INDIANAPOLIS—Researchers from Indiana University School of Medicine and the National Institutes of Health are learning more about what happens to the body when someone develops severe alcoholic hepatitis and how it could be treated in the future.
“Alcohol-associated hepatitis is the most severe form of liver injury happening in patients who drink excessively,” said Suthat Liangpunsakul, MD, MPH, a co-corresponding author of the study and professor of medicine at IU School of Medicine. “In severe cases, the short-term mortality is extremely high. One in three people will die when they develop it. But so far, not much is known about the mechanism of how all of this happens.”
In the translational study recently published in the Journal of Clinical Investigation, scientists focused on describing the patterns of neutrophils, which are a type of white blood cell, and their involvement in severe alcoholic hepatitis pathogenesis. When someone develops severe alcoholic hepatitis, their neutrophil levels increase, but it is unclear how those neutrophils can trigger inflammation or what is happening in the liver. Researchers looked at a cohort of almost 40 patients and observed two groups of inflammatory cell infiltration—one with high neutrophils, the other with low neutrophils. They completed gene sequencing to identify target genes and how they interact with the neutrophils and studied what happened to the liver when manipulating the genes in animal models.
“We are able to characterize the two distinct phenotypes based on these cells, suggesting there is a separate mechanism driving liver injury and/or failure in these patients,” Liangpunsakul said.
Currently, patients with alcoholic hepatitis are treated with steroids, but not all patients respond well to steroid. Liangpunsakul said identifying whether a patient has high or low neutrophils could help determine how well a patient will respond to steroid treatment.
“When you have low neutrophils but high T cells, steroids may work better because steroids effectively blocked the T cell-mediated inflammatory cascade. But another group of patients with high neutrophils may have a different inflammatory driven process to begin with, so if they receive steroids, we may not get a response because neutrophils poorly respond to steroid treatment,” said Bin Gao, MD, PhD, another co-corresponding author and the Chief of Laboratory of Liver Diseases at the National Institute on Alcohol Abuse and Alcoholism. “More study is needed to identify how high versus low neutrophils can impact responses to treatment.”
The study was funded in part by the National Institute on Alcohol Abuse and Alcoholism. The lead author is Jing Ma, PhD, a post-doctoral fellow currently at IU School of Medicine, and was a PhD student at the National Institute of Alcohol Abuse and Alcoholism.
IU School of Medicine is the largest medical school in the U.S. and is annually ranked among the top medical schools in the nation by U.S. News & World Report. The school offers high-quality medical education, access to leading medical research and rich campus life in nine Indiana cities, including rural and urban locations consistently recognized for livability.
Journal of Clinical Investigation
Distinct histopathological phenotypes of severe alcoholic hepatitis suggest different mechanisms driving liver injury and failure
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