Alcohol-associated liver disease: A review on its pathophysiology, diagnosis and drug therapy. (2021)

• Record Type: Journal Article
• Authors: Subramaniyan, Vetriselvan; Chakravarthi, Srikumar; Jegasothy, Ravindran; Seng, Wu Yuan; Fuloria, Neeraj Kumar; Fuloria, Shivkanya; Hazarika, Iswar; Das, Anju
• Is Part Of: Toxicology reports. Volume 8(2021)
• Page Start: 376
• Page End: 385
• Publication Date: 2021
• Subjects: ALD alcohol associated liver disease -- ALT alanine aminotransferase -- AST aspartate aminotransferase -- CD14 cluster of differentiation14 -- CHD congenital heart disease -- ECM extracellualr matrix -- FASD fetal alcohol spectrum disorders -- FDA food and drug administration -- GGTP gamma-glutamyl transpeptidase -- GSH Glutathione -- H2O2 hydrogen peroxide -- HCV chronic hepatitis C -- HSC hepatic stellate cells -- IGR intrauterine growth retardation -- IL interleukin -- JECH Japan Environment and Children's Study -- MDF maddrey's discriminant function -- NA nutritional assessment -- NAC N-acetylcysteine -- NADPH Nicotinamide adenine dinucleotide phosphate -- OLT Orthotopic liver transplantation -- ROS reactive oxygen species -- TLR4 toll-like receptor 4 -- TNF Tumor necrosis factor; Alcohol -- Liver pathogenesis -- Pregnancy -- Immune modulation -- Targeted therapy; Toxicology -- Periodicals; Clinical toxicology -- Periodicals; Drug-Related Side Effects and Adverse Reactions; Hazardous Substances; Poisoning; Toxicology; Electronic journals; Periodicals; Periodicals; 571.9505
• DOI: 10.1016/j.toxrep.2021.02.010
• Languages: English
• ISSNs: 2214-7500

Abstract

Highlights: Chronic intake of alcohol initiates a pathogenic process that involves the production of protein-aldehyde adducts, and release of cytokines. Involved gene polymorphisms may include alcohol dehydrogenase, cytochrome P4502E1, and those associated with alcoholism. Alcohol ingestion could be correlated to the risk of preterm births, there is no exact dose-response relationship. Oral drugs of pentoxifylline have reduced the severity of steatohepatitis in alcohol-use patients. Abstract: One of the global burdens of health care is an alcohol-associated liver disease (ALD) and liver-related death which is caused due to acute or chronic consumption of alcohol. Chronic consumption of alcohol damage the normal defense mechanism of the liver and likely to disturb the gut barrier system, mucosal immune cells, which leads to decreased nutrient absorption. Therapy of ALD depends upon the spectrum of liver injury that causes fatty liver, hepatitis, and cirrhosis. The foundation of therapy starts with abstinence from alcohol. Corticosteroids are used for the treatment of ALD but due to poor acceptance, continuing mortality, and identification of tumor necrosis factor-alpha as an integral component in pathogenesis, recent studies focus on pentoxifylline and, antitumor necrosis factor antibody to neutralize cytokines in the therapy of severe alcoholic hepatitis. Antioxidants also play a significant role in the treatment but till today there is no universally accepted therapy available for any stage of ALD. The treatment aspects need to restore the gut functions and require nutrient-based treatments to regulate the functions of the gut system and prevent liver injury. The vital action of saturated fatty acids greatly controls the gut barrier. Overall, this review mainly focuses on the mechanism of alcohol-induced metabolic dysfunction, contribution to liver pathogenesis, the effect of pregnancy, and targeted therapy of ALD.