Edouard Bardou-Jacquet1, Jeff Morcet2, Ghislain Manet2, Fabrice Lainé3, Michèle Perrin2, Anne-Marie Jouanolle4, Dominique Guyader5, Romain Moirand5, Jean-François Viel6, Yves Deugnier7. 1. CHU Rennes, Service des maladies du foie, Rennes, France; INSERM, U991, Hôpital Pontchaillou, Rennes, France. Electronic address: edouard.bardou-jacquet@chu-rennes.fr. 2. INSERM, CIC 1414, Hôpital Pontchaillou, Rennes, France. 3. CHU Rennes, Service des maladies du foie, Rennes, France; INSERM, CIC 1414, Hôpital Pontchaillou, Rennes, France. 4. CHU Rennes, Service de génétique moléculaire, Rennes, France. 5. CHU Rennes, Service des maladies du foie, Rennes, France; INSERM, U991, Hôpital Pontchaillou, Rennes, France; University of Rennes 1, UFR médecine, Rennes, France. 6. University of Rennes 1, UFR médecine, Rennes, France; CHU Rennes, Service d'épidémiologie et de santé publique, Hôpital Pontchaillou, Rennes, France. 7. CHU Rennes, Service des maladies du foie, Rennes, France; INSERM, U991, Hôpital Pontchaillou, Rennes, France; INSERM, CIC 1414, Hôpital Pontchaillou, Rennes, France; University of Rennes 1, UFR médecine, Rennes, France.
Abstract
BACKGROUND & AIMS: Mortality studies in patients with hemochromatosis give conflicting results especially with respect to extrahepatic causes of death. Our objective was to assess mortality and causes of death in a cohort of patients homozygous for the C282Y mutation in the HFE gene, diagnosed since the availability of HFE testing. METHODS: We studied 1085 C282Y homozygotes, consecutively diagnosed from 1996 to 2009, and treated according to current recommendations. Mortality and causes of death were obtained from death certificates and compared to those of the general population. Standardized mortality ratios (SMRs) were used to assess specific causes of death and the Cox model was used to identify prognostic factors for death. RESULTS: Patients were followed for 8.3±3.9 years. Overall the SMR was the same as in the general population (0.94 CI: 0.71-1.22). Patients with serum ferritin⩾2000 μg/L had increased liver-related deaths (SMR: 23.9 CI: 13.9-38.2), especially due to hepatic cancer (SMR: 49.1 CI: 24.5-87.9). Patients with serum ferritin between normal and 1000 μg/L had a lower mortality than the general population (SMR: 0.27 CI: 0.1-0.5), due to a decreased mortality, related to reduced cardiovascular events and extrahepatic cancers in the absence of increased liver-related mortality. Age, diabetes, alcohol consumption, and hepatic fibrosis were independent prognostic factors of death. CONCLUSIONS: In treated HFE hemochromatosis, only patients with serum ferritin higher than 2000 μg/L have an increased mortality, mainly related to liver diseases. Those with mild iron burden have a decreased overall mortality in relation to reduced cardiovascular and extrahepatic cancer-related events. These results support a beneficial effect of early and sustained management of patients with iron excess, even when mild.
BACKGROUND & AIMS: Mortality studies in patients with hemochromatosis give conflicting results especially with respect to extrahepatic causes of death. Our objective was to assess mortality and causes of death in a cohort of patients homozygous for the C282Y mutation in the HFE gene, diagnosed since the availability of HFE testing. METHODS: We studied 1085 C282Y homozygotes, consecutively diagnosed from 1996 to 2009, and treated according to current recommendations. Mortality and causes of death were obtained from death certificates and compared to those of the general population. Standardized mortality ratios (SMRs) were used to assess specific causes of death and the Cox model was used to identify prognostic factors for death. RESULTS:Patients were followed for 8.3±3.9 years. Overall the SMR was the same as in the general population (0.94 CI: 0.71-1.22). Patients with serum ferritin⩾2000 μg/L had increased liver-related deaths (SMR: 23.9 CI: 13.9-38.2), especially due to hepatic cancer (SMR: 49.1 CI: 24.5-87.9). Patients with serum ferritin between normal and 1000 μg/L had a lower mortality than the general population (SMR: 0.27 CI: 0.1-0.5), due to a decreased mortality, related to reduced cardiovascular events and extrahepatic cancers in the absence of increased liver-related mortality. Age, diabetes, alcohol consumption, and hepatic fibrosis were independent prognostic factors of death. CONCLUSIONS: In treated HFE hemochromatosis, only patients with serum ferritin higher than 2000 μg/L have an increased mortality, mainly related to liver diseases. Those with mild iron burden have a decreased overall mortality in relation to reduced cardiovascular and extrahepatic cancer-related events. These results support a beneficial effect of early and sustained management of patients with iron excess, even when mild.
Authors: Sim Yee Ong; Lara Dolling; Jeannette L Dixon; Amanda J Nicoll; Lyle C Gurrin; Michelle Wolthuizen; Erica M Wood; Greg J Anderson; Grant A Ramm; Katrina J Allen; John K Olynyk; Darrell Crawford; Jennifer Kava; Louise E Ramm; Paul Gow; Simon Durrant; Lawrie W Powell; Martin B Delatycki Journal: BMJ Open Date: 2015-08-12 Impact factor: 2.692
Authors: Paul Adams; Albert Altes; Pierre Brissot; Barbara Butzeck; Ioav Cabantchik; Rodolfo Cançado; Sonia Distante; Patricia Evans; Robert Evans; Tomas Ganz; Domenico Girelli; Rolf Hultcrantz; Gordon McLaren; Ben Marris; Nils Milman; Elizabeta Nemeth; Peter Nielsen; Brigitte Pineau; Alberto Piperno; Graça Porto; Dianne Prince; John Ryan; Mayka Sanchez; Paulo Santos; Dorine Swinkels; Emerência Teixeira; Ketil Toska; Annick Vanclooster; Desley White Journal: Hepatol Int Date: 2018-03-27 Impact factor: 6.047
Authors: Bhavika Parmanand; Michael Watson; Karen J Boland; Narayan Ramamurthy; Victoria Wharton; Alireza Morovat; Elizabeth K Lund; Jane Collier; Gwenaelle Le Gall; Lee Kellingray; Susan Fairweather-Tait; Jeremy F Cobbold; Arjan Narbad; John D Ryan Journal: JHEP Rep Date: 2020-07-28