Hepatitis C virus infection and disease. Diagnostic problems.

Hepatitis C virus (HCV) is a lipid-enveloped single-stranded RNA virus with an unknown physical structure as only putative HCV particles have been identified by electron microscopy. Although HCV lacks the retroviral properties of being able to integrate into host DNA, it causes chronic infection in a considerable number of infected individuals (40-60%). Chronic infection is associated with a wide spectrum of liver diseases ranging from normal presentation to the different forms of chronic hepatitis, cirrhosis (about 20% of cases) and hepatocellular carcinoma. HCV therefore is not invariably and equally pathogenic, and genetic heterogeneity could be a major cause of such variability. Diagnosis of HCV infection relies on anti-HCV and HCV-RNA detection. Using second-generation assays, diagnostic sensitivity has increased to about 95%, but detection of anti-HCV does distinguish past from present infections. Only rising anti-HCV titres or anti-HCV seroconversion confirm a recent HCV infection. In anti-HCV-negative infections and cases of early acute hepatitis, HCV-RNA detection by RT-PCR represents a valid diagnostic alternative. In patients undergoing interferon therapy, testing for anti-HCV by immunoblotting represents a valid routine tool to monitor response. Anti-C-22 has the highest titre and persists longer while anti-C-100 is the earliest antibody to disappear in responders. The significant association between serum anti-C-100, HCV-RNA and liver disease suggests that anti-C-100 is an indirect marker of hepatitis C, but true markers of HCV-induced liver disease are still lacking.