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

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 (I² = 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.