HEPATOLOGY WATCH®
Timely
Information for Practicing Physicians
NOVEMBER
2001
TREATMENT OF Chronic Hepatitis
Peginterferon plus ribavirin for
chronic hepatitis C virus (HCV) infection. Michael Manns and colleagues conducted a 3-arm study in which
1,530 previously untreated patients with chronic HCV infection were randomized
to receive 48 weeks of: 1) interferon alfa-2b (3 MU 3 times weekly) plus
ribavirin (1,000-1,200 mg/day); 2) peginterferon alfa-2b 1.5 ug/kg weekly plus
ribavirin 800 mg/day; or 3) peginterferon 1.5 ug/kg weekly for 4 weeks then 0.5
ug/kg weekly plus ribavirin 1,000-1,200 mg/day. A greater sustained virological response (SVR) rate was achieved
in the high-dose peginterferon group (54%) than in either the low-dose peginterferon
group (47%) or the interferon group (47%) (p=0.01). Among patients with HCV genotype 1 infection, the SVR rates were
42%, 34%, and 33% in the high- and low-dose peginterferon and the interferon
groups, respectively. Among patients with genotype 2 and 3 infections, the SVR
rates were about 80% for all treatment groups.
These data indicate that the combination of high-dose peginterferon plus
ribavirin is the most effective initial therapy for chronic HCV patients and
that the increased benefit is mostly achieved in patients with HCV genotype 1
infection. (Manns MP, et al. Lancet 2001;358:958-965)
Interferon alpha-2b and lamivudine
for chronic hepatitis B virus (HBV) infection. Giuseppe Barbaro and colleagues randomized 151 patients with
chronic HBV infection to receive either interferon alpha-2b (9 MU 3 times
weekly) plus lamivudine 100 mg daily for 24 weeks or lamivudine monotherapy for
52 weeks. Sustained HBeAg
seroconversion was observed in 33% of the combination therapy patients compared
to 15% of the monotherapy patients (p=0.014), and histological improvement was
found in 46% of the combination therapy patients versus 27% of the monotherapy
patients (p=0.021). The results of this
study indicate that 6 months of combination therapy (interferon alpha-2b plus
lamivudine) increased the rate of sustained HBeAg seroconversion and improved
histological findings compared to 1 year of lamivudine monotherapy. (Barbaro G, et al. J Hepatol 2001;35:406-411)
TREATMENT
OF Primary Sclerosing Cholangitis (PSC)
High-dose ursodeoxycholic acid
(UDCA). Stephen Mitchell
and colleagues report the findings of a 2-year double-blind study in which 26
patients with PSC were randomized to high-dose UDCA (20 mg/kg daily) or
placebo. Previous studies had shown
that standard doses of UDCA (8-15 mg/kg) were ineffective in patients with
PSC. High-dose UDCA did not influence
symptoms, but was associated with an improvement in liver biochemistry and a
reduction in progression of cholangiographic appearances (p=0.15) and hepatic
fibrosis (p=0.05). No side effects were
reported. Larger studies are warranted
to determine the clinical benefit of high-dose UDCA therapy in PSC, which
appears quite promising. (Mitchell SA,
et al. Gastroenterology 2001;121:900-907)
Autoimmune Hepatitis
Bile duct injury. Albert Czaja and Herschel Carpenter reviewed
liver biopsy specimens from 84 patients with autoimmune hepatitis. Twenty patients (24%) had biliary changes (6
with destructive cholangitis, 10 with nondestructive cholangitis, and 4 with
ductopenia). Diagnostic scores for
autoimmune hepatitis were lower in patients with duct changes (p=0.03). However, patients with duct changes had
similar laboratory findings and responded to therapy as well as patients
without duct changes. These data show
that biliary changes occur in autoimmune hepatitis and that they are not
associated with distinctive clinical features or an altered response to
treatment. (Caza AJ and Carpenter HA. Hepatology 2001;34:659-665)
treatment
of Nonalcoholic Steatohepatitis (NASH)
Betaine therapy. Betaine is a naturally occurring metabolite
of choline that has been shown to raise S-adenosylmethionine levels that may in
turn decrease hepatic steatosis. Manal Abdelmalek and associates treated 10
NASH patients with oral betaine (Cystadane) 10 mg bid (7 patients completed 12
months of treatment) and found significant improvement in serum biochemistry
findings. In addition, a marked
improvement in the degree of steatosis, necroinflammatory grade, and stage of
fibrosis was noted at 1 year of treatment with betaine. Transient gastrointestinal adverse events
occurred in 4 patients. These
preliminary findings indicate that betaine is well tolerated and may be
effective therapy for patients with NASH.
Further studies are warranted. (Abdelmalek MF, et al. Am J Gastroenterol
2001;96:2711-2717)
Complimentary and Alternative Medicine (CAM)
Perceptions relative to
conventional therapies. David
Eisenberg and coworkers performed a national random-household telephone survey
of 831 adults who had seen a medical doctor and had used CAM therapies in
1997. They found that patients who use
both CAM and conventional therapies value both and are more concerned about a
doctor's inability to use or understand CAM therapy than they are concerned
about their doctor's disapproval.
(Eisenberg DM, et al. Ann Intern Med 2001;135:344-351)
Hepatic evaluation
Liver biopsy. Maeve Skelly et al reviewed the histological
findings of 354 patients who underwent liver biopsy to investigate abnormal
liver function tests in the absence of diagnostic serology. Liver biopsy results directly altered the
management of 18% of patients. Six
percent of patients had a normal biopsy, while fibrosis was found in 26% of patients
and cirrhosis in 6% of patients. These
data demonstrate that abnormal liver function tests may indicate significant
liver disease and liver biopsy may yield a diagnosis for which specific
treatment is indicated. (Skelly MM, et al. J Hepatol 2001;35:195-199)
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