Closing the Treatment Gap for Alcohol-Associated Liver Disease
Drinking too much—whether on a single occasion or over many years—can take a serious toll on an individual’s health. Clinicians across the health care spectrum can play important roles in preventing and treating the harmful effects of alcohol. This role is particularly important among providers who manage patients with liver diseases.
Alcohol-associated liver disease (ALD) represents a spectrum of liver conditions, including steatosis, alcohol-associated hepatitis (AH), and cirrhosis. Alcohol misuse accounts for nearly half of liver disease deaths each year, and ALD is the most common alcohol-related cause of death. ALD-related deaths increased 22.4% between 2019 and 2020, and research suggests that mortality rates are increasing faster among women and among young adults ages 25–34 than in other groups.
“We’ve known for a long time that the liver is one of the principal sites of alcohol-related harm and disease,” said National Institute on Alcohol Abuse and Alcoholism (NIAAA) Director George F. Koob, Ph.D. “Recent findings highlight the need for a paradigm shift in caring for patients with ALD.”
A growing body of evidence indicates that integrating treatment of ALD with treatment of alcohol use disorder (AUD) can improve patient outcomes. For example, a 2020 study examined the rate of hospital readmission among patients with AH who either received outpatient or residential addiction treatment or participated in a mutual-support group shortly after hospital discharge. The researchers found the rate of 30-day hospital readmission was two to three times lower than among those who did not receive such treatment. These early treatments had even greater effects on the rates of alcohol relapse in the 30 days after hospital discharge and were associated with an 80% lower risk of long-term mortality.
In a recent commentary in JAMA Network Open, Lorenzo Leggio, M.D., Ph.D., of NIAAA and the National Institute on Drug Abuse and M. Katherine Jung, Ph.D., of NIAAA summarized the state of the science supporting a paradigm shift toward integrated treatment of AUD and ALD:
- Treating AUD with medications reduces the chances of ALD and the progression of existing ALD.
- However, most patients with ALD do not receive any form of AUD therapy.
- Work is needed to develop and study health care models that integrate ALD treatment with treatment for AUD.
Need for Clinical Trials
Although research shows promise for improving patient outcomes, integrated AUD and ALD treatment has not been tested extensively through clinical trials. To address this gap, NIAAA is working with specialists in liver disease, AUD, clinical trial design, and statistics, as well as with the U.S. Food and Drug Administration (FDA) and industry, to lay the groundwork for clinical trials in this area. In July 2022, NIAAA sponsored a workshop, Clinical Trial Design for Integrated Care for Patients with AUD and ALD, to explore the design of the next generation of clinical trials to evaluate the impact of active treatment of alcohol misuse on outcomes for patients with ALD.
“We know from observational studies in patients with ALD that treatment of the underlying AUD improves clinical outcomes among this patient population both in term of severity and mortality,” said Svetlana Radaeva, Ph.D., of NIAAA, who organized the recent workshop. “Now we need to find the best ways to accomplish that goal.”
Ongoing Research Programs
Clinical trials for integrating ALD and AUD treatment will complement NIAAA’s established and ongoing research programs to close the ALD treatment gap:
- Alcohol-associated Hepatitis Network (AlcHepNet): A network of translational and clinical studies testing potential therapies, and identifying risk factors, for the onset and progression of severe AH. Research conducted through AlcHepNet is helping to pave the way for integrated treatment of ALD and AUD.
- Liver Cirrhosis Network: An initiative established by the National Institute of Diabetes and Digestive and Kidney Diseases and co-funded by NIAAA and the National Cancer Institute to better understand the natural history of liver cirrhosis and evaluate the use of statins in cirrhosis treatment.
- Medications Development Programs: Cooperative Agreement and Small Business Innovation Research (SBIR) initiatives to advance promising compounds through the drug development pipeline for the treatment of alcohol-associated organ damage and AUD.
Early Liver Transplant for Alcohol-Associated Liver Disease?
ALD is now the most common indication for liver transplantation in the United States. Many U.S. transplant centers, however, require six months of alcohol abstinence before an individual with ALD can receive a liver transplant. The rationale for this waiting period is based in part on the belief that a significant period of abstinence might allow a person’s ALD to stabilize, thereby obviating the need for transplantation. Stigma against people with alcohol-related problems may also play a role. This waiting period presents a particular challenge for patients with severe AH—a condition with a very high mortality rate in the first three to six months after diagnosis.
An emerging body of evidence suggests that patients who receive a liver transplant without the six-month waiting period (called early liver transplantation) have similar survival outcomes and alcohol relapse rates as patients who receive a transplant after the six-month waiting period. To stimulate research in this area, NIAAA has issued a request for applications (RFA) titled “Early Liver Transplantation Cohort Study for Alcohol-associated Liver Diseases.” The RFA encourages collaborative, multidisciplinary research on the factors that influence the selection, management, and long-term outcomes of patients who receive early liver transplantation.
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