
Zen Y. Katayanagi K. Tsuneyama K. Harada
K. Araki I. Nakanuma Y.
Title
Hepatocellular carcinoma arising in
non-alcoholic steatohepatitis.
Source
Pathology International. 51(2):127-31, 2001 Feb.
Abstract
The incidence and significance of
hepatocellular carcinoma (HCC) in
non-alcoholic steatohepatitis (NASH) has not
been previously evaluated in
detail. We recently experienced a case of
NASH with multicentric HCC in a
female patient. At the age of 58 years, the
patient was diagnosed with
non-insulin-dependent diabetes mellitus,
treated by insulin therapy. The
patient did not drink alcohol. She was
negative for all serological
markers of hepatitis B and C virus
infection. Because of liver
dysfunction, a needle biopsy was performed
at the age of 62 years, and
pathological findings, such as fatty change,
Mallory's body, nuclear
glycogen and pericellular fibrosis,
suggested a diagnosis of NASH.
Subsequently, four nodules were detected in
the liver by imaging. Liver
biopsies were performed from each nodule.
One nodule was pathologically
diagnosed as a pseudolymphoma, while three
other nodules were moderately
differentiated HCC (10 years after the
diagnosis of non-alcoholic
steatohepatitis), well-differentiated HCC
(11 years later) and dysplastic
nodule (11 years later), suggesting
multicentric occurrence of HCC. This
case suggests that HCC could be a late
complication of NASH.
2735. Abass F.
Thomas RD. Rajkumar A. Gupta N.
Puliyel JM. Controlling perinatally acquired hepatitis B. Indian Journal
of Pediatrics. 68(4):365, 2001 Apr.
2736. Ahmed A.
Samuels SL. Keeffe EB. Cheung RC. Delayed fatal hemorrhage from
pseudoaneurysm of the hepatic artery after percutaneous liver biopsy. American
Journal of Gastroenterology.
96(1):233-7, 2001 Jan.
2737. Alper J. Searching for medicine's sweet spot.
Science. 291(5512):2338-43, 2001 Mar
23.
2738. Anonymous. From the Centers for Disease
Control and Prevention. Impact of the 1999 AAP/USPHS Joint Statement on
Thimerosal in Vaccines on Infant Hepatitis B Vaccination Practices. American
Academy of Pediatrics/U.S. Public Health Service. JAMA. 285(12):1568-70,
2001 Mar 28.
2739. Anonymous. From the Centers for Disease
Control and Prevention. Recommended childhood immunization schedule--United
States, 2001. JAMA. 285(7):875-6, 2001 Feb 21.
2740. Anonymous. Impact of the 1999 AAP/USPHS joint
statement on thimerosal in vaccines on infant hepatitis B vaccination
practices. MMWR - Morbidity & Mortality Weekly Report. 50(6):94-7, 2001 Feb 16.
2741. Anonymous. Recommended childhood immunization
schedule--United States, 2001. MMWR - Morbidity & Mortality Weekly
Report. 50(1):7-10, 19, 2001 Jan 12.
2742. Ascherio A.
Zhang SM. Hernan MA. Olek MJ.
Coplan PM. Brodovicz K. Walker AM.
Hepatitis B vaccination and the risk of multiple sclerosis. [see
comments]. New England Journal of Medicine.
344(5):327-32, 2001 Feb 1.
2743. Authier FJ.
Cherin P. Creange A. Bonnotte B.
Ferrer X. Abdelmoumni A. Ranoux D.
Pelletier J. Figarella-Branger
D. Granel B. Maisonobe T. Coquet
M. Degos JD. Gherardi RK. Central nervous system disease in patients with
macrophagic myofasciitis. Brain. 124(Pt
5):974-83, 2001 May.
2744. Bah E.
Parkin DM. Hall AJ. Jack AD.
Whittle H. Cancer in the Gambia: 1988-97. British Journal of Cancer.
84(9):1207-14, 2001 May 4.
2745. Bates I.
Bedu-Addo G. Jarrett RF. Schulz T.
Wallace S. Armstrong A. Sheldon J.
Rutherford T. B-lymphotropic
viruses in a novel tropical splenic lymphoma. British Journal of Haematology. 112(1):161-6, 2001 Jan.
2746. Berger A.
Preiser W. Doerr HW. The role of
viral load determination for the management of human immunodeficiency virus,
hepatitis B virus and hepatitis C virus infection. [Review] [39 refs] Journal of Clinical Virology. 20(1-2):23-30, 2001 Jan.
2747. Brecher LS.
Cymet TC. A practical approach to fibromyalgia. [Review] [45 refs] Journal of the American Osteopathic
Association. 101(4 Suppl Pt 2):S12-7,
2001 Apr.
2748. Bryan JP.
McCardle P. South-Paul JE. Fogarty JP.
Legters LJ. Perine PL.
Randomized controlled trial of concurrent hepatitis A and B vaccination.
Military Medicine. 166(2):95-101, 2001
Feb.
2749. Caldwell SH.
Hespenheide EE. von Borstel RW.
Myositis, microvesicular hepatitis, and progression to cirrhosis from
troglitazone added to simvastatin. Digestive Diseases & Sciences. 46(2):376-8, 2001 Feb.
2750. Calleja JL.
Albillos A. Rossi I. Moreno R.
Domper F. Martinez JL. Escartin P. Time course of serum hepatitis C
virus-RNA during chronic hepatitis C treatment accurately predicts the type of
response. Alimentary Pharmacology & Therapeutics. 15(2):241-9, 2001 Feb.
2751. Chan CH.
Hadlock KG. Foung SK. Levy S. V(H)1-69 gene is preferentially used
by hepatitis C virus-associated B cell lymphomas and by normal B cells
responding to the E2 viral antigen. Blood.
97(4):1023-6, 2001 Feb 15.
2752. Chodick G.
Lerman Y. Peled T. Aloni H.
Ashkenazi S. Cost-benefit analysis of active vaccination campaigns
against hepatitis A among daycare centre personnel in Israel. Pharmacoeconomics. 19(3):281-91, 2001.
2753. Christenson
JC. Fischer PR.
Hale DC. Derrick
D. Pediatric travel consultation in an integrated clinic. Journal of Travel Medicine. 8(1):1-5, 2001 Jan-Feb.
2754. Colombo M. Screening for cancer in viral
hepatitis. [Review] [60 refs] Clinics in Liver Disease. 5(1):109-22, 2001 Feb.
2755. Daar ES.
Lynn H. Donfield S. Gomperts E.
Hilgartner MW. Hoots WK. Chernoff D.
Arkin S. Wong WY. Winkler CA.
The Hemophilia Growth and Development Study. Relation between HIV-1 and hepatitis C viral load in patients
with hemophilia. Journal of Acquired
Immune Deficiency Syndromes.
26(5):466-72, 2001 Apr 15.
2756. Davidovici B. Karakis I. Bourboulia
D. Ariad S. Zong J. Benharroch
D. Dupin N. Weiss R. Hayward G. Sarov B.
Boshoff C. Seroepidemiology and molecular epidemiology of Kaposi's
sarcoma-associated herpesvirus among Jewish population groups in Israel. Journal of the National Cancer
Institute. 93(3):194-202, 2001 Feb 7.
2757. Doshi AV.
Desai D. Bhaduri A. Udwadia ZF. Lymphocytic interstitial
pneumonitis associated with autoimmune hepatitis. Indian Journal of Gastroenterology. 20(2):76-7, 2001 Mar-Apr.
2758. Dudas J.
Kovalszky I. Gallai M. Nagy JO.
Schaff Z. Knittel T. Mehde M.
Neubauer K. Szalay F. Ramadori G. Expression of decorin,
transforming growth factor-beta 1, tissue inhibitor metalloproteinase 1 and 2, and
type IV collagenases in chronic hepatitis.
American Journal of Clinical Pathology.
115(5):725-35, 2001 May.
2759. Ericsson
CD. Travel medicine: key to improved adult vaccination against Hepatitis
A and B. [letter; comment]. Journal of
Travel Medicine. 8 Suppl 1:S1-2, 2001
Jan.
2760. Faustini A.
Franco E. Sangalli M. Spadea T.
Calabrese RM. Cauletti M. Perucci CA. Persistence of anti-HBs 5 years
after the introduction of routine infant and adolescent vaccination in Italy.
Vaccine. 19(20-22):2812-8, 2001 Apr 6.
2761. Fisher MA.
Eklund SA. James SA. Lin X. Adverse events associated with
hepatitis B vaccine in U.S. children less than six years of age, 1993 and 1994.
Annals of Epidemiology. 11(1):13-21,
2001 Jan.
2762. Fracanzani AL. Conte D. Fraquelli
M. Taioli E. Mattioli M. Losco A. Fargion S. Increased cancer risk in a cohort
of 230 patients with hereditary hemochromatosis in comparison to matched
control patients with non-iron-related chronic liver disease. Hepatology. 33(3):647-51, 2001 Mar.
2763. Gilbert P.
Self S. Rao M. Naficy A.
Clemens J. Sieve analysis: methods for assessing from vaccine trial data
how vaccine efficacy varies with genotypic and phenotypic pathogen variation.
[Review] [65 refs] Journal of Clinical Epidemiology. 54(1):68-85, 2001 Jan.
2764. Gout O. Vaccinations and multiple sclerosis.
New England Journal of Medicine.
344(23):1794; discussion 1795, 2001 Jun 7.
2765. Harcourt C.
van Beek I. Heslop J. McMahon M.
Donovan B. The health and welfare needs of female and transgender street
sex workers in New South Wales. Australian & New Zealand Journal of Public
Health. 25(1):84-9, 2001.
2766. Herold C.
Heinz R. Radespiel-Troger
M. Schneider HT. Schuppan D.
Hahn EG. Quantitative testing of liver function in patients with
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2805. Whitehead MW. Hainsworth I. Kingham JG.
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