Is serum alanine transaminase level a reliable marker of histological disease in chronic hepatitis C infection?

Background: Approximately 20-30% of patients chronically infected with hepatitis C virus (HCV) have persistently normal alanine transaminase (PNALT) levels. These patients are described to have a mild degree of histological liver damage. We aimed to assess the histological liver changes in HCV patients with PNALT.

Patients And Methods: Sixty-five patients with HCV and PNALT (group A) underwent a liver biopsy. PNALT was defined as three or more determinations identified to be within the normal range over 6 months or longer. The demographical features and histological changes were compared with 66 consecutive patients with chronic HCV infection and elevated ALT (group B). All patients had a detectable HCV RNA. Histological disease was scored according to the METAVIR system.

Results: Females were more likely to have normal ALT levels (65%). The mean ALT level in Group A and B was 30 and 105 IU/L respectively. No patient in either group had normal histology. The mean necro-inflammatory scores in groups A and B (2.0+/-0.68 vs 2.09+/-0.67) and the mean fibrosis scores (2.11+/-0.87 vs 2.24+/-1.04) were not significantly different. Bridging fibrosis in groups A and B was seen in 24.6 and 37.9% patients, respectively, while cirrhosis was seen in 6.2 and 7.6% patients respectively. Hepatic steatosis in groups A and B (0.94+/-0.86 vs 1.0+/-1.02 respectively) was also not significantly different and did not show any association with the fibrosis scores across the two groups. In group A, the necro-inflammatory and fibrosis scores of patients with and without steatosis were not statistically significant. Age was the only predictor of normal ALT levels. However, increasing age did not show a significant increase in histological activity in either group beyond a certain age.

Conclusion: This study demonstrates that ALT is a poor surrogate marker for inflammation and fibrosis in HCV patients. Given the presence of significant necro-inflammation in PNALT patients, the risk/benefit ratio justifies treatment without the need for a liver biopsy.