Hepatitis B surface antigen clearance rate with pegylated interferon-α therapy in different chronic hepatitis B virus infection populations: A systematic review and meta-analysis

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Abstract Background: Chronic hepatitis B virus (HBV) infection is an urgent public health issue, particularly in endemic regions of Asia and sub-Saharan Africa. Achieving hepatitis B surface antigen (HBsAg) clearance significantly reduces the risk of hepatocellular carcinoma. Pegylated interferon alpha (PegIFNα) is widely recognized as the preferred treatment. However, the efficacy of PegIFNα in different chronic HBV infection populations has not been systematically evaluated. This study aimed to assess the HBsAg clearance rate of PegIFNα in different chronic HBV infection populations and to identify influencing factors. Methods: A systematic search was conducted in PubMed, EMBASE, the Cochrane Central Register of Controlled Trials, and the Web of Science from inception through September 28, 2022, with an update on December 6, 2023. Demographic characteristics, HBsAg clearance, and seroconversion rates were analyzed in different chronic HBV infection populations. Subgroup analyses and meta-regression were performed to explore factors influencing HBsAg clearance. Results: Of the 4867 studies screened, 115 were included in the meta-analysis. The overall HBsAg clearance rate with PegIFNα-based therapy across different chronic HBV infection populations was 16% (95% confidence interval [CI]: 13–20%). The HBsAg clearance rates at the end of treatment (EOT) were 5% (95% CI: 4–7%) in treatment-naive chronic hepatitis B (CHB) patients, 21% (95% CI: 16–26%) in nucleos(t)ide analogues (NAs)-treated CHB patients, 57% (95% CI: 48–65%) in inactive HBsAg carriers, and 22% (95% CI: 10–37%) in children with CHB. The infection population was identified as a key factor influencing HBsAg clearance and seroconversion. Conclusions: PegIFNα significantly enhances HBsAg clearance in different chronic HBV infection populations, particularly in NAs-treated patients, inactive HBsAg carriers, and children with CHB, achieving higher rates than observed with spontaneous clearance and long-term NAs therapy. Registration: PROSPERO; No. CRD2024604070.