UTILITY OF HEPATITIS-C VIRUS-RNA DETERMINATIONS IN HEPATIC TISSUE AS AN END-POINT FOR INTERFERON TREATMENT OF CHRONIC HEPATITIS-C

A total of 41 patients with chronic hepatitis C virus (HCV) defined as abnormal liver injury test results for 6 months or more and HCV RNA p ositivity in plasma were studied to determine if the liver might not b e the only focus of HCV infection in individuals treated with interfer on alfa (IFN-alpha). All patients were examined for the presence of co nfounding liver disease and tested negatively for such findings, All t ested positively for HCV RNA and had an abnormal hepatic histology. Al l were treated with IFN for 6 months at a dosage of 5 million units da ily, After 6 months of therapy, 29 (71%) had normal alanine transamina se (ALT) values, and 25 (61%) tested negatively for HCV RNA. After 6 m onths of follow-up, without IFN therapy, 17 (41%) still had normal ALT values, and 16 (39%) still tested negatively for HCV RNA in serum, Pa tients who continued to test negatively for HCV RNA in serum after 6 m onths of follow-up also tested negatively for HCV RNA in the liver at the end of IFN therapy. Only 2 subjects who tested negatively for HCV RNA in the liver at the end of treatment relapsed after discontinuing IFN therapy. In contrast, patients who tested positively for HCV RNA i n the liver after 6 months of therapy relapsed and tested positively f or HCV RNA in serum during the 6 months of follow-up. These results su ggest that (1) a nonhepatic site of HCV infection may exist; (2) this putative extrahepatic site appears to be less responsive to IFN therap y than in the liver; and (3) this unknown extrahepatic site of infecti on may be the source of HCV reactivation in cases that relapse during IFN follow-up periods.