Viral and host factors in determining response of relapsers with chronic hepatitis C to retreatment with interferon

In chronic hepatitis C the rate of relapse after an end-of-treatment response to interferon may exceed 50%. The usefulness of retreatment of relapsers with interferon in obtaining a complete sustained response and the role of clinical, virological and immunological features in determining long-term efficacy of retreatment are unclear. We aimed to assess the efficacy of interferon retreatment in obtaining a complete sustained response, to evaluate whether increasing the dose may enhance responsiveness, and to identify possible predictors of sustained response. We enrolled 42 patients with biopsy-proven chronic hepatitis C without cirrhosis who had previously responded to a six-month course of Interferon-alpha(2b) (total dose: group A, 22 patients, 234 MU; group B, 20 patients, 468 MU) and then relapsed. All, except one, were HCV-RNA negative at the end of first cycle of interferon; most (31/42, 74%) were infected by HCV Ib. Subjects were randomly allocated to receive another cycle of interferon either at the original dose (group A(1): 234 MU, 11 patients; group B-1 468 MU, 10 patient) or twice the original dose (group A(2): 468 MU, 11 patients; group B-1: 936 MU, 10 patients). At the end of the second cycle of interferon, 24 subjects (57%) had normal ALT and were HCV-RNA negative, and 16 (39%) had normal ALT, but were HCV-RNA positive. A complete sustained response was obtained in eight patients (19%), at a similar rate in all treatment groups. Complete sustained responders were different from the other patients in terms of age (35.9 +/- 10.4 vs 44.1 +/- 8.8, P = 0.027), rate of infection with non-1b HCV (6/8 vs 5/34, P = 0.0005), serum HCV-RNA (74,016 vs 321,428 median copies/ml, P = 0.037) and serum levels of 90K/MAC-2 BP (5.76 +/- 3.01 vs 10.25 +/- 5.16 unitsiml, P = 0.02), an N-glycoprotein implicated in cellular defense functions. Multivariate logistic analysis validated age and HCV genotype as independent predictors of CSR. Among noncirrhotic relapsers who received a total interferon dose greater than or equal to 234 MU in the first cycle, retreatment usually induced end-of-treatment response. A complete sustained response was obtained in only one of every five subjects. Increasing the dose of interferon above that of the first cycle did not enhance the rate of sustained response. In conclusion we might assert that young subjects infected by non-1b HCV and with low levels of HCV-RNA and of 90K/MAC-2 BP are the best candidates for retreatment.