NIH-funded Study on Early Liver Transplantation in Alcohol-associated Liver Disease Aims to Reveal Care Disparities

The National Institutes of Health has selected University of Miami Miller School of Medicine and the Miami Transplant Institute (MTI), a collaborative program with UHealth/Jackson, to help lead a national study looking at early liver transplantation access, referral, selection and  care processes for alcohol-associated liver disease.

The Miller School team, along with UT-Southwestern, Columbia University and University of Michigan, make up one of two consortia selected. Each site will receive $2.7 million for the seven-year study.

A primary goal of the study is to characterize and develop risk prediction models for transplant-free survival among those with limited access to liver transplant. The models would help target those in greatest need of early liver transplant (defined as less than six months sobriety) referral and listing, according to co-principal investigator David Goldberg, M.D., associate professor of medicine, Division of Digestive Health and Liver Diseases at the Miller School.

Other study aims, according to Dr. Goldberg, are to evaluate barriers and facilitators to referral for early liver transplant in alcohol-associated liver disease; evaluate biopsychosocial factors and develop risk models predictive of outcomes at key timepoints in early liver transplant for this liver disease type; define stakeholder perceptions and preferences for selection and outcomes in early liver transplant for alcohol-associated liver disease; and evaluate how integrated care processes influence outcomes in early liver transplant for the disease.

The Miller School and MTI are ideally positioned for this research, he said.

“The University of Miami/MTI has one of the most diverse patient populations among all transplant centers. This will allow us to evaluate the question of early liver transplantation for alcohol-associated liver disease in patients from diverse cultural backgrounds, where there are different beliefs and stigmas associated with alcohol use,” Dr. Goldberg said. “And because complications of alcohol-associated liver disease may differ across different populations, we will be able to address that in our population.”

Evaluating Patients for Liver Transplant

MTI, one of the largest liver transplant programs in the country, has a large number of transplants for early liver transplantation for alcohol-associated liver disease.

The process of evaluating patients for early liver transplantation across transplant centers varies, and there is no established right or wrong way to do it, according to Dr. Goldberg.

“We evaluate each patient individually, without hard cut points for inclusion like other centers. This grant will allow us to compare and evaluate processes and outcomes in our population compared to others,” Dr. Goldberg said.

Importantly, the study will offer a better understanding of which patients are the best candidates for early liver transplant.

“In addition, because the definition of transplant ‘success’ varies across stakeholders, we will be conducting qualitative research among patients, providers, transplant staff and donor families to help define what metrics should be used to define success in transplanting patients with alcohol-associated liver disease,” he said.

Collaborative Multidisciplinary Team

The collaborative team on the grant is multidisciplinary and runs the spectrum from junior to senior investigators, including three junior investigators.

“This allows us to train and mentor junior faculty in research while ensuring research continuity for this seven-year grant,” Dr. Goldberg said.

One of the junior investigators and grant co-principal investigator Natasha Schaefer Solle, Ph.D., R.N., research assistant professor at the Miller School, is also a consortium steering committee member and lead qualitative researcher on the project.

“Our Miami site will serve as the lead for the Qualitative and Mixed Methods Core, working with members from across the INTEGRATE collaborative to ensure the implementation and analysis of the qualitative data is completed successfully,” Dr. Solle said. “Working with the Behavioral and Community-based Research Shared Resource, our Miami team will be responsible for developing culturally and linguistically competent study materials, specifically for the Hispanic and Caribbean patients.”

The research involves transplant patients, patients hospitalized at Jackson and referring community gastrointestinal doctors.

Debate over Allocating Scarce Organs

Junior investigator and grant investigator Eric Martin, M.D., part of the liver transplant team at MTI, said this research will help to shed light on a difficult topic.

Allocating scarce organs to patients with alcohol-associated liver disease remains an ongoing debate, with renewed interest because of the increasing number of publications on the benefits of early liver transplantation in severe alcohol-associated hepatitis — the occurrence of which more than doubled during the COVID-19 global pandemic, according to Dr. Martin, who also is medical director of the Living Donor Liver Transplant program at the Miller School.

“Despite the fact that alcohol-associated liver disease is now the most common indication for liver transplantation in the United States, there remains significant variation in referral practices throughout the U.S. due in large part to the negative stigma inherent in alcohol-associated liver disease,” Dr. Martin said. “This collaborative study provides a tremendous opportunity to help destigmatize alcohol-associated liver disease and standardize referral and selection practices utilizing objective methods, rather than scrutinizing subjective patient profiles on a case-by-case basis.”

Dr. Martin said he hopes this collaborative study will help overcome the arbitrary “six-month rule” that many providers still use as a marker to achieve before consideration for liver transplantation.

“Basing a candidate’s eligibility for a lifesaving procedure such as early liver transplantation on a fixed period of sobriety alone may penalize a few select patients with unnecessary delays in referrals and listing due to recent drinking who are otherwise at low risk for relapse, because many are unlikely to survive the requisite six months,” Dr. Martin said. “This is unfortunate, as the use of the so-called six-month rule shows an overall poor understanding of alcohol use disorder, which is a very complex mental behavior disorder.

“This much-needed study will not so much challenge the public opinion regarding the negative stigma of alcohol-associated liver disease, but ultimately help identify patient profiles that are associated with the best transplant-related outcomes, which will go a long way in standardizing our care for patients with alcohol-associated liver disease,” he said.

Other investigators from the Miller School and MTI include Daniel Maass, M.D.; Olveen Carrasquillo, M.D., M.P.H.; and Paul Martin, M.D.  

Tags: Dr. David Goldberg, liver disease, liver transplant, miami transplant institute, NIH funding, USNWR Gastro