Progressive hepatic fibrosis in healthy carriers of hepatitis C virus with a transaminase breakthrough.

In short-term studies, patients with chronic hepatitis C virus (HCV) infection, consistently normal serum aminotransferase (ALT) levels, and minimal or mild necro-inflammatory changes in the liver, did not progress to histologically severe hepatitis. There are no data on longer term outcome of liver disease in these patients. We describe two patients with HCV infection (genotype 2c) with a rise in serum ALT values greater than 10 times the upper normal value that occurred after an 8- and 15-year period of persistently normal or minimally elevated ALT levels. In both patients, the rise in ALT values lasted more than 16 weeks and was not associated with any symptom or risk factor for acute hepatitis. A liver biopsy performed 4 and 18 months after the ALT flare showed clear-cut progression from chronic hepatitis with mild activity to chronic hepatitis with severe activity and central to portal septal fibrosis (Ishak score: grading 14 and 6; staging: 4 and 5, respectively). Hence, extended surveillance of HCV carriers with consistently normal or minimally elevated ALT values is warranted as these patients are at risk of ALT flares and may develop progressive liver disease.