Association of donor heavy alcohol use with graft failure after deceased-donor liver transplantation stratified by donor sex and macrosteatosis in the OPTN/UNOS registry

A subset of deceased liver donors have a history of heavy alcohol intake. We evaluated whether donor heavy alcohol history is associated with graft failure after liver transplantation (LT) and whether associations differ by donor sex and macrosteatosis. We conducted a retrospective cohort study using the OPTN/UNOS registry, including 29,170 adult LT recipients (2000–2023). The exposure was heavy alcohol intake (> 2 drinks/day). The primary outcome was graft failure. Associations were estimated using Cox proportional hazards models adjusted for donor, recipient, and transplant covariates. The proportion of donors with heavy alcohol history increased over time (2000–2007, 19.0%; 2008–2015, 20.3%; 2016–2023, 22.3%). In multivariable analyses, donor heavy alcohol history was not associated with graft failure overall (HR = 0.96 [0.90–1.03], P = 0.249). Donor macrosteatosis was independently associated with higher risk (HR = 1.07 [1.01–1.13], P = 0.020). Associations differed by donor sex: among female donors, heavy alcohol history was associated with lower graft failure risk (HR = 0.87 [0.77–0.98], P = 0.010), whereas no association was observed among male donors (P = 0.802). The lower risk seen with female donors was not present when donor livers had macrosteatosis (P = 0.271). In conclusion, donor heavy alcohol history was not associated with increased graft failure risk overall. Notably, grafts from female donors with a heavy alcohol history were associated with lower failure risk, an apparent advantage that was not observed in the presence of macrosteatosis. No association was observed among male donors. These findings suggest sex- and liver-quality–dependent heterogeneity in the relationship between donor alcohol history and post-transplant outcomes.