Secondary Iron Overload and the Liver: A Comprehensive Review

Abstract

Iron overload is a condition involving excessive iron deposit in various organs, the liver being the main target organ for iron deposition and overload which are associated with significant liver morbidity and mortality. Iron overload can be categorized into primary and secondary causes. Primary iron overload, so-called hereditary hemochromatosis, is a well-recognized disease with available standard treatment recommendations. However, secondary iron overload is a more diverse disease with many unclear areas to be explored. Secondary iron overload is more prevalent than primary iron overload and occurs as a consequence of various causes which differ significantly across geographic regions. The main causes of secondary iron overload are iron-loading anemias, and chronic liver disease. The liver-related outcomes, patient outcomes, and treatment recommendations in these patients differ depending on the cause of iron overload. This review summarizes the causes, pathophysiology, liver-related outcomes, disease outcomes, and treatments of secondary iron overload.

Keywords: Cirrhosis; Hemochromatosis; Hepatocellular carcinoma; Iron overload; Thalassemia.

Fig. 1. Hepcidin-mediated regulation of iron homeostasis and pathophysiology of iron overload in various diseases.

(A) Hepcidin-mediated regulation of iron homeostasis (adapted from Brissot P, et al.6). (B) Pathophysiology of iron overload in iron-loading anemias. (C) Pathophysiology of iron overload in non-alcoholic fatty liver disease. (D) Pathophysiology of iron overload in hepatitis C virus infection, and alcoholic liver disease. DMT1, divalent metal transporter 1.

Fig. 2. Proposed algorithm of approach to patients with hyperferritinemia.

ALD, alcoholic liver disease; HBV, hepatitis B virus; HCV, hepatitis C virus; MRI, magnetic resonance imaging; NAFLD, non-alcoholic fatty liver disease.