Beyond hereditary hemochromatosis: new insights into the relationship between iron overload and chronic liver diseases.
Following the model of hereditary hemochromatosis, the possible role of iron overload as a cofactor for disease progression in acquired liver diseases has been investigated with controversial results. In recent years, progress has been made in understanding the regulation of iron metabolism, thereby allowing the evaluation of the mechanisms linking liver diseases to excessive iron accumulation. Indeed, deregulation of the transcription of hepcidin, emerging as the master regulator of systemic iron metabolism, has been implicated in the pathogenesis of hepatic iron overload in chronic liver diseases. Whatever the cause, hepatocellular iron deposition promotes liver fibrogenesis, while an emerging possible aggravating factor is represented by the strong link between iron stores and insulin resistance, a recently recognized risk factor for the progression of liver diseases. Overall, these pathogenic mechanisms, together with the known proliferative and mutagenic effect of excess iron, converge in determining an increased susceptibility to hepatocellular carcinoma. Finally, an association between serum ferritin levels and mortality in patients with end-stage liver disease has recently been reported. Prospective, randomized studies are required to evaluate whether iron depletion may reduce fibrosis progression, hepatocellular carcinoma development, and eventually mortality in patients with chronic liver diseases.
Fargion
Silvia
S
The Department of Internal Medicine, Università degli Studi, Fondazione IRCCS Ospedale Maggiore Policlinico Ca' Granda IRCCS, Milan, Italy. silvia.fargion@unimi.it
Valenti
Luca
L
Fracanzani
Anna Ludovica
AL
D000900:Anti-Bacterial Agents / Q000378:metabolism; D023181:Antimicrobial Cationic Peptides / Q000378:metabolism; D015415:Biomarkers / Q000097:blood; D006528:Carcinoma, Hepatocellular / Q000209:etiology; D002908:Chronic Disease; D018450:Disease Progression; D005293:Ferritins / Q000097:blood; D006432:Hemochromatosis / Q000097:blood / Q000150:complications / Q000378:metabolism*; D022781:Hepatocytes / Q000378:metabolism; D064451:Hepcidins; D006801:Humans; D007333:Insulin Resistance; D007501:Iron / Q000378:metabolism*; D019190:Iron Overload / Q000378:metabolism*; D008107:Liver Diseases / Q000209:etiology / Q000378:metabolism*; D012307:Risk Factors
D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides; D015415:Biomarkers; C578702:HAMP protein, human; D064451:Hepcidins; D005293:Ferritins; D007501:Iron