Aims: Recently, several clinical trials analyzed if extended duration
of treatment with pegylated interferon-alfa and ribavirin over 48
weeks can improve sustained virologic response (SVR) rates in HCV
genotype 1-infected patients with slow virologic response. Because
results of these clinical trials are conflicting, we performed a metaanalysis
to determine the overall impact of extended treatment
compared to standard treatment on virologic response rates in
treatment-naive HCV genotype 1 slow responders.
Methods: Literature search was performed independently by
two observers using Pub Med, EMBASE, CENTRAL and abstracts
presented in English at international liver and gastroenterology
meetings. Randomized controlled clinical trials (RCTs; but studies
that re-analyzed data retrospectively RCTs were also allowed) were
considered if they included monoinfected treatment-naive HCV
genotype 1 patients and compared treatment with pegIFN-alfa 2a
or 2b in combination with ribavirin for 48 weeks versus extended
treatment (up to 72 weeks) in slow responders. Primary and
secondary end points were SVR rates and end-of-treatment (EOT)
and relapse rates, respectively. In the present meta-analysis, study
endpoints were summarized with a DerSimonian-Laird estimate for
binary outcome basing on a random effects model.
Results: Literature search yielded seven RTCs addressing the benefit
of extended treatment with pegylated interferon-alfa and ribavirin
in treatment-naive HCV genotype 1 slow responders. In total, 1330
slow responders were included in our meta-analysis. We show
that extended treatment duration compared to the standard of
care significantly improves SVR rates in HCV genotype 1 slow
responders (12.4% improvement of overall SVR rate, 95% CI 0.055-
0.193, P = 0.0005). In addition, we show that rates of viral relapse
were significantly reduced by extended treatment (24.1% reduction
of relapse, 95% CI −0.3332 to −0.1487, P < 0.0001), whereas no
significant impact of extended treatment on EOT response rates was
found. Though extended treatment was burdened with an enhanced
rate of premature treatment discontinuation due to interferonalfa-
and ribavirin-related side effects, the frequency of serious
adverse events was not increased.
Conclusions: Treatment extension in HCV genotype 1 slow
responders can improve SVR rates in difficult to treat patients and
should be considered in patients who need to be treated before
specific antivirals will be approved.