Post-liver transplantation outcomes in acute-on-chronic liver failure: Impact of alcohol as a precipitant and etiology of chronic liver disease

Background: Acute-on-chronic liver failure (ACLF) has been associated with excellent post- liver transplant (LT) outcomes at one year, however the impact of alcohol as ACLF precipitant, specifically alcohol-associated hepatitis (AH), and as etiology of chronic liver disease (CLD) remains uncertain. This study aimed to assess the effect of alcohol as ACLF precipitant and CLD etiology (alcohol-associated liver disease (ALD) vs. non-ALD) on post-transplant outcomes. Methods: We performed a retrospective study using the Multi-Organ Dysfunction and Evaluation for LT Consortium database and included 640 patients with ACLF who underwent LT across 15 transplant centers in North America. The primary outcome was one-year post-transplant survival. We used logistic regression and Cox proportional hazards to compare post-transplant survival, mortality risk, and healthcare utilization, adjusting for age, ACLF grade, comorbid diabetes mellitus (DM), chronic kidney disease (CKD), and hepatocellular carcinoma (HCC). Results: Median follow-up from LT was 2.8 years (P25-P75, 2.2-5.5 y) for AH-ACLF (n=42) patients and 3.1 years (P25-P75, 1.6-4.9 y) for non-AH patients (n=598). No significant difference was observed in one-year survival post-LT in patients with AH-ACLF versus non-AH ( p =0.36). AH patients had significantly higher healthcare utilization evidenced by greater length of stay (28.5 vs. 19.0 d, p =0.004; adjusted linear estimate 16.89, 95% CI 7.66-26.11, p <0.001), higher rates of rehabilitation placement (71.4% vs. 41.8%, p =0.002; aOR 4.13, 95% CI 2.04 to 8.89, p <0.001), and non-ambulatory status (39.0% vs. 21.0%, p =0.005; aOR 4.54, 95% CI 1.90-10.79, p <0.001). Compared to other etiologies, ALD was not associated with differences in 1-year mortality, mortality risk over time, or healthcare utilization, after excluding patients with AH as ACLF precipitant. Conclusion: While there were no differences in one year survival, AH-ACLF was associated with higher healthcare resource utilization compared to other ACLF precipitants. Liver transplant centers should ensure adequate resources are allocated for management of these patients.