INTERFERON-ALPHA FOR CHRONIC HEPATITIS-C - AN ANALYSIS OF PRETREATMENT CLINICAL PREDICTORS OF RESPONSE

To identify predictors of short-term and sustained ALT normalization a fter interferon treatment in adult patients with chronic hepatitis C, we performed a metanalysis of individual patients' data, with construc tion and cross-validation of a prediction rule, in 361 patients from t wo randomized trials. In one trial, 116 subjects with transfusion-rela ted chronic hepatitis C were treated with lymphoblastoid interferon (5 MU/m2 three times a week for 2 mo, then 3 MU/m2 three times a week fo r 4 or 10 mo). In the other study, 245 patients with community-acquire d chronic hepatitis C received recombinant interferon-alpha2b, (10 MU three times a week for 2 mo, then 5 MU three times a week for 4 mo; th en random allocation of subjects with normal aminotransferase levels t o stop or continue interferon for a further 6 mo). Overall, 164 subjec ts (45%; 95% confidence interval, 40% to 50%) had short-term responses ; 61 (18%; 95% confidence interval, 14% to 22%) maintained sustained r esponses. Sixty patients (17%; 95% confidence interval, 13% to 21%) wi thdrew from treatment because of side effects or subjective intoleranc e. Logistic regression analysis showed that short-term and sustained r esponse were independently predicted by lobular structure on pretreatm ent liver biopsy (p < 0.0001) and by short disease duration, defined a s the time elapsed since transfusion in posttransfusion cases or since the first observation of abnormal aminotransferase levels in cryptoge nic disease (p < 0.01). Rules to predict short-term and sustained resp onse to interferon were derived from these items, showing a discrimina tory ability of 0.73 and 0.70. We conclude that, in patients with C he patitis, presence of cirrhosis and long disease duration predict low l ikelihood of response to interferon. Although the predictive rule base d on these items is not sufficiently accurate for decision-making in i ndividual patients, it can definitely assist when applied to groups of patients for planning or interpreting therapeutic studies. The additi on of virological features such as quantitation of viremia and hepatit is C virus genotypes may improve the ability to predict treatment outc omes.