Management of interferon relapsers

Relapse in patients who have evidenced an initial response to a course of interferon monotherapy for chronic hepatitis C virus (HCV) infection has been a major frustration. At least 70% of responders will relapse after a 6-month course of treatment and more than 50% will relapse after a 12-month course of treatment, usually within the first 3 to 6 months after treatment discontinuation. At most, half of patients relapsing after an initial 6-month course will have a sustained response to a second, 12-month course of interferon monotherapy. A more promising second-line regimen is the combination of interferon plus ribavirin. A recent multicenter international trial has shown that this regimen results in a sustained virologic response rate of nearly 50%, fully 10-fold higher than the sustained response rate observed with a second 6-month course of interferon alone (49% vs 5%, respectively). In patients with non-1 genotype and viral levels no greater than 2 million copies/mL, the likelihood of sustained response to the second course of combination therapy was 100%. Biochemical and virologic responses (normalization of liver enzymes and disappearance of HCV RNA from the serum) were frequently accompanied by histologic improvement. HCV-RNA levels < or = 2 million copies/mL and non-1 viral genotype predicted treatment response, whereas age, gender, body weight, source of infection, type of interferon used for the first round of treatment, and elapsed time since first treatment had no effect. Based on these data, combination therapy with interferon and ribavirin is now considered the treatment of choice for relapsers. It is not clear whether 12 months of combination therapy might have produced even better rates of viral eradication in relapsed patients.