Histological improvement of chronic liver disease after spontaneous serum hepatitis C virus clearance

The long-term histological and virological outcomes of spontaneous circulating hepatitis C virus (HCV) clearance were studied in chronic liver disease. Between 1979 and 1984, three patients underwent laparoscopy for chronic non-A, non-B liver disease, and two were found to have cirrhosis and one with chronic active hepatitis. After HCV assays became available in 1990, they were positive persistently for HCV antibody without serum HCV RNA. Reductions of antibody levels to HCV core and/or nonstructural proteins were observed, and liver biopsies were undertaken between 1995 and 2000. Liver biopsies at 11-19 years after laparoscopy disclosed marked alleviation of liver inflammation and fibrosis in each case although a low grade of inflammation remained. The two patients with cirrhosis no longer showed histological features of cirrhosis, and the poor liver function in one patient had been ameliorated. Liver specimens from two patients were subjected to polymerase chain reaction to detect positive and negative HCV RNA strands and hepatitis B virus DNA. Only the positive HCV RNA strand was detected for one patient who had previously cirrhosis. Liver specimens were examined from another six nonviremic HCV-seropositive individuals without chronic liver disease. Five patients displayed low-grade liver inflammation without evident fibrosis, but none had any viral genome in the liver. These findings suggest that spontaneous circulating HCV clearance in chronic liver disease confers favorable liver histological outcome, although occult HCV infection persists. J. Med. Virol. 69:41-49, 2003.