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Efficacy of NAs in combination with Peg-IFN for functional cure in patients with CHB: a meta-analysis of RCTs.

Yaqin Zhang·Ziyu Zhang·Xinxin Li·Weihua Cao·Shiyu Wang·Wen Deng·Xin Wei·Linmei Yao·Yao Xie·Minghui Li
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Abstract

BACKGROUND: The goal of treating chronic hepatitis B (CHB) is to achieve functional cure. We aimed to evaluate the efficacy of the combination of nucleoside (acid) analogues (NAs) and pegylated interferon (Peg-IFN) on the functional cure of CHB patients at the EOT and at the EOF. METHOD: PubMed, Embase, and Web of Science were searched systematically up to March 15, 2025. Sixteen RCTs on CHB patients receiving combination or monotherapy were included. RESULT: Compared with NAs treatment, the NAs combined with Peg-IFN treatment group significantly improved HBsAg clearance rate (RR: 14.05, 95% CI 6.13-32.20) and HBsAg seroconversion rate (RR: 12.82, 95% CI 5.08-32.33) at the EOT. Moreover, compared with NAs treatment, the NAs combined with Peg-IFN treatment group significantly improved HBsAg clearance rate (RR: 7.70, 95% CI 4.24-13.98), HBsAg seroconversion rate (RR: 11.93, 95% CI 5.14-27.67) at the EOF. However, compared with Peg-IFN monotherapy, the combination therapy group did not show any improvement in HBsAg clearance rate, HBsAg seroconversion rate, and the rate of qHBsAg decrease > 1 log10 IU/mL at the EOT and the EOF. Moreover, in terms of safety, the Peg-IFN monotherapy group showed more ALT flares (ALT > 5 × ULN) during the treatment process. CONCLUSION: Compared with NAs therapy, Peg-IFN combined with NAs therapy significantly improves functional cure rate. However, combination therapy shows no additional advantage over Peg-IFN monotherapy in achieving functional cure. The Peg-IFN monotherapy group has a higher incidence of ALT flares than the combination therapy group.

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HumansAntiviral AgentsDrug Therapy, CombinationHepatitis B Surface AntigensHepatitis B virusHepatitis B, ChronicInterferon-alphaNucleosidesPolyethylene GlycolsRandomized Controlled Trials as TopicRecombinant ProteinsTreatment OutcomeChronic hepatitis Binterferonnucleoside analoguestherapeutic effectJournal ArticleMeta-AnalysisSystematic ReviewResearch Support, Non-U.S. Gov't

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Yaqin Zhang, Ziyu Zhang, Xinxin Li, Weihua Cao, Shiyu Wang, Wen Deng, Xin Wei, Linmei Yao, Yao Xie, Minghui Li. 2026-03-04. Efficacy of NAs in combination with Peg-IFN for functional cure in patients with CHB: a meta-analysis of RCTs.. https://doi.org/10.1080/07853890.2026.2636319

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Drug Therapy, Combination subjectHepatitis B Surface Antigens subjectHumans subjectJournal Article subjectMeta-Analysis subjectSystematic reviews study

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