Natural history of hepatitis C virus carriers with persistently normal aminotransferase levels

Background & Aims: Some patients with serum hepatitis C virus (HCV) have pe rsistently normal aminotransferase (ALT) levels and are affected by cirrhos is. This study prospectively evaluated progression of the disease in a grou p of anti-HCV-positive patients with persistently normal ALT levels. Method s: Thirty-seven subjects were studied. Each subject underwent liver biopsy at baseline and after 5 years of follow-up, At baseline, serum samples were tested for genotypes and HCV RNA load. ALT levels and serum HCV RNA were t ested every other month and every 6 months, respectively. Patients with inc reased ALT were discharged from the study and treated with IFN. Five years after the end of IFN therapy, a liver biopsy was performed. Results: Liver biopsy at baseline showed chronic hepatitis in 34 patients and normal histo logy in 3 patients, 2 of whom were negative for HCV RNA and 1 positive. HCV genotypes were distributed as follows: 2a, 56%; Ib, 41%; and la, 3%, At th e end of 7-year follow-up, 73% of the patients still had normal ALT values, Liver histology after 5 years was comparable to that observed at entry to study. Conclusions: Most patients with persistently normal ALT serum levels have very mild chronic hepatitis. However, healthy anti-HCV-positive subje cts exist, In patients with HCV-related chronic hepatitis associated with p ersistently normal ALT levels, the grade of disease activity does not incre ase over years and progression to cirrhosis is slow or absent.