Abstract
Background: Nucleotide analogues (NTs) monotherapy may have a greater effect on reducing hepatitis B surface antigen (HBsAg) than nucleoside analogues (NSs) due to their immunomodulatory function. However, this superiority remains unknown when combined with pegylated interferon α (PegIFNα). The study aimed to explore whether NTs have greater antiviral effects than NSs in combination therapy with PegIFNα. Methods: Chronic hepatitis B (CHB) patients treated with PegIFNα plus nucleos(t)ide analogues (NAs) were retrospectively recruited. Efficacy and the predictors of hepatitis B surface antigen (HBsAg) reduction > 1 log10 IU/mL at 48 weeks were analyzed. Results: A total of 95 patients were investigated, including in PegIFNα plus NSs group and in PegIFNα plus NTs group. Propensity score matching (PSM) was performed. The PegIFNα + NTs group had a greater reduction of HBsAg (−3.48 vs −2.33 log10 IU/mL, P = 0.038) and a higher proportion of patients with HBsAg reduction > 1 log10 IU/mL (100.0% vs 72.2%, P =0.003) even after PSM. However, HBsAg and hepatitis B e-antigen (HBeAg) loss rates, HBeAg seroconversion rates, degree of HBeAg and hepatitis B virus (HBV) DNA decline, HBV DNA undetectable rates, and alanine aminotransferase (ALT) normalization rates showed no significant differences. Higher platelet counts (OR = 1.043, 95%CI = 1.002–1.085) and PegIFNα plus NTs (OR = 77.861, 95%CI = 3.923–1545.273) were independent predictors for HBsAg reduction > 1 log10 IU/mL at 48 weeks. Conclusion: This study suggests that PegIFNα plus NTs led to more HBsAg reduction.