Varying incidence of cirrhosis and hepatocellular carcinoma in patients with chronic hepatitis C responding differently to interferon therapy

Abstract

To determine whether interferon (IFN) therapy can reduce incidence of the development of cirrhosis and hepatocellular carcinoma equally in patients with chronic hepatitis C virus (HCV) who responded differently to therapy, a retrospective analysis of 250 patients treated with IFN was conducted. Two hundred and fifty patients with chronic HCV who were treated with IFN were classified into 3 groups based on serum aminotransferase levels during and after therapy with IFN-alpha: long term responders (n=93), short term responders (n=70), and nonresponders (n=87). Eighty-nine untreated patients served as a control group. The follow-up period was 4 years. Liver function tests, HCV RNA levels, and alpha-fetoprotein were measured each month. Imaging diagnosis was made every 6 months with ultrasonography and yearly with dynamic computed tomography. Serum and liver HCV RNA was assayed by reverse transcriptase-polymerase chain reaction and branched DNA probe. Of the 93 long term responders, 67 (72%) remained HCV RNA negative whereas 26 (28%) were HCV RNA positive. Further histologic improvement occurred only in HCV RNA negative long term responders. During the follow-up period, the overall annual incidence of cirrhosis in the 250 patients was decreased significantly compared with the control group, whereas the overall annual incidence of hepatocellular carcinoma was not. None of the long term responders but 5 (7%) short term responders and 33 (38%) nonresponders had disease progression to cirrhosis. No HCV RNA negative long term responders but 1 (3.8%) HCV RNA positive long term responder, 1 (1.4%) short term responder, and 14 (16%) nonresponders developed hepatocellular carcinoma. Long term and short term responders had significantly lower incidence of cirrhosis whereas nonresponders had significantly higher incidence of cirrhosis and hepatocellular carcinoma than the control group. Multivariate analysis showed that staging score, the presence of high viral levels, and lack of response to therapy significantly influenced the incidence of these events. These findings suggest that patients with chronic HCV responding differently to IFN therapy had different incidence of disease progression to cirrhosis and of the development of hepatocellular carcinoma, and that nonresponders should be regarded as a group at high risk for these events.