Key Events Participating in the Pathogenesis of Alcoholic Liver Disease

Abstract

Alcoholic liver disease (ALD) is a leading cause of morbidity and mortality worldwide. It ranges from fatty liver to steatohepatitis, fibrosis, cirrhosis and hepatocellular carcinoma. The most prevalent forms of ALD are alcoholic fatty liver, alcoholic hepatitis (AH) and alcoholic cirrhosis, which frequently progress as people continue drinking. ALD refers to a number of symptoms/deficits that contribute to liver injury. These include steatosis, inflammation, fibrosis and cirrhosis, which, when taken together, sequentially or simultaneously lead to significant disease progression. The pathogenesis of ALD, influenced by host and environmental factors, is currently only partially understood. To date, lipopolysaccharide (LPS) translocation from the gut to the portal blood, aging, gender, increased infiltration and activation of neutrophils and bone marrow-derived macrophages along with alcohol plus iron metabolism, with its associated increase in reactive oxygen species (ROS), are all key events contributing to the pathogenesis of ALD. This review aims to introduce the reader to the concept of alcohol-mediated liver damage and the mechanisms driving injury.

Lactobacillus plantarum prevents and mitigates alcohol‐induced disruption of colonic epithelial tight junctions, endotoxemia, and liver damage by an EGF receptor‐dependent mechanism

“…Disruption of AJCs leads to diffusion of LPS from the gut lumen into the intestinal mucosa and delivered to liver via portal veins. LPS acts as a key mediator of inflammation in the liver and forms an important trigger in the development of ALD (6). Endotoxin activates Kupffer cells by a TLR-4-dependent mechanism to release inflammatory cytokines and reactive oxygen species, which are known to play key roles in alcoholic liver damage and pathogenesis of ALD.…”

TSG-6 Inhibits Oxidative Stress and Induces M2 Polarization of Hepatic Macrophages in Mice With Alcoholic Hepatitis via Suppression of STAT3 Activation

“…We next examined the hepatic infiltration of macrophages, since activation of peripheral and infiltrating bone-marrow monocytes and macrophages plays a very important role in ALD (McClain et al, 2002;Magdaleno et al, 2017). There are two distinct types of macrophages, M1 and M2 macrophages.…”

Alcoholism, Fibroblast Growth Factor 23 and Cardiovascular Risk

“…Altered iron homeostasis in liver disease, especially among alcoholics [44], might also explain increased FGF-23 in this disease. As mentioned before, sequestered iron, via HIF, may trigger an excessive production of FGF-23 by the hepatocyte.…”