Interferon for interferon nonresponding and relapsing patients with chronic hepatitis C

Abstract

Background: Interferon monotherapy leads to sustained virologic clearance in a minority of patients with chronic hepatitis C. Studies have yielded conflicting results regarding retreatment with interferon in nonresponders and relapsers.

Objectives: To assess the beneficial and harmful effects of retreatment with interferon in chronic hepatitis C nonresponders and relapsers to previous interferon treatment.

Search strategy: Trials were identified through electronic databases, manual searches, authors, and pharmaceutical companies (August 2001).

Selection criteria: Randomised trials comparing interferon versus control or different interferon regimens in chronic hepatitis C patients being nonresponders and relapsers to previous interferon were included.

Data collection and analysis: The primary outcome was failure to achieve a sustained virologic response defined as positive serum hepatitis C virus RNA at least six months following treatment. Secondary outcomes included liver-related morbidity, mortality, biochemical responses, adverse events, and histology.

Main results: Ten randomised trials involving 686 nonresponders and eight trials involving 484 relapsers were included; their methodological quality was poor. In nonresponders, interferon reduced the risk of not achieving an end of treatment biochemical response compared with no treatment (relative risk [RR] 0.77, 95% confidence interval [CI] 0.66 to 0.91); however, virologic responses were not reported. In a post hoc subgroup analysis, doses greater than 3 million units (MU) three times weekly offered no advantage compared with 3 MU three times weekly for biochemical sustained response. Failure to obtain a virologic sustained response was less likely with 48 than 24 weeks of therapy (RR 0.87, 95% CI 0.79 to 0.96). Adverse events did not differ significantly regardless of treatment dose or duration. In relapsers, none of the trials compared interferon with no treatment. In a post hoc analysis, doses greater than 3 MU three times weekly were no more effective in achieving a virologic sustained response than 3 MU three times weekly. Compared with 24 weeks, treatment durations of 48 weeks were less likely to fail to achieve a virologic sustained response (RR 0.69, 95% CI Random 0.51 to 0.95), but associated with more frequent dosage reduction (RR 9.07, 95% CI 1.20 to 68.63). No data regarding clinical outcomes or histology was available in either patient group.

Reviewer's conclusions: Retreatment with interferon leads to sustained virologic clearance in a minority of chronic hepatitis C patients with nonresponse or relapse following interferon monotherapy. Treatment durations of 48 weeks are superior to 24 weeks, but doses greater than 3 MU three times weekly are no more effective. No data exists regarding the effect on clinical outcomes.