Genotype 1 HCV is harder to treat than genotypes 2 or 3. Most large randomized trials have produced sustained virological response (SVR) rates of around 50% or lower in chronic hepatitis C patients with this genotype treated for the first time with pegylated interferon plus ribavirin.

A recent Japanese trial, however, observed a higher SVR rate of 61%. The double-blind study included 200 treatment-naïve adult Japanese genotype 1b patients with detectable HCV RNA, elevated alanine aminotransferase (ALT) levels, and a liver biopsy consistent with a diagnosis of chronic hepatitis C.

Participants were randomly assigned to receive either 180 mcg/week pegylated interferon alfa-2a (Pegasys) plus 600-1000 mg daily ribavirin, or the same dose of pegylated interferon as monotherapy for 48 weeks. Baseline characteristics were similar in the two arms; 62% were men, the mean age was 51-52 years, and the mean weight was 62-63 kg.

Results

At week 48, the SVR rate in the combination therapy group was significantly higher than that observed in the monotherapy arm (odds ratio 4.55; 95% CI 2.48-8.37; P < 0.001).

This difference between the two regimens was observed regardless of baseline HCV viral load (above or below 800,000 IU/mL).

Overall, no other variables besides treatment regimen significantly and independently influenced the odds of achieving SVR.

In the monotherapy arm, a lower baseline HCV RNA level (odd ratio 0.997; 95% CI 0.995-0.999; P = 0.002) and younger age (odds ratio 0.939; 95% CI 0.900-0.979; P = 0.001) significantly increased the likelihood of achieving SVR.

Adverse events were generally mild and typical of those associated with interferon-based therapy in previous studies.

Conclusion

The authors concluded that the combination of Pegasys plus ribavirin is effective and well tolerated in treatment-naïve Japanese patients infected with HCV genotype 1b, and noted that the 61% SVR rate observed in this study "exceeds those reported previously in international trials."

The reason for this difference are not clear, but it may be influenced by the fact that this study included Japanese patients, thus presumably excluding individuals of African descent who do not respond as well to interferon-based therapy.

6/16/06

Reference
T Sakai, S Iino, T Okuno, and others. High response rates with peginterferon alfa-2a (40KD) (Pegasys) plus ribavirin (Copegus) in treatment-naive Japanese chronic hepatitis C patients: a randomized, double-blind, multicenter, Phase III trial. Abstract T1811. Digestive Disease Week 2006. May 20-25, 2006. Los Angeles, CA.