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.