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For the 30-50% of patients with chronic hepatitis C who do not respond to alpha-interferon therapy there is no alternative treatment. Some previously untreated patients have shown a biochemical response to ribavirin, but the antiviral effects of this substance on alpha-interferon-resistant cases is largely unknown. Twelve patients with chronic hepatitis C who had not responded to a 6-12 month course of alpha-interferon were included in this study. Oral ribavirin was administered at a dose of 16 mg/kg per day for 6 or 9 months. Aminotransferase levels had not significantly changed during interferon therapy but decreased significantly during ribavirin treatment (mean alanine aminotransferase at baseline, 102 +/- 18 IU/l vs. 55 +/- 14 IU/l at 6 months; P = 0.0001). Aminotransferase levels became normal in 6 cases (50%), significantly decreased in 3 patients (25%), and did not significantly change in the remaining 3 cases (25%). All patients with normalized aminotransferase values relapsed after ribavirin was discontinued and aminotransferase activity returned to pretreatment levels. Before therapy serum hepatitis C virus RNA was detected by polymerase chain reaction in 10 cases. None of them had cleared viral RNA when tested following 3, 6 and 9 months of ribavirin therapy. Side-effects were mild and reversible. In conclusion, about half of the patients with chronic hepatitis C who are unresponsive to alpha-interferon show a clear-cut biochemical response after 6-9 months of ribavirin administration. However, ribavirin does not clear circulating hepatitis C virus RNA and relapses occur after withdrawal.(

alpha-Interferon therapy normalizes aminotransferase levels in approximately 50% of the patients with chronic hepatitis C, but post-therapy relapses are common and predictive factors of sustained response remain largely unknown. We retrospectively assessed several parameters as predictors of sustained remission after a 12-month course of lymphoblastoid alpha-interferon: the Knodell histological activity index, serum levels of procollagen type III peptide, serum HCV-RNA, anti-alpha-interferon antibodies, and anti-HCV antibodies (C-100-3), all at month 12. Thirty-seven patients were studied. Fourteen patients were non-responders (38%), 15 patients experienced a sustained response (40.5%) and eight patients responded similarly but relapsed after alpha-interferon withdrawal (21.5%). A decrease in the histological activity index above 5, normalization of procollagen type III peptide levels (< 12 ng/ml) and the absence of viremia after treatment were all significantly associated with a sustained response (p = 0.008, p = 0.007 and p = 0.037, respectively). Anti-interferon antibodies were detected in only one non-responder patient. Anti-C-100-3 antibodies became undetectable at month 12 in 5 of the 15 sustained responders. The best prediction of sustained response was obtained from the three variables independent of multivariate analysis according to the following equation: F = 0.872 + 0.067 x K (decrease of histological index) -0.052 x P (procollagen type III peptide levels at month 12) -0.28 x R (HCV-RNA at month 12; R = 2 when present and R = 1 when absent). A score higher than 0 predicted sustained remission with a 100% sensitivity and specificity in this series of patients.

Pretreatment variables that could predict the response of chronic hepatitis C to interferon alfa treatment have not been fully assessed. Eighteen baseline variables were evaluated in a series of 100 consecutive patients treated with a 12 month course of interferon alfa. For the purposes of this study, response was defined as the return to normal of aminotransferase activities before the third month of treatment. Seventy per cent of the patients responded to treatment. Six variables were associated with an increased likelihood of response assessed by univariate analysis. With stepwise multiple regression analysis assessment, however, only three variables remained independently predictive of response: low gamma glutamyltransferase (gamma GT) activities (p < 0.001), absence of obesity (p = 0.005), and absence of cirrhosis (p = 0.01). The response rate in patients with gamma GT activities < 0.66 mu kat/l (n = 55) was 78% and 60% in patients with values > 0.66 mu kat/l (n = 45) (p = 0.048). Response was attained in 75% of non-obese patients (n = 80), compared with only 50% of obese patients (n = 20) (p = 0.03). Finally, 80% of patients without cirrhosis (n = 76) responded, while among those with cirrhosis (n = 24) the response rate was only 37% (p < 0.001). All 23 patients without cirrhosis, 40 years old, and with gamma GT activities >0.66 mu kat/l responded to interferon alfa (p

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