The clinical significance of persistently normal ALT in chronic hepatitis B infection

Background/Aims: Chronic hepatitis B virus (HBV) disease is caused by both necroinflammation and active viral replication. The role of ALT levels as a predictor of liver injury has recently been questioned. The aim of the study was to determine whether normal ALT is associated with liver injury in a cohort of HBV patients undergoing liver biopsy. Methods: This is a retrospective review of chronic HBV patients divided into 3 groups; (1) persistently normal ALT (PNALT); (2) ALT 1-1.5X ULN and (3) ALT > 1.5X ULN. Multiple clinical, biochemical, virological variables were evaluated. Results: One hundred and ninety-two patients met the inclusion criteria, 59 with PNALT, 26 with ALT 1-1.5X ULN, and 107 with ALT > 1.5X ULN. Increasing age, higher ALT, higher grade of inflammation on biopsy, and HBeAg positivity predicted fibrosis. 18% of patients with PNALT had stage 2+ fibrosis and 34% had grade 2 or 3 inflammation. Overall 37% of patients with PNALT had significant fibrosis or inflammation. Subgroup analysis showed the majority with fibrosis belonged to the high normal ALT group and that only a minority who were young and immune tolerant had significant findings on biopsy. Conclusions: There is significant fibrosis and inflammation in 37% of patients with PNALT and a liver biopsy should be considered in patients older than 40 with high normal ALT. (c) 2007 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.