Virologic and Histologic Features of Chronic Hepatitis B Virus-Infected Asymptomatic Patients With Persistently Normal ALT

Background & Aims: There is a paucity of data on hepatitis B virus (HBV) DNA levels and histologic lesions in patients with chronic HBV (CHBV) infection and persistently normal alanine aminotransferase (ALT) levels (PNALT). We studied the ALT, HBV DNA levels, and spectrum of histologic lesions in such patients. Methods: One thousand three hundred eighty-seven incidentally detected asymptomatic hepatitis B surface antigen (HBsAg)-positive patients with ≥1-year follow-up and either PNALT (n = 189; hepatitis B e antigen [HBeAg⁺], 73; HBeAg⁻, 116) or persistently or intermittently elevated ALT (PIEALT; n = 1198; HBeAg⁺, 530; HBeAg⁻, 668) were included. Results: In the PIEALT and PNALT patients, baseline DNA ≥5-log copies/mL was seen in 73.8% and 60.3% in HBeAg⁺ (P = .018) and 76% and 35.3% in HBeAg⁻ (P < .001) patients and histologic fibrosis stage ≥2 in 65.5% and 40.2% in HBeAg⁺ (P < .001) and 63.9% and 13.8% in HBeAg⁻ (P < .001) patients, respectively. Approximately 21% of HBeAg⁻ patients with PNALT and HBV DNA <5-log copies/mL had histologically active liver disease (histologic activity index ≥3 and/or fibrosis stage ≥2). Conclusions: A fair proportion of patients with CHBV infection with PNALT have HBV DNA ≥5-log copies/mL and significant histologic fibrosis. Use of ALT and HBV DNA levels without resorting to liver biopsy to define “inactive carrier state” in HBeAg⁻ PNALT patients may miss histologically significant disease in a proportion of patients.

Abbreviations used in this paper: anti-HBe, antibody to HBeAg, CHBV, chronic hepatitis B virus, HBeAg, hepatitis B e antigen, HBsAg, hepatitis B surface antigen, IDAHS, incidentally detected asymptomatic HBsAg-positive subjects, PIEALT, persistently or intermittently elevated ALT, PNALT, persistently normal ALT