Alcohol-Induced Hepatic Fibrosis and the Relation between Hepcidin and Liver Fibrosis

Abstract

Abstract: Alcoholic liver disease (ALD) is a worldwide health problem that may lead to development of fatty liver steatosis, hepatitis and cirrhosis. Alcohol is known to exert a harmful effect on a variety of human tissues. In particular, the liver is the major site of alcohol-induced damage because it is the direct recipient of the blood that contains elevated levels of alcohol, and it is the major organ responsible for alcohol metabolism. The damage caused by ethanol is mainly attributed to its metabolic process that results in production of acetaldehyde and reactive oxygen species (ROS) such as hydrogen peroxide, superoxide and free hydroxyl radical. These metabolites cause depletion of reduced glutathione (GSH), peroxidation of cellular membranes, oxidation of macro-molecules such as proteins and nucleic acids, and eventually lead to progressive injury of hepatocytes. Additionally, ethanol and its metabolic products enhance the production of pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6). The enhanced production of those inflammation factors; stimulated partially by oxidative stress; results in cytokine imbalance and immune disorders, leading to further hepatic damage. Thus, agents with anti-inflammatory and anti-oxidative properties might be potential candidates for protection against alcohol-induced liver disease. The metabolic functions of the alcoholic liver are seriously affected. Disorders in iron metabolism are characteristic of ALD. Abnormal levels of iron, ferritin, and transferrin were reported in ALD. Hepcidin, the principle hepatic regulator of the metabolism of iron, is decreased in ALD.