Individuals
with advanced liver fibrosis typically respond less well to interferon-based therapy,
and treatment for those with decompensated cirrhosis is considered contraindicated,
due to the risk of serious side effects. Yet this group of patients has the greatest
need for effective therapy in order to avoid liver
transplantation or death.
In
the first study, published in the December 2006 Journal of Viral Hepatitis,
French researchers compared sustained virological
response (SVR) rates in 203 chronic hepatitis C patients with severe fibrosis.
Participants were randomly assigned to receive PegIntron at either the standard
dose of 1.5 mcg/kg/week or a half dose of 0.75 mcg/kg/week for 48 weeks; all patients
also received 800 mg/day ribavirin.
Results
45 out of 101 patients (44.5%) achieved SVR with the standard dose of PegIntron,
compared with 38 out of 102 patients (37.2%) treated with the lower dose (P =
non-significant).
In patients with HCV genotypes 1, 4, or 5, SVR was observed in 25.0% of patients
who received the standard dose and 16.9% of those who received the lower dose
(P = non-significant).
- In patients with these genotypes and low baseline
HCV viremia, the SVR rates were again similar (27.3% vs 25.8%; P = non-significant).
- In the high-viremia subgroup, 24.0% and 9.1% of patients, respectively,
achieved SVR.
In patients with genotypes 2 or 3, SVR rates were higher, but also similar in
the standard and low-dose groups (73.2% vs 73.0%; P = non-significant).
"[P]atients
with genotypes 2 and 3 and severe fibrosis can be treated with low dose pegylated
interferon and ribavirin," the authors concluded, adding that "more
studies are needed for patients with genotype 2 or 3 to define the optimal duration
(24 or 48 weeks) in patients with severe fibrosis."
Further,
they wrote, "this study suggests that patients with genotypes 1, 4, and 5
and high viremia could receive a standard dose of pegylated interferon associated
with ribavirin for 48 weeks." However, they noted that "side effects
limit the efficacy of the treatment with standard dose pegylated interferon in
patients with genotypes 1, 4 and 5 and low viremia."
Study
2
In
the second study, described in the October 20, 2006 electronic edition of the
Journal of Hepatology, Italian researchers assessed long-term outcomes
in patients with decompensated HCV-related cirrhosis treated with antiviral therapy.
Of 129 eligible participants, 66 patients received PegIntron plus ribavirin for
24 weeks, while 63 control subjects remained untreated (currently the standard
of care for individuals with decompensated liver disease).
Results
27 patients tolerated therapy, while 26 had their doses reduced due to toxicity,
and 13 discontinued due to intolerance.
End-of-treatment response rates were 82.6% for patients with HCV genotypes 2 or
3, and 30.2% for those with genotypes 1 or 4.
Sustained virological response (SVR) rates were 43.5% for genotype 2 or 3 patients,
and 7.0% for genotype 1 or 4 patients.
During treatment, odds ratios for severe infections or deaths due to infection
were 2.95 (95% CI 0.93-9.3) and 1.97 (95% CI 0.40-9.51) in treated patients compared
with untreated control subjects.
During a follow-up period of 30 months off-therapy, decompensation events occurred
in 52 control subjects, 33 non-responders to treatment, and 3 patients who achieved
SVR.
Odds ratios for ascites, encephalopathy, and esophageal bleeding in treated patients
decreased significantly in comparison with untreated control subjects.
The annualized incidence of death was 2.34 per 1000 person-years for untreated
controls, compared with 1.91 for non-responders and 0 for sustained responders.
Survival
curves showed early separation of sustained responders from both non-responders
and untreated controls at approximately 6 months.
In
conclusion, the authors wrote, "In decompensated cirrhotics, HCV clearance
by therapy is life-saving and reduces disease progression."
12/08/06
References
A
Abergel, C Hezode, V Leroy, and others. Peginterferon alpha-2b plus ribavirin
for treatment of chronic hepatitis C with severe fibrosis: a multicentre randomized
controlled trial comparing two doses of peginterferon alpha-2b. Journal of
Viral Hepatitis 13(12): 811-820. December 2006.
A
Iacobellis, M Siciliano, F Perri, and others. Peginterferon alfa-2b and ribavirin
in patients with hepatitis C virus and decompensated cirrhosis: a controlled study.
Journal of Hepatology. October 20, 2006 [Epub ahead of print].
45 out of 101 patients (44.5%) achieved SVR with the standard dose of PegIntron,
compared with 38 out of 102 patients (37.2%) treated with the lower dose (P =
non-significant). 
