Iron as a co-morbid factor in nonhemochromatotic liver disease

• Published in: Alcohol (Fayetteville, N.Y.) Vol. 30; no. 2; pp. 137 - 144
• Main Authors: Bonkovsky, Herbert L., Lambrecht, Richard W., Shan, Ying
• Format: Journal Article Conference Proceeding
• Language: English
• Published: New York, NY Elsevier Inc 01.06.2003; Elsevier Science; Elsevier Limited
• Subjects: Alcohol; Biological and medical sciences; Cirrhosis; Disease; End-stage liver disease; Fatty Liver - etiology; Fatty Liver - genetics; Gastroenterology. Liver. Pancreas. Abdomen; Hemochromatosis Protein; Hepatitis; Hepatitis C, Chronic - genetics; HFE gene; Histocompatibility Antigens Class I - genetics; Humans; Iron; Iron - adverse effects; Iron - metabolism; Iron Overload - complications; Liver - metabolism; Liver cirrhosis; Liver Diseases - etiology; Liver Diseases, Alcoholic - genetics; Liver. Biliary tract. Portal circulation. Exocrine pancreas; Medical sciences; Membrane Proteins - genetics; Mutation; Nonalcoholic fatty liver disease; Nonalcoholic steatohepatitis; Other diseases. Semiology; Porphyria cutanea tarda; Porphyria Cutanea Tarda - etiology; Porphyria Cutanea Tarda - genetics; Portasystemic Shunt, Surgical; Portosystemic shunt; Risk Factors; Rodents; Australia; Cirrhosis; Hepatitis; Portosystemic shunt; Nonalcoholic steatohepatitis; HFE gene; Porphyria cutanea tarda; End-stage liver disease; Alcohol; Iron; Nonalcoholic fatty liver disease; Human; Oxidative stress; Hepatic disease; Infection; Viral hepatitis; Viral disease; Risk factor; Fibrosis; Digestive diseases; Mutation
• ISSN: 0741-8329; 1873-6823
• DOI: 10.1016/S0741-8329(03)00127-7

Heavy iron overload, in both primary and secondary hemochromatosis, may cause fibrosis of parenchymal organs, especially the liver. The toxicity of iron is believed to involve increased oxidative stress, with iron-catalyzed production of reactive oxygen species causing oxidative damage to lipids, proteins, and nucleic acids. Lesser degrees of hepatic iron deposition are also associated with, and seem to be risk factors for, certain nonhemochromatotic liver diseases. Porphyria cutanea tarda is associated with hepatic iron overload and responds to iron-reduction therapy. Results of recent studies have demonstrated high prevalences (about 60%–80%) of HFE gene mutations in patients with porphyria cutanea tarda. Chronic hepatitis C is another risk factor for porphyria cutanea tarda. Other recent evidence indicates that the prevalence of HFE gene mutations is increased in chronic viral hepatitis and that patients with chronic hepatitis C harboring especially the C282Y mutation are more likely to suffer from advanced hepatic fibrosis or cirrhosis and to do so at younger ages. A role for modest iron overload in increasing severity of alcohol-induced liver disease has been well established from results of experimental studies. However, it is currently unresolved whether mild-to-moderate hepatic iron deposition or heterozygosity for the C282Y mutation plays a role in human alcoholic liver disease or in nonalcoholic fatty liver disease or nonalcoholic steatohepatitis. There is persuasive evidence that iron reduction decreases insulin resistance, and it likely also decreases oxidative stress, two key pathogenic features of nonalcoholic fatty liver disease/nonalcoholic steatohepatitis. Iron loading has also been described after portosystemic shunts and in end-stage liver disease.