Treatment of chronic hepatitis C in patients unresponsive to interferon. Interest of re-treatment combining interferon induction therapy and ribavirin (a multicenter pilot study)

Aim About 45% of patients with chronic hepatitis C are unresponsive to the present reference treatment combining pegelated interferon plus ribavirin; before pegylated interferon was available the non-response rate was around 60%. This open multicenter pilot study, initiated before pegylated interferon became available, was designed to evaluate, in patients unresponsive to interferon monotherapy, the rate of biological and virological response and side-effects of the ribivirin- alpha 2b interferon combination. Methods The combination protocol was ribavirin (1 to 1.2 g/d) plus alpha 2b interferon at induction doses (9 MU/d the first week; 4.5 MU/d the eleven following weeks; 3 MU/2 days the 36 following weeks). Results Among the 27 included patients, 17 (63%) were viremia-negative (PCR) after 12 weeks of treatment, 9 (33%) were complete responders (undetectable viremia and normal transaminases) at the end of treatment (48 weeks) and of follow-up (72 weeks). Patients with non-1, non-4 genotypes who derived full benefit from this therapeutic strategy (6/7 (86%) were complete responders: 4/5 with genotype 3 and 2/2 with genotype 5). Quality-of-life was impaired during treatment, especially during the first 12 weeks of high-dose interferon therapy. Conclusion While waiting for new therapeutic possibilities, these good results suggest interferon induction at the beginning of treatment remains a valid option

Antiviral effect of ribavirin in early non-responders to interferon monotherapy assessed by kinetics of hepatitis C virus RNA and hepatitis C virus core antigen

BACKGROUND/AIMS: To evaluate the efficacy of ribavirin, given in second intention in non-responders to interferon alone, by studying viral kinetics. METHODS: We conducted a trial including 203 patients with chronic hepatitis C, naïve of treatment. Patients were treated with interferon three times a week with or without ribavirin and amantadine according to response. Viral kinetics were assessed by serial measurements of HCV RNA (bDNA 3.0 and Monitor 2.0) and a new assay, trak-C, able to quantify total Hepatitis C virus (HCV) core antigen. RESULTS: A significant initial drop in HCV RNA or HCV core antigen, under interferon alone, was associated with response to therapy, -4.85+/-1.33 log for HCV RNA in sustained responders versus -1.86+/-1.53 log for others groups, P<0.001. In patients receiving ribavirin in second intention, we also observed a similar drop in HCV RNA and HCV core antigen, predictive of sustained response, -2.67+/-1.26 log for HCV RNA in sustained responders versus -0.44+/-0.49 log in non-responders, P<0.001. CONCLUSIONS: Ribavirin has probably an additional antiviral effect in interferon treated patients. Kinetics of HCV RNA and HCV core antigen under treatment are highly predictive of a sustained virological response