Long-term responders without eradication of hepatitis C virus after interferon therapy: characterization of clinical profiles and incidence of hepatocellular carcinoma.

Abstract

The aim of this study was to determine the characteristics of patients with chronic hepatitis C showing long-term normalization of alanine aminotransferase (ALT) without eradication of HCV RNA, as well as to investigate the incidence of hepatocellular carcinoma (HCC) in such patients. Four hundred and nineteen patients with histologically-proven chronic hepatitis C who had received interferon (IFN) therapy were studied. Complete response (CR) was defined as persistent normalization of ALT levels with eradication of serum HCV RNA (n= 126). Long-term biochemical response with positive HCV RNA (HCV-positive BR) was defined as a normal ALT level at 6 months after IFN therapy with further persistent normalization of ALT levels for 2 or more years without eradication of serum HCV RNA (n=49). All other patterns were classified as non-response (NR, n=244). Mean follow-up periods of CR, HCV-positive BR and NR groups were 4.9, 5.2 and 4.9 years, respectively. The HCV-positive BR group had significantly higher serum HCV RNA levels and a higher rate of HCV serological group 1 classification than the CR group. The other characteristics of the HCV-positive BR group were lower histologic activity, lower ALT levels, and a higher rate of females when compared with both the CR and NR groups. Histologic staging in the HCV-positive BR group was significantly lower than that in the NR group. Cumulative incidences of HCC estimated by the Kaplan-Meier method in both the CR and HCV-positive BR groups were significantly lower than those in the NR group (log-rank test, CR vs NR p<0.001, HCV-positive BR vs NR p=0.026). The patients with HCV-positive BR were virologically different from those with CR, and had lower ALT levels and histologic activity when compared to those with CR and NR.