In a groundbreaking study, research scientists from the Indiana University School of Medicine and Regenstrief Institute found that individuals with a parent who died from liver disease face more than double the risk of developing alcohol-associated hepatitis, one of the deadliest forms of alcohol-related liver disease, compared with similar heavy drinkers without that family history.
Researchers investigated the impact of parental liver disease mortality on both the development and outcomes of alcohol-associated hepatitis in adult children. In the U.S., nearly 20,000 people die from alcoholic liver disease each year, according to the National Council on Alcoholism and Drug Dependence.
Alcohol-associated hepatitis is a severe and often fatal form of alcohol-associated liver disease. Although excessive alcohol use is a key risk factor, the precise biological mechanisms that cause some heavy drinkers to develop alcohol-associated hepatitis while others do not remain unclear.
The study analyzed data from two large, multicenter cohorts, including patients with alcohol-associated hepatitis and heavy-drinkers without significant liver disease. Researchers documented that parental alcohol use disorder was common in both groups, but it was a parent’s death due to liver disease – not simply a history of alcohol use – that was associated with increased risk of alcohol-associated hepatitis.
The study’s authors emphasize that identifying individuals with a family history of liver disease mortality could enable earlier intervention and counseling to reduce alcohol consumption, potentially preventing the onset of alcohol-associated hepatitis.
“Alcohol-associated hepatitis is a life-threatening condition with high short-term mortality. So far there is no effective treatment that is approved by the FDA,” said first author, IU School of Medicine Professor and Regenstrief Research Scientist Wanzhu Tu, PhD. “Corticosteroids could help reduce liver inflammation, but these drugs also increase the risk of infection. And many patients are ineligible for steroids. So, treatment options are limited.
“The best way to reduce the mortality and morbidity of alcohol-associated hepatitis is to prevent it from occurring in the first place, which is why reducing alcohol consumption has always been a primary focus,” said Dr. Tu, who led the study. “For prevention, it’s especially important to identify people who are at higher risk. That’s why this study is important. When a patient reports that a parent died of liver disease, that’s not just background information — it’s a red flag. It may indicate a genetic or familial susceptibility, and that’s exactly what our data show.”
The researchers also found that patients who have been diagnosed with alcohol-associated hepatitis, who had a parent die from liver disease, are more likely to die themselves within 90 days of diagnosis.
“A parent’s death from liver disease is a clear and measurable risk marker,” said Samer Gawrieh, M.D., a professor at the IU School of Medicine and the corresponding author of the paper. “Recognizing this can help clinicians identify those at higher risk for alcohol-associated hepatitis and guide preventive strategies. For those already diagnosed, discussing family history can be a powerful tool to encourage alcohol abstinence and improve outcomes.”
A call for further research
The research also highlights a pressing need to further investigate genetic and epigenetic factors that may underlie this familial risk, beyond shared environmental influences or drinking patterns.
“This could be due to inherited genetic susceptibility, environmental stressors or a combination of both,” said Dr. Gawrieh. “Either way, it’s a critical piece in understanding who is most vulnerable to the devastating consequences of alcohol misuse.”
“Parental liver disease mortality is associated with unfavorable outcomes in patients with alcohol-associated hepatitis,” is published in the academic journal Hepatology Communications.
The study was funded by the National Institutes of Health (NIH) through the Alcoholic Hepatitis Network (AlcHepNet) and the Translational Research Evolving Alcoholic Hepatitis Treatment (TREAT) consortium.
Authors and their affiliations, as listed in the publication, are:
Wanzhu Tu1, Samer Gawrieh1, Lauren Nephew1, Craig McClain2, Qing Tang1, Srinivasan Dasarathy3, Vatsalya Vatsalya2, Douglas A Simonetto4, Carla Kettler1, Gyongyi Szabo5, Bruce Barton6, Yunpeng Yu1, Patrick S Kamath4, Arun J Sanyal7, Laura Nagy3, Mack C Mitchell8, Suthat Liangpunsakul1, Vijay H Shah4, Naga Chalasani1, Ramon Bataller9; AlcHepNet Investigators
Affiliations
1Department of Medicine, and Department of Biostatistics and Health Data Science, Indiana University School of Medicine, Indianapolis, Indiana, USA.
2Department of Medicine, University of Louisville, Louisville, Kentucky, USA.
3Department of Gastroenterology, Hepatology and Nutrition, Cleveland Clinic, Cleveland, Ohio, USA.
4Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota, USA.
5Department of Medicine, Harvard University, Boston, Massachusetts, USA.
6Department of Population and Quantitative Health Sciences, University of Massachusetts, Worcester, Massachusetts, USA.
7Department of Internal Medicine, Virginia Commonwealth University, Richmond, Virginia, USA.
8Department of Internal Medicine, UT Southwestern Medical Center, Dallas, Texas, USA.
9Department of Medicine, Universitat de Barcelona, Barcelona, Spain.
Wanzhu Tu, PhD
In addition to his role as a research scientist with the Indiana University Center for Aging Research at Regenstrief Institute, Wanzhu Tu, PhD, is a professor and the vice chair in the Department of Biostatistics and Health Data Science at Indiana University School of Medicine. He is also an adjunct professor at the Indiana University Indianapolis Richard M. Fairbanks School of Public Health.
