Iron is essential for cellular functions, but in excessive amounts it is toxic to cells. The harmful effects are related to increased oxidative stress and production of reactive oxygen species causing oxidative damage to lipids, proteins, and nucleic acids. Heavy iron overload as occurs in primary and secondary hemochromatosis can cause fibrosis of various parenchymal organs such as the liver, heart, and pancreas. 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. 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. In this article we review selected nonhemochromatotic disorders in which iron can play an important comorbid role.

Although the cause of autoimmune hepatitis (AIH) is unknown, drugs are believed to be potential triggers in some patients. In isolated case reports, statins have been considered such triggers. Here we describe 3 patients in whom it is probable that statins initiated the development of AIH. Two men (aged 47 and 51) and one woman (aged 57) developed AIH after the initiation of statin therapy. They developed positive titers of antinuclear antibodies, antismooth muscle antibodies (1/40 to 1/160), and hypergammaglobulinemia. Features of all 3 patients met the criteria for AIH according to the International Autoimmune Hepatitis Panel. Liver biopsies in all 3 showed varying stages of fibrosis and plasma cell infiltration, compatible with AIH. The woman developed hepatitis due to statins on 2 separate occasions: the first in 1999, due to simvastatin, and the second in 2001 to 2002, due to atorvastatin, which was severe and persisted even after discontinuing medication. Similarly, in the 2 other cases, exposure to statins preceded development of AIH, which persisted despite discontinuing medications. All 3 patients responded well to prednisone and azathioprine or mycophenolate therapy. 3 similar previously reported cases are reviewed. We conclude that the 3 cases reported here and 3 similar previously reported cases, indicate that severe, ongoing AIH on rare occasions can be triggered by statins.