Alcohol consumption is a major cause of liver disease worldwide. Severe alcoholic hepatitis (SAH), an acute manifestation of alcohol-related liver disease (ALD), is associated with inferior short-term survival. Unfortunately, there are few effective medical therapies for SAH outside of corticosteroids, to which about 40% of patients are refractory. For these patients, liver transplantation (LT) is the only rescue treatment available. Until recently, most transplant centers mandated at least six months of continuous abstinence from alcohol before LT. Unfortunately, this ?6-month rule? was(is) often unachievable for patients with SAH, due to recent alcohol use and high short-term mortality. Several recent studies from Europe and the United States championed the concept of early liver transplantation (ELT) in this highly vulnerable patient cohort, though post-LT alcohol relapse remained a concern with adverse consequences like graft injury and cirrhosis. To date, there is no consensus on the optimal LT candidate selection criteria in ALD, which can lead to uneven and substandard post-LT outcomes, including alcohol relapse. This project will advance our field in several ways. First, it will define the impacts of ELT and alcohol abstinence on the natural history of SAH. Second, it will develop and validate a novel LT candidate selection tool in ALD. The project findings will support a planned multicenter trial and R01 submission for the external evaluation of the candidate selection tool. This proposed work represents an interdisciplinary approach toward the optimization and the standardization of the LT candidate selection process in ALD. To conduct this study, I will integrate myself into the research community of the NIAAA P50-funded Johns Hopkins DELTA Center for Alcohol Research, which will help me establish a network of alcohol researchers for current and future collaboration. I will also actively engage in formal coursework in biostatistics and addiction science as well as interdisciplinary career development programs. Through the proposed career development plan, I will gain the necessary skills and experience to establish myself as an independent clinical investigator bridging the fields of hepatology, transplantation, and addiction medicine.
Alcohol-related liver disease (ALD), from chronic cirrhosis to acute alcoholic hepatitis, is now the leading indication for liver transplantation in the United States. However, there is no consensus on the optimal transplant candidate selection criteria, and center-specific practices remain the norm. This project will 1) study the impacts of liver transplant and sobriety on survival in alcoholic hepatitis and 2) identify the ideal predictors of post-transplant outcomes in ALD. The study findings will help establish standardized and transparent liver transplant candidate selection in ALD across the United States.
