Alcohol-associated liver disease accounts for 50% of liver-related deaths, and its rates are rising worldwide. But one of the best treatment options, early liver transplantation (ELT)-; transplants done with no mandatory period of abstinence from alcohol-; is also one of the most controversial, partly because of concerns that patients will relapse to alcohol after transplantation.
Part of the problem is that livers for transplants are in short supply, and researchers lack data to determine who will benefit most from ELT. Studies show that decisions about who gets a transplant can, at times, be influenced by bias or unsystematic. The result is that many patients lack access to life-saving care, while others continue to have poor health even after getting a transplant.
There are significant knowledge gaps that contribute to disparities in access to transplant, as well as post-transplant outcomes. Early transplant for alcohol-associated liver disease is now the fastest-growing reason for liver transplants, so there’s a real urgent need for more data.”
Brian P. Lee, MD, assistant professor of clinical medicine in gastrointestinal liver diseases, Keck School of Medicine of USC
To that end, Lee and his collaborators have just received $12 million from the National Institutes of Health for a seven-year study of ELT. Lee, his co-principal investigator, Norah Terrault, MD, professor of medicine, chief of the Division of GI and Liver and Neil Kaplowitz Chair in Liver Diseases at the Keck School of Medicine, and their collaborators will recruit participants from nine sites across the country through their ACCELERATE consortium.
The team will then collect a broad range of data, including audio recordings that document how patients are selected for ELT, information about patient outcomes, and biological samples that will be used to create a repository of data on alcohol and liver health. By the end of the funding period, the researchers aim to understand how to offer ELT fairly and effectively, both based on patient characteristics and through a more systematic approach to selection.
“Our goal is to help stem an epidemic of alcohol-associated liver disease and to provide our patient community with better treatment options,” Lee said.
Overcoming health disparities
Decisions about who receives an organ transplant are not always fair. Studies show that factors such as race, socioeconomic status and insurance type (public versus private) impact both transplant access and health outcomes following the operation.
Lee and his colleagues are taking a close look at the selection process to get a better sense of where bias enters the equation. First, they’re comparing socioeconomic status-;based on a patient’s home address-;to transplant selection decisions. They’re also collecting audio recordings during the transplant selection process to determine key factors influencing selection decisions. The insights they gain can aid in the development of best practices and checklists to reduce systematic bias. At the patient level, they’re analyzing data on insurance type, income and other social determinants of health.
Patients will be recruited at nine sites across the country from a variety of demographic groups, ensuring diversity of gender, age, race/ethnicity, education level, income level and geographic region that reflects the full scope of patients who receive liver transplants. At the Keck School of Medicine, the majority Hispanic patient population provides a unique opportunity to study how best to serve a group traditionally underrepresented in medical research, Lee said.
Building a biorepository
In addition to analyzing the selection process, the researchers will collect data on what happens after selection, with the goal of improving transplant outcomes for patients. After a transplant, what factors predict alcohol relapse and what factors predict survival? What therapies are most effective for preventing and treating alcohol relapse? Do patients develop cardiovascular problems, cancer or other conditions?
Patient surveys about quality of life, alcohol use and access to care, as well as biological material (radiology results, blood and microbiome samples, liver tissue and other data) will also be collected throughout the course of the study and stored in a shared biorepository. With patient permission, other scientists can use the samples for future research on ELT and beyond, including studies of alcohol-associated hepatitis, alcohol use disorder and liver health.
About this research
In addition to Lee and Terrault, Wendy Mack, Jennifer Dodge, Aaron Ahearn and Myles Cockburn are collaborators on the project. Chanita Hughes-Halbert is a consultant.
This work is supported by the National Institutes of Health [NIH R01AA030960].