FACTORS PREDICTIVE OF THE RESPONSE TO INTERFERON IN PATIENTS WITH CHRONIC HEPATITIS-C

Factors predictive of the response to interferon in patients with chronic hepatitis C remain to be identified. In this study, we investigated factors predictive of the short-term response, defined as a return to normal alanine aminotransferase activity after treatment, and the long-term response defined as normal alanine aminotransferase activity 1 year after completing treatment, in 75 patients with chronic hepatitis C virus treated with recombinant alpha interferon (either 6 MUx3/week for 3 months then 3 MUx3/week for 3 months (n=27) or 3 MUx3/week for 6 months (n=48)). At the end of treatment, 42 patients (56%) had normal alanine aminotransferase activity (''responders'') and 33 (44%) had high alanine aminotransferase activity (''non-responders''). Twenty (48%) of the 42 responders had normal alanine aminotransferase activity 1 year after treatment (''sustained responders''), while 22 (52%) had high alanine aminotransferase activity (''transient responders''). The dosage of interferon was not predictive of the short-term and the long-term response to treatment. The responders differed significantly from the non-responders in terms of age, i.v. drug abuse, aspartate aminotransferase, gammaglutamyltranspeptidase and alkaline phosphatase activities, bilirubinemia, serum bile acid concentrations, prothrombin time, platelet count, ferritinemia, hyaluronic acid levels, positivity for the antibody to 5.1.1 of the recombinant immunoblot assay band and the histological fibrosis score. The following parameters were independently correlated with the short-term response in a multivariate analysis: gammaglutamyltranspeptidase activity, serum bile acid concentrations and positivity for the antibody to 5.1.1 of the recombinant immunoblot assay band. The positive and negative predictive values of gammaglutamyltranspeptidase activity (cut off=40 IU/l) and serum bile acid concentrations (cut off=12 mu M/l) were respectively 82/70% and 75/90%. The sustained and transient responders could not be distinguished on the basis of any clinical, biological or histological factors. These findings suggest that the risk factor for exposure to hepatitis C virus and the disease stage are major determinants of the short-term response to interferon. Cholestasis and bile acids appear to play a role in resistance to interferon. None of the factors studied here was predictive of the long-term response. (C) Journal of Hepatology.