Metabolic dysfunction-associated steatotic liver disease correlates with higher lower graft survival in liver transplant recipients with hepatocellular carcinoma.

Background: Direct-acting antivirals (DAAs) have revolutionized hepatitis C virus (HCV) treatment. The changing landscape of hepatocellular carcinoma (HCC) in liver transplant (LT) recipients lacks a thorough description of the outcomes of HCC based on etiology.

Objective: To assess the waitlist (WL) dropout and graft survival in HCC LT candidates based on the etiology of HCC in the post-DAA era.

Methods: This retrospective cohort study analyzed United Network Organ Sharing/Organ Procurement Transplant Network data from 2015 to 2022. Graft survival was analyzed using Kaplan-Meier curves, and predictors of WL dropout and graft failure were assessed using multivariate analysis.

Results: Among LT recipients, etiologies were HCV (53.6%), alcohol-associated liver disease (ALD) (12.0%), metabolic dysfunction-associated steatotic liver disease (MASLD) (16.6%), hepatitis B virus (HBV) (5.6%), and other (12.1%). MASLD and ALD had the highest dropout rates (1-year: 20.4%, 21.7%; 3-year: 58.2%, 51.1%; P  < 0.001). Dropout was linked to diabetes, low albumin, high Model of End-Stage Liver Disease, high alpha-fetoprotein, tumor number, and size. MASLD had the worst 1-, 3-, and 5-year graft survival (89.8%, 81.8%, and 74.1%) and higher failure risk than HCV (hazard ratio: 1.143, 95% CI: 1.021-1.281). Diabetes negated MASLD's impact on graft failure but worsened survival for MASLD-HCC compared with HBV and ALD, matching HCV.

Conclusions: MASLD has the highest WL dropout and post-LT graft failure among HCC LT candidates, surpassing HCV in the post-DAA era. The worst graft survival in MASLD-HCC is associated with pre-LT diabetes.