Efficacy of Antiviral Therapy in Chronic Hepatitis B Patients With Normal Alanine Aminotransferase: A Systematic Review and Meta-Analysis.

Background and objectives: The efficacy of antiviral therapy in chronic hepatitis B (CHB) patients with normal alanine aminotransferase (ALT) is controversial. This study aimed to systematically review and analyze antiviral efficacy in ALT-normal CHB patients. Methods: PubMed, Embase, Web of Science, and the Cochrane Library databases from inception to 17 May 2024 were searched for retrieving relevant studies with antiviral efficacy of ALT-normal CHB patients. Results: Of 4992 records screened, 10 studies met the criteria for inclusion and had a low risk of bias. The pooled proportions of undetectable HBV DNA, HBeAg loss, HBeAg seroconversion, HBsAg loss, and HBsAg seroconversion in ALT-normal CHB patients with antiviral therapy were 87%, 35%, 19%, 16%, and 10%, respectively. Subgroup analysis suggested that the virological and serological responses were better in patients receiving IFN-based therapy or with a longer follow-up time. Compared with no treatment, antiviral therapy was associated with significant higher rates of undetectable HBV DNA (RR: 65.62, 95% CI: 16.65-258.57, and p < 0.01), HBeAg loss (RR: 14.97, 95% CI: 3.31-67.65, and p < 0.01), HBsAg loss (RR: 14.22, 95% CI: 4.10-49.29, and p < 0.01), and HBsAg seroconversion (RR: 24.65, 95% CI: 3.06-198.60, and p < 0.01). The normal ALT group and elevated ALT group had comparable antiviral efficacy including proportions of undetectable HBV DNA, HBeAg loss, and HBeAg seroconversion (p > 0.05). Conclusions: CHB patients with normal ALT could benefit from antiviral therapy, and the virological and serological responses were comparable to that of ALT-elevated ones.