Circulating soluble Fas levels in patients with hepatitis C virus infection and interferon therapy.

BACKGROUND: The clinical relevance of the circulating soluble form of the Fas-Receptor (sFas) was investigated in patients with hepatitis C receiving type 1 interferon (IFN) therapy. METHODS: sFas was quantified by enzyme-linked immunosorbent assay in 66 hepatitis C virus (HCV) carriers and 30 HCV-naive or previously infected controls. The levels were then monitored during enhanced treatment with type 1 IFNs in 15 chronic hepatitis C patients. RESULTS: The HCV carriers had high levels of sFas compared with controls (3.8+/-1.3 vs 2.7+/-0.8 ng/ml; P<0.001). sFas levels in patients with chronic HCV infection were directly related to serum alanine aminotransferase levels (r=0.440; P<0.001) and the histological grade (r=0.403; P=0.019). Among necroinflammatory reactions, only piecemeal necrosis showed a correlation with sFas levels (r=0.556; P=0.001). Pretreatment sFas levels, however, were not predictive of therapeutic outcomes. A sustained virological response to enhanced IFN therapy showed a relation to only the pretreatment HCV load. Interestingly, circulating sFas was upregulated when IFN-beta was administered at short intervals (3 MU/every 12 h). This upregulation was accompanied by parallel aminotransferase elevation, which was observed regardless of a virological response. CONCLUSIONS: sFas elevation, in parallel with the severity of liver injury, suggests the possible upregulation of hepatic Fas expression and the Fas-mediated pathway in both HCV- and type 1 IFN-induced liver injury. The essential function of sFas to protect hepatocytes against Fas-mediated liver injury was not evident in these clinical settings.

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.