Project 1-Cohort/Ethics Study of Patients with Severe Alcoholic Hepatitis undergoing Early Liver Transplantation

Project Summary In 2021, Alcoholic Liver Disease (ALD) accounted for 37% of liver transplants (LTs) performed in the United States. Given concerns for relapse in alcohol use post-transplant, most centers require that candidates have been abstinent from alcohol use for 6-months prior to being placed on the waitlist for transplant. However, a subset of patients present with severe alcoholic hepatitis (SAH) refractory to medical management and with a 3-month mortality of 70-80% without LT. This dire situation precludes the possibility of a 6-month wait period. Early LT (ELT) is the only life-saving treatment available for these patients, however, access to this practice is limited, due to a lack of national consensus on criteria for listing and transplant. We conducted a pilot study of ELT for SAH. In our initial experience, candidates with SAH who underwent liver transplant prior to a 6-month wait achieved demonstrated excellent 1-year post-transplant survival and had identical rates of relapse when compared to LT recipients with 6-month sobriety. Based on these encouraging findings, we established the DELTA Center (Delivery of Early Liver Transplant for Alcoholic Hepatitis) at Johns Hopkins University as a specialized alcohol research center. The DELTA center has accrued the world’s largest cohort of candidates with SAH and ELT recipients in the world. Despite excellent outcomes post- transplant, we have transplanted a relatively homogenous group of ELT recipient with regards to sociodemographic factors and it has become clear that access to ELT may not be equitable. Continued work through our DELTA Center will now focus on continued expansion of ELT with a focus on understanding the impact of social determinants of health (SDoH) on access and outcomes in ELT. We will leverage the resources and experience of the DELTA Center and engage relative stakeholders to build an ethical framework for ELT that can guide dissemination of this practice to other transplant centers. We propose: 1) To identify SDoH associated with access to ELT; 2) To quantify longer-term post-transplant outcomes for ELT, up to 10- years; 3) to identify SDoH associated with post-transplant outcomes assess; and 4) To establish an ethical framework for considering ELT for SAH based on the opinions of SAH patients, transplant providers, and the general public about this practice, ultimately resulting in a new rational national policy on ELT for SAH. This study represents the largest and longest prospective cohort study of ELT for SAH. Our findings will have an immediate and direct impact on the practice of ELT for SAH in the United States, informing critical aspects of candidate selection, overcoming barriers to access, informed consent, post-LT care and national policy. Robust quantification of the impact of SDoH on ELT for SAH is novel and necessary to ensure equity. A better understanding of this emerging treatment is essential for improving care of patients with SAH and will help improve the feasibility, availability and quality of care we provide to this vulnerable patient population.