Alcoholic Liver Disease: Pathogenesis and New Therapeutic Targets

By B. Gao, R. Bataller. Gastroenterology, 2011

1,858 citations recorded by the source corpus.

Alcoholic liver disease (ALD) is a major cause of chronic liver disease worldwide and can lead to fibrosis and cirrhosis. The latest surveillance report published by the National Institute on Alcohol Abuse and Alcoholism showed that liver cirrhosis was the 12th leading cause of death in the United States, with a total of 29,925 deaths in 2007, 48% of which were alcohol related. The spectrum of ALD includes simple steatosis, alcoholic hepatitis, fibrosis, cirrhosis, and superimposed hepatocellular carcinoma. Early work on the pathogenesis of the disease focused on ethanol metabolism–associated oxidative stress and glutathione depletion, abnormal methionine metabolism, malnutrition, and production of endotoxins that activate Kupffer cells. We review findings from recent studies that have characterized specific intracellular signaling pathways, transcriptional factors, aspects of innate immunity, chemokines, epigenetic features, microRNAs, and stem cells that are associated with ALD, improving our understanding of its pathogenesis. Despite this progress, no targeted therapies are available. The cornerstone of treatment for alcoholic hepatitis remains as it was 40 years ago: abstinence, nutritional support, and corticosteroids. There is an urgent need to develop new pathophysiology-oriented therapies. Recent translational studies of human samples and animal models have identified promising therapeutic targets.

Subfields: Endocrinology, Diabetes and Metabolism, Epidemiology, Pathology and Forensic Medicine

View Paper: https://www.semanticscholar.org/paper/6078c08d7fee445b11841d0261c6f9203055f0b8

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Citations in the corpus

The relationship between different dimensions of alcohol use and the burden of disease—an update (2017, background): “The pathogenesis of specific forms of alcoholic liver disease can be summarized as follows [278,279].”
Bile Acid Signaling in Metabolic Disease and Drug Therapy (2014, background): “Chronic alcohol consumption is known to alter lipid metabolism by stimulating lipogenesis and inhibiting fatty acid oxidation to contribute to alcoholic fatty liver disease (Gao and Bataller, 2011).”
Hepatic Inflammation and Fibrosis: Functional Links and Key Pathways (2015, background): “Alcoholmediated hepatocyte injury, through generation of acetaldehyde and ROS, increases the production of ROS, TNF-a, IL-1b, TGF-b, and CCL2 in the liver, predominantly through macrophages.(54,98) In part, increased inflammation in ALD is mediated by increased translocation of intestinal bacterial ”
The Role of Oxidative Stress and Antioxidants in Liver Diseases (2015, background): “With better understanding of the mechanism that regulates the initiation and advancement of ALD, antioxidant therapy could be developed as directed therapy to prevent or treat ALD [32,37,73,74].”
Liver fibrosis: Pathophysiology, pathogenetic targets and clinical issues. (2019, background): “Chronic hepatocellular injury and death is intimately related to oxidative ethanol metabolism by alcohol dehydrogenase and, particularly, the ethanol-inducible CYP2E1 cytochrome P450 isoform, leading to acetaldehyde, increased ROS generation and oxidative stress-mediated injury (exacerbated by iron ”