Intention-to-treat approach for survival benefit of ABO-incompatible living-donor liver transplantation in patients with high Model for End-stage Liver Disease scores

Abstract

Background: ABO-incompatible (ABOi) living-donor liver transplantation (LDLT) is increasingly considered for patients with end-stage liver disease or hepatocellular carcinoma, in regions facing severe organ shortage. However, its applicability for patients with high Model for End-stage Liver Disease (MELD) scores remains uncertain. We aimed to investigate the survival benefit of ABOi-LDLT in high MELD patients using intention-to-treat (ITT) analysis in retrospective cohort study. Methods: In a single-center study, 649 patients on a liver transplantation (LT) waitlist were divided into three groups: ITT-ABOi-LDLT (n=45), ITT-ABO-compatible (ABOc)-LDLT (n=162), and ITT-deceaseddonor LT (DDLT) (n=442). Results: The ITT-ABOi-LDLT group had a median initial isoagglutinin-titer of 1:128 and 71.1% underwent ABOi-LDLT after desensitization. This group showed a higher survival rate compared to ITTDDLT (66.7% vs. 28.7%, P<0.001), and ABOi-LDLT intention was linked to significantly lower mortality (hazard ratio, 0.32; P<0.001). Survival among LT recipients was similar across ABOi-LDLT, DDLT, and ABOc-LDLT (P=0.13), but ABOi-LDLT recipients had higher biliary stricture rates compared to DDLT (25% vs. 10%, P=0.04). Donor postoperative outcomes were comparable between ABOi- and ABOc-LDLT. Higher initial isoagglutinin-titers in ABOi-LDLT recipients were associated with increased in-hospital mortality and graft loss but not with antibody-mediated rejection or isoagglutinin-titer rebound. Conclusions: ABOi-LDLT offers a viable option for high MELD score patients, improving survival compared to DDLT and yielding similar posttransplant outcomes to DDLT and ABOc-LDLT in severe organ shortage region.