Liver histology and progression of fibrosis in individuals with chronic hepatitis C and persistently normal ALT

Abstract

Objective: The natural history of hepatitis C virus (HCV) infection in patients with normal liver biochemistry remains poorly characterized. We performed a retrospective review of patients with chronic HCV infection and persistently normal ALT to compare clinical and histological features with those in patients with abnormal liver biochemistry.

Methods: Ninety-one HCV RNA-positive patients with persistently normal ALT who had a liver biopsy between 1993 and 1999 were identified. Clinical, histological, and epidemiological features in this group were compared with those found in 94 patients with abnormal ALT. Biopsies were assessed using Ishak's scoring system and fibrosis progression rate calculated from the likely time of infection.

Results: Although overall necroinflammatory score and fibrosis were significantly lower in those with normal ALT, none had normal liver histology, and 15 (16%) patients with normal ALT were found to have significant necroinflammation with a score of 5 or greater and/or significant fibrosis staged at 3 or 4. No clinical, epidemiological, or virological predictors of severe histological disease were found.

Conclusions: One in six patients with HCV infection and persistently normal ALT will have evidence of significant, progressive liver disease that can only be identified on liver biopsy.