HEPATOLOGY WATCH®
Timely
Information for Practicing Physicians
December
1999
highlights from the 50th annual meeting
of
the American association for the study of liver
diseases
November 5-9, 1999
HEPATOLOGY, VOLUME 30, 1999
Liver
Failure
Etiology and outcome of acute liver failure (ALF). George Ostapowicz
and colleagues in the ALF study group reported preliminary findings on 110
patients with ALF followed prospectively in the United States. They found acetaminophen poisoning to be the
most common cause of ALF (34% of cases), of which 22 (59%) were accidental. Other diagnostic categories were
idiosyncratic drug reactions (20%), hepatitis A and B (11%) and indeterminate
(19%). Outcomes were as follows: 30% of
patients underwent liver transplantation; 33% of patients died without
transplantation; and 36% of patients were spontaneous survivors. The overall survival rate was 61%. The spontaneous survivors tended to be
younger patients with acetaminophen poisoning and lower serum bilirubin
levels. In a second abstract,
Ostapowicz et al. reported that spontaneous survival was associated with an
increase between days 1 and 3 in the serum alpha-fetoprotein level, which is
known to be associated with hepatic regeneration. (Abstracts 243 and 17)
Portal
Hypertension
Nadolol
(NAD) and isosorbide mononitrate (IMN) for prophylaxis of variceal bleeding. Two studies investigating the role of NAD
and IMN therapy for primary and secondary prophylaxis of variceal bleeding were
reported. Carlo Merkel et al. reported
in a study of 146 cirrhotic patients with esophageal varices that long-term
prophylaxis (up to 7 years) with NAD + IMN more effectively prevented the first
episode of variceal bleeding than NAD therapy alone (log-rank p=0.05). The cumulative risk of bleeding was 29% and
12%, respectively. Josep Minyana and
colleagues compared NAD + IMN therapy (n=69) to endoscopic ligation (n=70) for the prevention of recurrent
variceal bleeding. The NAD + IMN
patients had fewer therapeutic failures (16% vs. 26%) and a higher 1-year
probability of remaining free of variceal rebleeding (78% vs 60%, p=0.04). These results indicate that NAD + IMN is
effective therapy for both primary and secondary prophylaxis of variceal
bleeding. (Abstracts 217 and 215)
Primary
Biliary Cirrhosis (PBC)
Etiology. Three abstracts addressed the issue of the
etiology of PBC. These studies found
evidence of a transmissible factor from PBC lymph nodes (A. Keogh et al.), that
a variation in the incidence of PBC exists between adjacent health districts in
the U.K. (J. Metcalf et al.), and that epidemiologic data suggest the
possibility of an infectious etiology (A. Parikh-Patel). These results indicate that there may be
environmental etiologic factors for PBC.
(Abstracts 1236, 1239, 1242)
Nonalcoholic Steatohepatitis (NASH)
Prognostic factors. Angulo and
colleagues studied 144 NASH patients and identified by multivariate analysis
that age (p< 0.001), obesity
(p=0.002), diabetes mellitus (p=0.009), and AST/ALT ratio >1 (p=0.03) were
independent predictors of severe hepatic fibrosis. This group of patients may benefit from liver biopsy and
investigational therapies. (Abstract
981)
Hepatitis
B Virus (HBV) Infection
Lamivudine
(LAM) therapy. Robert Perrillo et
al. reported the results of a multicenter trial of LAM therapy for HBV patients
with end-stage liver disease who were orthotopic liver transplant (OLT) candidates
(n=77). Twenty-seven patients on extended LAM therapy (median duration of 762
days, range 5-1,128) did not undergo OLT and are the subject of this
report. LAM therapy was well tolerated
and associated with biochemical and clinical improvement in this subset of
patients. LAM treatment may obviate or
delay the need for OLT. Peter Angus et
al. studied the use of post-transplant LAM combined with low-dose intramuscular
hepatitis B immune globulin (HBIG) and found that this regimen effectively prevented
recurrence of HBV infection in 32 patients followed for a mean of 13 months
(range 1-41). This combination is
likely to be more cost-effective than the intravenous high-dose HBIG regimens
in current use. (Abstracts 561 and 563)
Hepatitis
C Virus (HCV)
Review of therapeutic approaches. Mitchell Shiffman
et al. reviewed the recent Schering international and U.S. registration trials
of interferon (IFN) +/- ribavirin (RBV) and observed that an improvement in
hepatic histology was associated with a decline in serum HCV RNA levels, even
in patients with a virologic nonresponse.
The improved histology was noted in patients with a 1 log or greater
decrease in HCV RNA levels, which occurred in 25-33% of nonresponders. Another review of 4 trials (Gary Davis et
al.) showed that patients remaining HCV RNA (-) x 6 months after completion of
therapy rarely relapse and that late relapse is only slightly less common when
RBV is added to IFN. A trial by Vito
Dimarco et al. of IFN + RBV treatment for relapsing HCV patients (n=50) with
high viremia or genotype 1b infection demonstrated that 12 months of therapy
results in a higher sustained response rate than 6 months of therapy
(p=0.01). Once-weekly pegylated IFN
(PEG-IFN) proved to be safe and to result in higher response rates than IFN at
48 weeks (43% vs 13%) in a study of 271 INF-naļve chronic HCV patients with
compensated cirrhosis (E. Heathcote et al).
Finally, experiments in chimpanzees (Krawczynaski et al.) indicate that
multiple infusions of anti-HCV immunoglobin has antiviral effects clinically
and may prevent acute hepatitis C.
Maternal risk factors. . A multivariate analysis identifying risk
factors for maternal HCV transmission from a cohort study of 323 infants born to
HCV-infected mothers was presented.
Risk factors were materal HCV RNA positivity at time of delivery,
maternal HCV RNA titer greater than one million eq/mL, prolonged membrane
rupture, use of internal fetal monitoring devices and meconium stained amniotic
fluid. Finally, RT-PCR analysis was
found to identify HCV RNA (+) donors (0.046%) from a population of anti-HCV
ELISA (-) individuals in a study of 48,000 normal plasma donors (Richard Smith
et al.). (Abstracts 567, 569, 621,
1354, 1359, 570, 1040)
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