THE TREATMENT EFFECT OF ALPHA-INTERFERON IN CHRONIC HEPATITIS-B IS INDEPENDENT OF PRETREATMENT VARIABLES - RESULTS BASED ON INDIVIDUAL PATIENT DATA FROM 10 CLINICAL CONTROLLED TRIALS

Alpha interferon induces HBeAg seroconversion in about one third of tr eated patients and has become an established treatment of chronic hepa titis B. A number of smaller studies have suggested that response to t reatment is more likely to occur in patients with higher levels of tra nsaminases, with recent (adult) onset, a history of acute hepatitis, l ow levels of HBV DNA and in heterosexual males. The aim of this Europe an co-operative study was to estimate the effect of alpha interferon m ore accurately and to evaluate the influence of host pre-treatment var iables on the effect of interferon. Individual data were collected fro m 751 patients from 10 controlled clinical trials on alpha interferon (lymphoblastoid or recombinant) treatment for chronic hepatitis B. Alp ha interferon was administered to 496 patients, while 255 were untreat ed controls. Individual patient data were analysed by survival analysi s (log rank test and Cox regression analysis), stratified by trial, wi th the disappearance of HBeAg as the major endpoint. The results showe d that the HBeAg disappearance rate with or without interferon treatme nt was higher in patients with high aminotransferase levels, with a hi story of acute hepatitis and in male heterosexual patients disregardin g HIV status. If HIV-positive patients were excluded, the effect of se xual orientation was not significant. Therapy with alpha interferon in creased the a priori HBeAg disappearance rate by a factor of 1.76; the relative treatment effect of alpha interferon was independent of the tested pretreatment host variables, but dependent on the total (intend ed) interferon dose (low dose less than or equal to 200 MU/m(2) increa sed HBeAg disappearance by a factor 1.37; medium/high dose less than o r equal to 200 MU/m(2) increased HBeAg disappearance by a factor 2.05) . In conclusion, this meta-analysis suggests that the effect of alpha interferon is less than previously assumed and independent of pretreat ment host variables tested. It confirms the higher therapeutic benefit of a total dose exceeding 200 MU/m(2) and of selection of patients ba sed on disease activity and immune reactivity. Although all patients s eem to have the same;relative benefit, the absolute benefit of alpha i nterferon treatment seems to be greatest in patients with high transam inase levels and with a history of acute hepatitis. (C) Journal of Hep atology.