COMPARISON OF PEGINTERFERON ALFA-2A AND RIBAVIRIN FOR 12 OR 24 WEEKS IN PATIENTS WITH HCV GENOTYPE 2 OR 3: THE CLEO TRIAL

Background: In chronic hepatitis C (CHC) patients with genotype 2 or 3, 24 weeks treatment with peg-interferon and ribavirin induces a sustained virological response (SVR) in about 80% of the cases. Recent trials have shown that a similar response rate may be obtained with a shorter treatment period (12 or 16 weeks), especially in patients with rapid virologic response (RVR). Endpoints. Primary endpoint of the study was to assess whether 12 week treatment with peg-interferon and ribavirin is as efficacious as 24 week treatment in inducing a SVR in CHC patients with genotype 2 or 3. Secondary endpoint was the rate of relapsers among groups. Methods.We performed a multicenter, prospective, randomized trial on 180 histologically confirmed CHC patients with genotype 2 or 3 enrolled in 11 italian centers. All patients were treated with peg-interferon alpha2a (180 mcg/week) and ribavirine (800- 1200mg/day). After 4 weeks of treatment, the patients with HCV-RNA <600 UI/ml (RVR) were randomized either to 12 weeks (Group A1; n=60) or to 24 weeks (Group A2; n=60) of combination therapy in a 1:1 ratio. The patients without RVR continued standard 24 weeks combination therapy (Group B n=60). In all groups of patients HCV-RNA was checked 12 and 24 weeks after the end of therapy. Results. At the end of the study period SVR was observed in 74% of patients of Group A1, in 84% of patients of Group A2 and in 54% of patients of Group B (P<0.05 vs Groups A1 and A2). Relapsers rate at the end of the study period was 3% in Group A1, 2% in Group A2 and 6% in Group B. Logistic regression analysis showed that baseline HCV-RNA< 1 million/UI/ml (OR: 3.5; P<0.001), a baseline histological inflammation score <7 (OR:2.5; P<0.001), a fibrosis score <2 (OR: 3.3; P<0.001) and a RVR <4 week (OR: 3.5; P<0.001) were the strongest covariates predictive of SVR. Conclusions. In CHC patients with genotype 2 or 3, 12 week combination therapy is as efficacious as 24 week therapy. A RVR is an independent covariate predictive of SVR along with low baseline HCV levels and a low baseline histological inflammation and fibrosis score without significant differences in the rate of relapsers.