Project Summary Alcoholic liver disease (ALD) is among the most common indications for liver transplant (LT), accounting for over 30% of LTs performed annually in the United States. Given concerns for post‐transplant recidivism, transplant centers have required 6 months of documented sobriety prior to LT. However, a subset of patients present for medical care with severe alcoholic hepatitis (SAH), requiring urgent and aggressive medical management. If they are unresponsive to medical treatment, LT is the only life‐saving option. Without LT, SAH patients have a 70‐80% three‐month mortality, therefore a 6‐month sobriety rule precludes most patients from life‐saving LT. We have demonstrated that early LT (ELT) for SAH provides excellent short‐term survival and similar recidivism rates in comparison to LT for ALD with 6 months sobriety. ELT for SAH is rare and controversial, because at many centers, the standard 6‐month sobriety period is a transplant candidacy requirement. However, critics of this requirement emphasize that an unreliable predictor of recidivism. In order to minimize risk to the public perception, careful analysis of ELT selection criteria is crucial to ensure allocation to those with the greatest survival benefit and highest chance of maintained sobriety. Ethically sound candidate selection criteria is paramount to identifying SAH patients who would significantly benefit from ELT. In this study we will identify social determinants of health (SDoH) affecting access to ELT and assess how SDoH impact short- as well as long-term outcomes in ELT. We will also determine the ethical issues surrounding the practice by evaluating stakeholder opinions regarding ELT for SAH, in an effort to develop a comprehensive national policy. Further, we will examine recidivism in ELT recipients, comparing differing behavioral and pharmacologic interventions to identify mitigating strategies. We will also continue the study of explanted livers from patients undergoing transplant to identify the molecular-level changes characterizing the pathophysiology of SAH. Lastly, we seek to utilize small animal models of liver transplantation in conjunction with alcohol exposure to answer questions about liver regeneration, and the immune system that cannot be answered directly from our patients. This work is now being conducted under the auspices of our “DELTA Center” (Delivery of Early Liver Transplant for Alcoholic Hepatitis) at Johns Hopkins. The identification of SDoH that affect access to ELT for will provide actionable areas for improving delivery of this service to the most disadvantaged of an already vulnerable population. The ethical insight from stakeholders will aid in the development of a national policy for the practice, and insights gained from investigation of post-transplant recidivism interventions, explant pathology, as well as animal models of SAH, will provide us with a more comprehensive understanding of the disease pathophysiology and managemen...