Hemochromatosis: update on diagnosis and patient management starting from the EASL CPG

Please use this link: https://uke-de.zoom-x.de/j/67934597948?pwd=0JY3b8QbO0wNRMjzqHu6ntT80ach9j.1 

Speakers: 

Heinz Zoller, Medical University of Innsbruck-Department of Medicine I (Hemochromatosis EASL CPG chair)

Elena Corradini, Azienda Ospedaliero-Universitaria di Modena, Università degli Studi di Modena e Reggio Emilia, Italy (Hemochromatosis EASL CPG pannelist)

Chair:

Antonello Pietrangelo, Azienda Ospedaliero-Universitaria di Modena

Agenda:

Hemochromatosis (HC) is the most common inherited disorder among Caucasians and, if left untreated, can become a systemic and life-threatening condition. Homozygosity for the p.Cys282Tyr variant in the HFE gene accounts for about 80% of HC cases in people of European descent. For non-Europeans, or Europeans who are not p.Cys282Tyr homozygotes, HC arises from rarer mutations in either the HFE gene or non-HFE genes, such as Transferrin Receptor 2 (TfR2), Ferroportin-1 (FPN-1), or in younger patients, hemojuvelin (HJV) and hepcidin (HAMP), making HC a genetically heterogeneous disease.

The penetrance of p.Cys282Tyr homozygosity is generally low, and the clinical expression of HFE-related HC varies, influenced by factors like age, sex, and other genetic or environmental modifiers. The non-HFE forms of HC tend to be more severe. Early or mild forms of HC may present with non-specific symptoms such as elevated ferritin levels, liver enzyme abnormalities, hepatomegaly, joint pain, and fatigue. If untreated, HC can progress to liver fibrosis, cirrhosis, or liver cancer, particularly hepatocellular carcinoma. UK Biobank studies have recently confirmed that p.Cys282Tyr homozygosity is a risk factor for liver cancer and increased mortality. Severe or early-onset forms of HC can also lead to complications like diabetes, hypogonadotropic hypogonadism, hypothyroidism, and heart failure.

The clinical manifestations of HC depend on the stage of the disease, the extent of iron overload, and organ damage. Therefore, proper staging—evaluating iron load and liver involvement—is crucial for managing the disease. The 2022 EASL guidelines on HC emphasize genetic insights and the use of MRI as a non-invasive diagnostic tool. Liver biopsy is now mainly reserved for cases involving other liver diseases or when advanced fibrosis or cirrhosis needs confirmation.

Accurate diagnosis, timely treatment, and careful follow-up are key to preventing complications in HC patients. The panel will discuss these points, starting from the EASL guidelines released in 2022, focusing on disease manifestations, diagnosis and patient management, and including the more extensive use of genetic tests and MRI for disease diagnosis and non-invasive body iron assessment.

Short bios:

Heinz Zoller is a Professor of Hepatoloy at the Medical University of Innsbruck, Austria. As physician scientist he is senior consultant at the University Hospital, where he cares for patients with liver diseases and has a particular focus on pre- and post-livertransplant patients. Heinz Zoller studied and trained in Austria and Cambridge, UK before he was appointed in Innsbruck. His main research interest is iron metabolism which led to numerous publications on hemochromatosis and rare iron disorders. The EASL clinical practice guidelines on hemochromatosis and the Biorion update on hemochromatosis classification and nomenclature are among his recent contributions to the field, where he is aiming to translate basic science into improved patient care. 

Elena Corradini is an Associate Professor of Internal Medicine at the University of Modena and Reggio Emilia, Italy. She is an internal medicine specialist and practices inpatient and outpatient clinics at the Internal Medicine Unit and the Centre for Hemochromatosis and Hereditary Liver Diseases at the University Hospital of Modena, where she is in charge of the Hemochromatosis and Hereditary Liver Diseases Outpatient Clinic and the Laboratory of Molecular Genetics. She is also a member of the Laboratory of Iron Metabolism team led by Prof. Antonello Pietrangelo. Her basic and clinical research activities focus primarily on iron metabolism and iron-related disorders, including genetic and acquired liver diseases with altered iron homeostasis, as well as complex internal medicine diseases. She was also a panel member of the 2022 EASL Clinical Practice Guidelines on Haemochromatosis.

Prof. Antonello Pietrangelo, M.D., Ph.D., is the Director of the Internal Medicine Unit and the Center for Hemochromatosis and Rare Liver Diseases at the University Hospital of Modena, Italy. He has dedicated his professional and scientific career to the study of liver diseases, particularly focusing on rare liver disorders. Prof. Pietrangelo is the founder and first president of the International Society for the Study of Iron in Biology and Medicine (BioIron). He has also served as a member of the Scientific Committee and as chair of the Ethics Committee of the European Association for the Study of the Liver (EASL). Currently, he is the national coordinator of the Spoke unit for “Genetic Diseases” under the National Center for Gene Therapy and Drugs Based on RNA Technology, funded by the EU. He coordinates the ERN RARE-LIVER working group on Hemochromatosis and Rare Hepatic Iron-Loading Diseases (HILD).