Researchers Gain New Insight Into the Development of Severe Alcohol-Associated Hepatitis
Alcohol misuse can lead to alcohol-associated hepatitis (AH), a form of liver disease with a high short-term mortality rate in severe cases. Currently, no medications have been approved by the U.S. Food and Drug Administration to treat AH, and liver transplantation is often required due to liver failure. A better understanding of how AH develops could help improve AH treatment and prevent progression to severe disease. A recent study has shown a positive correlation among neutrophilic infiltration and the model for end-stage liver disease score (MELD score, a scoring system predicting prognosis of liver disease) and serum alanine aminotransferase (ALT) levels. Researchers found a mechanism by which neutrophils—a type of white blood cell—contribute to liver injury in AH. Published in the Journal of Clinical Investigation, the study was supported by the National Institute on Alcohol Abuse and Alcoholism.
A growing body of evidence indicates that various types of cells in the body’s immune system are involved in AH, including neutrophils. When a person develops severe AH, the levels of neutrophils increase in the liver, but how these cells contribute to the development of the disease is not clear. To gain insight, the researchers examined neutrophils and other immune cells in the livers of 40 patients with severe AH. The authors showed that neutrophil-derived reactive oxygen species (ROS) promoted liver injury and inflammation in the experimental model. This suggests that neutrophil-generated ROS is one of the mechanisms that contribute to liver injury and dysfunction in severe AH in addition to many other cell types involved in severe AH pathogenesis.
More specifically, the researchers found increased expression of neutrophil cytosolic factor 1 (NCF1), a gene involved in controlling ROS. To gain insight into the mechanism of NCF1 in severe AH with high neutrophil levels, the researchers examined NCF1 in an animal model of liver injury. They found that NCF1 contributes to higher levels of ROS and thus liver inflammation/injury by inhibiting adenosine monophosphate-activated protein kinase (AMPK, a key regulator of lipid metabolism) and by inhibiting microRNA-223 (a key anti-inflammatory microRNA). MicroRNAs are non-coding RNA molecules thought to play a key role in and the regulation of gene expression.
These findings provide important insight into the mechanisms that may drive liver injury, and ultimately liver failure, in individuals with severe AH. Additional clinical and translational research is needed to more fully characterize the pathological mechanisms that contribute to severe AH and to identify novel therapeutic targets for this devastating disease.
References
Ma J, Guillot A, Yang Z, Mackowiak B, Hwang S, Park O, Peiffer BJ, Ahmadi AR, Melo L, Kusumanchi P, Huda N, Saxena R, He Y, Guan Y, Feng D, Sancho-Bru P, Zang M, Cameron AM, Bataller R, Tacke F, Sun Z, Liangpunsakul S, Gao B. Distinct histopathological phenotypes of severe alcoholic hepatitis suggest different mechanisms driving liver injury and failure. J Clin Invest. 2022;132(14):e157780. PubMed PMID: 35838051
In this Issue
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.
New Research Characterizes Alcohol Use Disorder Profiles To Predict Treatment Outcomes
Alcohol use disorder (AUD) is a heterogeneous disorder, meaning individuals with AUD differ in their clinical symptoms and in the biological and psychological factors that contribute to their disorder. A better understanding of individual differences in AUD could inform the development of tailored treatment approaches to increase treatment effectiveness. New research from the University of New Mexico, the University of Washington, and Syracuse University published in Psychology of Addictive Behaviors shows that assessing patients based on biological and psychological domains of addiction could
Heart Medication Shows Potential as Treatment for Alcohol Use Disorder
Spironolactone, a medication for heart problems and high blood pressure, may also be effective for treating alcohol use disorder (AUD), according to a new National Institutes of Health study. The study presents converging evidence from experiments in rodents, as well as electronic health data from humans, suggesting that spironolactone may play a role in reducing alcohol drinking. The research, published in Molecular Psychiatry, was led by scientists at the National Institute on Alcohol Abuse and Alcoholism (NIAAA), the National Institute on Drug Abuse (NIDA), and Yale School of Medicine in
National Conference Focuses on Health Issues Affecting Women and Girls
In October, the National Institute on Alcohol Abuse and Alcoholism (NIAAA) and the Interagency Work Group on Drinking and Drug Use in Women and Girls (IWG) hosted the 2022 National Conference on Alcohol and Other Substance Use in Women and Girls: Advances in Prevention, Treatment, and Recovery. More than 400 attendees participated in the two-day virtual conference, which featured plenary lectures by NIAAA Director George F. Koob, Ph.D., National Institute on Drug Abuse Director Nora Volkow, M.D., and National Institute of Mental Health Director Joshua Gordon, M.D., Ph.D. Valerie A. Earnshaw
Alcohol-Related Deaths Continued To Increase in 2021
The figure above shows the number of alcohol-related deaths each month in 2019, 2020, and 2021. The annual total number of deaths increased 25% between 2019 and 2020 (from 78,927 to 99,017). The annual total number increased another 10% between 2020 and 2021 (from 99,017 to 108,891).