NASH vs. Non-NASH HCC within and Beyond Milan Criteria in Liver Transplantation for Hepatocellular Carcinoma

Abstract

Introduction: With mounting obesity, non-alcoholic steatohepatitis (NASH)-associated hepatocellular carcinoma (HCC) is a rising indication for HCC-related liver transplantation (LT). This unique population, often with multiple comorbidities, has potential for worse outcomes post-LT. The study aims to compare post-transplantation overall survival (OS) of NASH HCC versus non-NASH HCC patients using a large, North American cohort. Methods: Adults who received primary LT for HCC between 2008-2018, from the United Network for Organ Sharing transplant registry (UNOS) and University Health Network (UHN) database, were included. Two populations were defined: NASH HCC and non-NASH HCC. Recipient characteristics, transplant-specific variables, post-transplant survival outcomes, and causes of death were compared. Sensitivity analyses were performed for populations within and beyond Milan criteria. Results: 20,709 patients were transplanted for HCC, with 2,075(10.0%) NASH HCC. The proportion of LT for NASH HCC increased annually (P=0.02 UHN, P<0.001 UNOS). NASH HCC patients were older, more often female, had higher body mass index, and higher pre-transplantation model for end-stage liver disease score. The 1-, 3-, and 5-year OS were 90.7%, 83.9%, and 76.3% NASH-HCC versus 91.9%, 82.1%, and 74.9% non-NASH HCC (P=0.89). No OS differences were observed within and beyond Milan. Cardiovascular causes contributed to a greater proportion of deaths in NASH HCC (P<0.001). There were no differences in malignancy- or HCC recurrence-related deaths. Conclusion: The global obesity epidemic will have significant future implications in LT and organ allocation. Despite demographic differences, no post-transplantation survival differences exist between NASH and non-NASH HCC. This justifies equivalent organ allocation, irrespective of NASH status.