Liver donor macrosteatosis is associated with adverse long-term outcomes exclusively in metabolic dysfunction-associated steatotic liver disease recipients: a U.S. transplant registry analysis over the last decade.

BACKGROUND: Liver grafts with >30% macrovesicular steatosis (Mas30) have shown acceptable long-term graft survival (GS) in steatotic liver disease (SLD) recipients. However, grouping SLD etiologies under a single umbrella ignores their distinct metabolic profiles and may lead to suboptimal allocation decisions. Considering the 2023 Delphi consensus nomenclature, we aimed to compare early and long-term GS following Mas30 liver transplantation (LT) across SLD subtypes. METHODS: We analyzed adult LT recipients in the U.S. national transplant registry from 2014 to 2024. Donor macrovesicular steatosis was categorized as none (<5%), mild (5-30%), and Mas30 (>30%). SLD recipients were classified as metabolic dysfunction-associated steatotic liver disease (MASLD), metabolic dysfunction and alcohol-related liver disease (MetALD), or alcohol-associated liver disease (ALD). Primary endpoints were early (90-day) and long-term (3-year) GS. Time-to-event analyses were conducted using Kaplan-Meier and multivariable Cox regression. RESULTS: Among 27,164 LT recipients (14,270 SLD and 12,894 non-SLD), Mas30 utilization declined over time (P<0.001). MASLD recipients of Mas30 grafts had reduced early GS (87.8% vs. 93.6% mild vs. 95.3% none; P<0.001) and long-term GS (83.0% vs. 86.6% vs. 87.5%; P=0.01). After adjustment, Mas30 grafts conferred nearly threefold higher early failure risk [adjusted hazard ratio (aHR) 2.93, P<0.001] and persistent long-term risk (aHR 1.66, P=0.002). No association was observed in MetALD or ALD recipients (all P>0.17). Sensitivity analyses including competing risk models confirmed these findings (MASLD: early sHR 3.18, P=0.001; long-term sHR 2.18, P=0.01). CONCLUSIONS: MASLD recipients receiving Mas30 grafts experience substantially reduced GS extending to 3 years post-LT, while MetALD and ALD recipients remain unaffected. Our findings support etiology-specific allocation strategies for steatotic liver grafts.