Background. Nucleotide analogues (NTs) monotherapy may have a more significant 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). Therefore, this study aimed to explore whether NTs have more significant 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 after 48 weeks were analyzed. Results. A total of 95 patients were included and divided into the PegIFNα + NTs group and the PegIFNα + NSs group. Propensity score matching (PSM) was performed. The PegIFNα + NTs group had a greater reduction of HBsAg (−3.52 vs. −2.33 log₁₀ IU/mL, ) and a higher proportion of patients with HBsAg reduction >1 log₁₀ IU/mL (100.0% vs. 72.2%, ) 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. Subgroup analyses showed the difference in the reduction of HBsAg was particularly evident in HBeAg-positive and the “add-on” subgroups. PegIFNα plus NTs (OR = 36.667, 95% CI = 3.837–350.384) was an independent predictor for HBsAg reduction >1 log₁₀ IU/mL after 48 weeks. Conclusion. This study suggests that PegIFNα plus NTs may lead to more HBsAg reduction, especially in HBeAg-positive and “add-on” patients.

中文翻译：

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乙型肝炎表面抗原的减少在 PEG 化干扰素-α 联合核苷酸类似物治疗中可能比联合核苷类似物在慢性乙型肝炎患者中更显着：一项倾向评分匹配研究

背景。由于其免疫调节功能，核苷酸类似物 (NTs) 单一疗法在降低乙型肝炎表面抗原 (HBsAg) 方面可能比核苷类似物 (NSs) 具有更显着的效果。然而，当与聚乙二醇化干扰素α (PegIFN α ) 联合使用时，这种优势仍然未知。因此，本研究旨在探讨 NTs 与 PegIFN α联合治疗是否比 NSs 具有更显着的抗病毒作用。方法。回顾性招募了接受 PegIFN α加核苷（酸）类似物（NAs）治疗的慢性乙型肝炎（CHB）患者。乙型肝炎表面抗原 (HBsAg) 降低 >1 log _{10的疗效和预测因子}分析 48 周后的 IU/mL。结果。共纳入95例患者，分为PegIFNα +  NTs组和PegIFNα +  NSs组。进行了倾向得分匹配（PSM）。PegIFN α  + NTs 组的 HBsAg 降低幅度更大（-3.52 对比 -2.33 log ₁₀ IU/mL，)_{和更高比例的 HBsAg 降低 >1 log 10} IU/mL的患者（100.0% 对 72.2%，)即使在 PSM 之后。然而，HBsAg 和乙型肝炎 e 抗原 (HBeAg) 丢失率、HBeAg 血清转换率、HBeAg 和乙型肝炎病毒 (HBV) DNA 下降程度、HBV DNA 检测不到率和丙氨酸转氨酶 (ALT) 正常化率均无显着差异。亚组分析显示，HBsAg 降低的差异在 HBeAg 阳性和“附加”亚组中尤为明显。PegIFN α加 NTs（OR = 36.667，95% CI = 3.837–350.384）是 48 周后 HBsAg 降低 >1 log ₁₀ IU/mL 的独立预测因子。结论。这项研究表明，PegIFN α加 NTs 可能会导致更多的 HBsAg 减少，尤其是在 HBeAg 阳性和“附加”患者中。