Disease etiology matters: Divergent post-transplant outcomes in ACLF across primary liver diseases

Background & Aims Acute-on-chronic liver failure (ACLF) is associated with high short-term mortality. Liver transplantation remains the only definitive therapy; however, persistent organ scarcity emphasizes the need to better identify patients most likely to benefit. The long-term post-transplant prognosis of ACLF patients across different underlying liver disease etiologies remains poorly characterized. Methods This study included data from the United Network for Organ Sharing (UNOS) Standard Transplant Analysis and Research (STAR) Database, encompassing liver transplant (LT) recipients spanning from 2005 to 2019. Patients were segmented into distinct groupings: those without ACLF (control) and those with ACLF grades 1, 2, and 3 (exposures), as per the EASL-CLIF criteria. Primary outcomes encompassed post-transplant graft failure and all-cause mortality. Secondary outcomes included mortality attributed to specific organ system failures. Results Among 36,748 liver transplant recipients, increasing ACLF severity was associated with higher post-LT all-cause mortality across most liver disease etiologies. Alcohol-associated liver disease (ALD), hepatitis C, and metabolic dysfunction–associated steatotic liver disease (MASLD) exhibited increased all-cause mortality across all ACLF grades. Autoimmune hepatitis (AIH) and hepatitis B demonstrated increased mortality primarily in advanced ACLF (AIH G3: aHR 1.53, 95% CI 1.25–1.86, p