Abstract
BACKGROUND: Whether patients with chronic hepatitis B (CHB) with normal alanine aminotransferase (ALT) levels should receive antiviral therapy remains controversial. We compared the efficacy of nucleos(t)ide analogs (NAs) among CHB patients with different baseline ALT levels. METHODS: A total of 1,204 treatment-naïve CHB patients with detectable hepatitis B virus (HBV) DNA levels who initiated first-line NAs treatment were retrospectively included from three hospitals and followed up for 96 weeks. Virological response (VR) and HBeAg serological responses were compared among patients with different baseline ALT levels. RESULTS: Of the total patients, 682 (56.6%) were HBeAg-positive at baseline. In patients with normal ALT levels, 44.9% and 69.4% of HBeAg-positive patients achieved VR at weeks 48 and 96, respectively, whereas VR rates were 91.2% and 91.9% in HBeAg-negative patients, respectively. In the multivariate Cox regression analysis, baseline ALT ≤ 1×upper limit of normal (ULN) and ALT 1-2×ULN were not associated with VR compared to ALT > 2×ULN. However, the cumulative incidence of HBeAg clearance and seroconversion was significantly lower in patients with ALT ≤ 1×ULN than in those with ALT > 2×ULN (both P < 0.001). Baseline ALT ≤ 1×ULN was associated with a significantly lower chance of achieving HBeAg clearance (HR = 0.314, 95% CI: 0.163-0.607, P = 0.001) and HBeAg seroconversion (HR = 0.280, 95% CI: 0.127-0.615, P = 0.002). CONCLUSIONS: CHB patients with normal ALT levels had comparable VR rates but significantly lower rates of HBeAg clearance and seroconversion during first-line NA therapy than patients with elevated ALT levels.