Can Some
Genotype 1 Chronic Hepatitis C Patients Benefit from Shorter Interferon-based
Treatment?
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| SUMMARY:
Carefully selected genotype 1 chronic hepatitis C patients
who experience rapid virological response (RVR) by week
4 of treatment with pegylated interferon plus ribavirin
may be able to achieve sustained virological response
(SVR) with 24 instead of 48 weeks of therapy, according
to a meta-analysis reported in the January
2010 Journal of Hepatology. However, the
researchers cautioned, overall sustained response rates
are significantly lower with shorter treatment, and
this strategy should only be considered for individuals
with low pre-treatment HCV viral load and an undetectable
level at week 4. |
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By
Liz Highleyman
Current
standard-of-care therapy for chronic hepatitis C consists of a
combination of pegylated interferon
alpha (Pegasys or PegIntron) plus weight-adjusted ribavirin
for 48 weeks for people with hard-to-treat HCV
genotypes 1 or 4, and for 24 weeks (possibly with fixed-dose
ribavirin) for those with genotypes
2 or 3.
But interferon and ribavirin can cause difficult side effects,
leading numerous research teams to explore whether a shorter duration
of therapy might be effective for some patients.
Christophe Moreno from Université Libre de Bruxelles in
Belgium and colleagues performed a meta-analysis of previous randomized
controlled trials comparing pegylated interferon/ribavirin treatment
for the standard 48 weeks versus less than 48 weeks in patients
with HCV genotype 1 who experience rapid viral decline soon after
starting therapy.
Results
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7
studies were identified for inclusion in the analysis, including
a total of 807 genotype 1 rapid responders. |
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Sustained
virological response 24 weeks after completing therapy was
significantly less frequent with shorter treatment durations
compared with the standard 48 weeks. |
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The
mean difference in SVR rate for short duration compared with
standard duration treatment was -13.6% (P = 0.004). |
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This
difference was in part attributable to a higher relapse rate
among patients treated for a short duration (mean difference
9.9%; P < 0.001). |
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In
a sensitivity analysis restricted to studies that used only
weight-adjusted ribavirin, shorter treatment duration remained
less effective than 48 weeks. |
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However,
in subgroup of patients with low baseline viral load (<
400,000 IU/mL) and undetectable HCV RNA at week 4, there was
no significant difference in SVR rates between 24 and 48 weeks
of treatment (mean difference -3.10%). |
"In
HCV-1 patients with a rapid virological response, 24 weeks of
combination therapy with [pegylated interferon alpha] and ribavirin
should be considered only in subjects with low baseline viral
load," the study authors concluded.
However, they continued, "the optimal cut-off defining low
baseline viral load and the impact of the presence of other factors
capable of altering treatment response remain subject to debate."
Besides high baseline viral load, other factors that have been
shown to predict poorer treatment response include presence of
liver cirrhosis, insulin resistance, and HIV coinfection. Shorter
duration treatment therefore may be particularly risky for such
patients.
Department of Gastroenterology and Hepatopancreatology, Hôpital
Erasme, Université Libre de Bruxelles, Bruxelles, Belgium;
Service d'Hepatologie, Hôpital Claude Huriez, Lille, France;
Service d'Hépato-Gastroentérologie, Hôpital
de Jolimont, Haine-Saint-Paul, Belgium; National Reference Centre
for Viral Hepatitis B, C and delta, Department of Virology &
INSERM U955, Hôpital Henri Mondor, Créteil, France;
INSERM U795, Lille, France.
2/16/10
Reference
C
Moreno, P Deltenre, JM Pawlotsky, and others. Shortened treatment
duration in treatment-naive genotype 1 HCV patients with rapid
virological response: A meta-analysis. Journal of Hepatology
52(1): 25-31 (Abstract).
January 2010.
