Factors Predictive of Significant Hepatic Fibrosis in Adults With Chronic Hepatitis B and Normal Serum ALT

Goal: This study examines the prevalence and correlates of significant liver fibrosis among patients with immunotolerant hepatitis B. Background: Adults with chronic hepatitis B infection acquired early in life often have normal serum alanine aminotransferase (ALT) activity and high serum hepatitis B virus deoxyribonucleic acid loads (HBV DNA), known as "immunotolerant" hepatitis B. Study: We conducted a cross-sectional study of 28 hepatitis B patients with serum HBV DNA titer > 10 6 copies/mL, positive hepatitis B envelope antigen, and persistently normal serum ALT in a tertiary care setting. Liver biopsies were reviewed by a single pathologist who was blinded to other data. The prevalence of significant hepatic fibrosis was determined using the hospital-defined upper limit of normal for ALT and 2 more stringent criteria proposed by recent studies. Statistical analyses were conducted to identify factors associated with hepatic fibrosis. Results: The prevalence of stage 2 fibrosis using the hospital laboratory, more stringent, and most stringent definitions of normal serum ALT, was 32%, 32%, and 13%, respectively, corresponding to negative predictive values of 68%, 68%, and 88%, respectively. Age greater than 30 years (P = 0.035), grade 2 liver inflammation (P = 0.005), and lower serum HBV DNA level (mean 7.45 vs. 8.42 log 10 copies/mL, P<0.001) were independently associated with stage 2 fibrosis on liver biopsy. Conclusions: These results highlight the need to use stringent definitions of normal serum ALT when making clinical decisions for patients with chronic hepatitis B. Older age and lower serum HBV DNA level predict significant hepatic fibrosis on biopsy. Our findings may guide decisions regarding liver biopsy among patients with immunotolerant hepatitis B.