Single‐Arm Meta‐Analysis and Systematic Review on Clinical Cure of Chronic Hepatitis B After Haematopoietic Stem Cell Transplantation: Immunoregulatory Mechanisms and Clinical Translational Insights

Abstract

ABSTRACT The quest for a functional cure for chronic hepatitis B (CHB) remains an elusive objective. Haematopoietic stem cell transplantation (HSCT) may elicit viral clearance by immunological remodelling in recipients with positive HBsAg; however, the factors that determine its effectiveness are yet unknown. The aim of the study is to assess HSCT‐induced hepatitis B surface antigen (HBsAg) seroclearance rates and identify immunological mechanisms and combination therapy strategies through meta‐analysis and systematic review. In this study, nine trials (308 patients) were subjected to single‐arm meta‐analysis (R4.4.2 ‘meta’ package) in accordance with PRISMA/Cochrane criteria. Heterogeneity was addressed via random‐effects models ( I 2 = 87.1%). Subgroup analysis accounted for donor HBsAb/recipient HBeAg impacts. The total HBsAg clearance rate was 26% (95% CI: 14%–39%), greater than that of standard therapies. Notably, HBsAb‐positive donors had significantly enhanced clearance (55% vs. 8%, p < 0.01). HBeAg‐negative recipients fared better (29% vs. 2%). In patients who achieved HBsAg loss, HBsAb‐positive donors and HBeAg‐negative recipients are the most prevalent types (10/11). Sensitivity analyses confirmed robustness and publication bias was nonsignificant (Egger's p = 0.271). In conclusion, HSCT demonstrates the potential for functional cure in CHB, providing valuable insights into new immunological therapeutic strategies. More importantly, it serves as a powerful paradigm for identifying the immunological prerequisites for cure, informing the development of safer, targeted immunotherapies.