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HCV Treatment — How Short Can We Go?

For genotypes 2 and 3, 24-week treatment is more effective than 16-week treatment.

Patients infected with hepatitis C virus (HCV) genotypes 2 and 3 tend to be very responsive to combination therapy with pegylated interferon and ribavirin. Consequently, current guidelines recommend 24 weeks of treatment for such patients, in contrast to the 48 weeks recommended for patients infected with genotype 1. Could treatment for HCV genotypes 2 and 3 be shortened even further — to 16 weeks?

In a manufacturer-supported, randomized trial involving 1469 patients infected with HCV genotypes 2 or 3, investigators compared 16- and 24-week courses of treatment with peginterferon alfa-2a (180 µg once weekly) and ribavirin (400 mg twice daily).

A higher percentage of patients completed the full course of treatment in the 16-week arm than in the 24-week arm (94% vs. 87%). However, in an intention-to-treat analysis, the sustained virologic response rate 24 weeks after completion of treatment was significantly lower with 16 weeks of therapy than with 24 weeks (62% vs. 70%); similar results were found in a per-protocol analysis (65% vs. 76%). The following factors were predictive of sustained virologic response: 24 weeks of therapy, infection with HCV genotype 2, pretreatment serum HCV RNA level <400,000 IU/mL, age 45, weight 80 kg, elevated alanine aminotransaminase levels, and absence of bridging fibrosis or cirrhosis. Patients with rapid virologic responses (at 4 weeks) also had higher rates of sustained virologic response. The incidence of adverse events was similar between groups; 4% of the 16-week group and 5% of the 24-week group were withdrawn from treatment because of adverse events or laboratory abnormalities.

Comment: Although this study highlighted the efficacy of longer treatment, the toxicity of the current regimens remains a concern, even with shorter courses. In the future, HCV therapy might involve individualizing the duration of treatment based on the many factors known to influence response.

— Richard T. Ellison III, MD

Published in Journal Watch Infectious Diseases July 11, 2007

Citation(s):

Shiffman ML et al. Peginterferon alfa-2a and ribavirin for 16 or 24 weeks in HCV genotype 2 or 3. N Engl J Med 2007 Jul 12; 357:124-34.

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• Medline abstract (Free)

Liang TJ. Shortened therapy for hepatitis C virus genotype 2 or 3 — Is less more? N Engl J Med 2007 Jul 12; 357:176-8.

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• Medline abstract (Free)