UofL researchers have discovered four significant alterations in proteins involved in alcohol-associated hepatitis and alcohol-associated cirrhosis, common forms of alcohol-associated liver disease that have poor prognosis and for which standard treatments offer limited effectiveness. Identification of these changes may present opportunities for new treatments for these conditions.

Alcohol-associated liver disease (ALD) contributes to more than 500,000 deaths worldwide annually. Two types of ALD, alcohol-associated hepatitis (AH) and alcohol-associated cirrhosis (AC), have a particularly poor prognosis and few treatment options.

The researchers analyzed liver tissues and liver biopsies from AH and AC patients and observed four significant changes in the proteins involved in biological processes associated with liver disease, including liver fibrosis or scar tissue, low albumin levels, white blood cell function and production of cardiolipin. These alterations may be adapted to serve as biomarkers to diagnose these conditions, assess the level of severity of AH and used as targets to develop new treatments.

“Many patients with ALD are unaware of the severity of their condition, and there are very few medical treatment options available,” said Irina A. Kirpich, associate professor of medicine at UofL, who led the study along with Jon Jacobs of Pacific Northwest National Laboratory in Richland, Washington. “This problem has intensified over time and the COVID-19 epidemic has exacerbated alcohol-related hospitalizations. There is a real necessity for the identification and development of biomarkers and treatments.”

Results of the study, which involved UofL researchers Kirpich, Professor Craig McClain, postdoctoral associate Josiah Hardesty and researcher Dennis Warner, were published in the July issue of the The American Journal of Pathology.

“This one-of-a-kind study and its novel proteomic dataset will provide a roadmap for the development of novel biomarkers and therapies for AH and AC,” Kirpich said. “We are optimistic that findings from this study will be utilized by investigators in the field for years to come and could help enhance current treatment strategies to improve patient outcomes and open the door to new paradigms and ideas to improve patient care.”