Iron and the Liver

I was delighted to be asked by Dr. Paul Berk to be the Guest Editor of this issue of Seminars in Liver Disease on “Iron and the Liver.” In 1984, very early in my academic career, I coauthored a review for Seminars in Liver Disease on the “Role of the Liver in Normal Iron Metabolism,” which was the first time the topic of iron and the liver was fully reviewed in Seminars. Then in 1996, Dr. Anthony Tavill and I were guest editors for an issue of Seminars entitled “Metals and Free-Radical-Induced Liver Injury.” A lot has happened since then with the discovery of HFE in 1996, and with the subsequent explosion of new molecular, genetic, and cell biologic information that has come since that time. We are now much smarter about hepatic iron metabolism and the various iron-overload disorders. For example, we now know that there are several genetic abnormalities that can cause hereditary hemochromatosis. Nonetheless, it is recognized that the vast majority of patients with inherited iron overload are homozygous for the C282Y mutation in HFE. Conversely, not all patients who are C282Y homozygotes develop evidence of phenotypic expression (i.e., iron overload).

For the current issue of Seminars, we have selected an “all-star” field of authors. Dr. Lawrie Powell, from Brisbane, is arguably the “Dean” of hemochromatosis worldwide and he and Dr. O'Neil have beautifully summarized the clinical aspects of hemochromatosis to start the issue. Dr. Elizabeth Brunt has prepared a cogent review of the pathological changes that are seen in patients with all forms of iron overload. I asked Dr. John Olynyk and colleagues to summarize the issue of screening for HFE and iron overload since he had done seminal work in this area evaluating and analyzing the Busselton community several years ago. Our own group, led by Drs. Fleming and Sly, has provided a review of the proposed pathophysiological mechanisms that are currently most favored in understanding the pathophysiology of HFE-linked disease. New information about hepcidin has provided a unifying hypothesis, but many aspects of hepcidin regulation still need to be worked out. Drs. Gregory Anderson and David Frazer, also of Brisbane, have provided an outstanding review of the movement of iron in liver cells, and their colleagues at the Queensland Institute of Medical Research, Drs. Grant Ramm and Richard Ruddell have nicely summarized all pertinent aspects of liver toxicity related to iron overload. Dr. Antonello Pietrangelo has been at the forefront of many important discoveries in clinical and laboratory-based iron metabolism. I asked him to write about non-HFE-linked hemochromatosis and he has delivered a superb review. Finally, Dr. Herbert Bonkovsky has written on numerous occasions about the role of iron in other liver diseases, such as hepatitis C and fatty liver disease, and as is well known, Dr. Bonkovsky is an expert in the porphyrias. Along with Dr. Vamsee Alla, he has turned in one of his characteristic thorough articles on this important topic.

The collected authors are all experts in their fields and the articles that they have provided will be studied by “ferrophiles” from around the world for quite some time.