Clinical characteristics of patients with chronic hepatitis C showing biochemical remission, without hepatitis C virus eradication, as a result of interferon therapy

During long-term follow-up of patients chronically infected with the hepati tis C virus (HCV) and treated with interferon (IFN), we identified some who had persistent normalization of serum alanine aminotransferase (ALT) but r emained positive for HCV RNA. The aims of this study were to clarify the ch aracteristics of these patients and to examine their clinical outcome after treatment. Nine hundred and ninety-eight patients treated with IFN were fo llowed-up biochemically and virologically, and by liver ultrasound, for 13- 95 months. A short-term biochemical sustained response, where ALT remained within the normal range for 6 months after the completion of IFN therapy, w as found in 296 patients; in 240 of these patients serum HCV RNA remained u ndetectable during long-term follow-up. The rate of HCV RNA persistence was 7.09 times greater in short-term biochemical sustained responders with a h igh viral load than in those with a low viral load (P=0.0001, odds ratio [O R]=7.09), and 3.70-fold lower in those treated with a large dose of IFN tha n in those treated with a small dose (P=0.02, OR=0.27). Thirty-three (59%) of 56 patients without HCV eradication showed continuous ALT normalization for 26-80 months after cessation of IFN therapy. Short-term biochemical sus tained responders who were older (P=0.009, OR=10.43) and who were male (P=0 .03, OR=6.98) had a significantly greater probability of maintaining a norm al ALT level, even when serum HCV RNA was positive. When the incidence of H CC was investigated during long-term follow-up in patients without HCV erad ication, it was found to be significantly lower in patients with persistent ly normal ALT levels than in those with abnormal ALT levels (P=0.03). Hence , when HCV is not eradicated as a result of IFN therapy, it may induce a lo ng-term carrier state of HCV infection with normal ALT levels in older or m ale patients, in whom the cumulative incidence of HCC is markedly decreased .