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The term hemochromatosis (HC) corresponds to several diseases characterized by systemic iron overload of genetic origin and affecting both the quality of life and life expectancy. Major improvement in the knowledge of iron metabolism permits to divide these diseases into two main pathophysiological categories. For most HC forms (types 1, 2, 3 and 4B HC) iron overload is related to cellular hepcidin deprivation which causes an increase of plasma iron concentration and the appearance of plasma non-transferrin bound iron. In contrast, iron excess in type 4A ferroportin disease is related to decreased cellular iron export. Whatever the HC type, the diagnosis rests on a non-invasive strategy, combining clinical, biological and imaging data. The mainstay of the treatment remains venesection therapy with the perspective of hepcidin supplementation for hepcidin deprivation-related HC. Prevention of HC is critical at the family level and, for type 1 HC, remains a major goal, although still debated, at the population level., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)

Background: The treatment of HFE-related hemochromatosis, one of the most common genetic diseases, is based on phlebotomies whose tolerance is evaluated by regular monitoring of hemoglobin. Using a portable hemoglobinometer (PH) could provide an easy and fast determination of hemoglobin. Therefore, the aim of the present study was to compare, in hemochromatosis patients treated by bloodletting, the hemoglobin concentrations as assayed, on capillary blood, by a PH device and, on venous blood, by a cell counter (CC) device., Methods: For a total period of 12 weeks duration, all patients undergoing phlebotomies in the same hospital outpatient unit had hemoglobin determinations both by the HemoCue and by the laboratory's DxH 800 Coulter. To evaluate the sensitivity and specificity of the HemoCue, patients were classified as presenting or not anemia as defined by hemoglobin level below 11 g/dl., Results: Measurements of hemoglobin were performed in 122 patients. The sensitivity and specificity of PH compared to CC were 100 and 98.1%, respectively. Capillary hemoglobin by PH slightly underestimated venous hemoglobin by CC. The Pearson's correlation coefficient between PH and CC was 0.80 (P<0.0001)., Conclusion: PH is a reliable, quick and easy technology, which can be proposed to follow-up the tolerance of venesections in hemochromatosis patients., (Copyright © 2015 Elsevier Masson SAS. All rights reserved.)

Rare genetic iron overload diseases are an evolving field due to major advances in genetics and molecular biology. Genetic iron overload has long been confined to the classical type 1 hemochromatosis related to the HFE C282Y mutation. Breakthroughs in the understanding of iron metabolism biology and molecular mechanisms led to the discovery of new genes and subsequently, new types of hemochromatosis. To date, four types of hemochromatosis have been identified: HFE-related or type1 hemochromatosis, the most frequent form in Caucasians, and four rare types, named type 2 (A and B) hemochromatosis (juvenile hemochromatosis due to hemojuvelin and hepcidin mutation), type 3 hemochromatosis (related to transferrin receptor 2 mutation), and type 4 (A and B) hemochromatosis (ferroportin disease). The diagnosis relies on the comprehension of the involved physiological defect that can now be explored by biological and imaging tools, which allow non-invasive assessment of iron metabolism. A multidisciplinary approach is essential to support the physicians in the diagnosis and management of those rare diseases., (Copyright © 2013 Elsevier Masson SAS. All rights reserved.)

We report here the first case of chronic cytolysis that led to the diagnosis of pheochromocytoma, in a 48-year-old woman with a recent onset of hypertension. The etiological research ruled out the common causes of raised transaminase levels, and led to the discovery of a left adrenal pheochromocytoma. The sustained normalization of liver function tests after the removal of the tumour strongly suggests that hepatocyte injury was due to catecholamine hyperproduction. The present original clinical case, linking pheochromocytoma and liver dysfunction, raises important mechanistic questions concerning the relationship between catecholamines and liver function. It may also have clinical implications. Indeed, pheochromocytoma should be considered as a possible cause in case of unexplained transaminase increase associated with the recent onset of hypertension., (Copyright © 2012 Elsevier Masson SAS. All rights reserved.)

Haemochromatoses encompass a variety of genetic iron overload diseases. The most frequent entity remains HFE-related haemochromatosis. The other syndromes include diseases related to mutations of the hemojuvelin, hepcidin, transferrin receptor 2 and ferroportin genes. Iron excess is due to deficiencies in either hepcidin or ferroportin, the two key regulatory proteins of iron metabolism. Diagnosis rests essentially upon non invasive clinical, biological and imaging criteria. The mainstay of iron overload treatment is venesection therapy in case of hepcidin deficiency, the therapeutic approach for the future being hepcidin supplementation. In ferroportin deficiency, oral chelation is an interesting orientation. The recent creation in France of a reference center and of several competence centers for rare genetic iron overload diseases represents a valuable organization for improving both the understanding of the diseases and the management of the patients.

Phenotypic expression of the homozygous C282Y/C282Y mutation of the HFE gene has been classified in five stages, and appropriate management recommended for each stage. Phlebotomy is indicated for stages>or=2, that is, with elevated transferrin saturation and serum ferritin levels >300 microg/L in men and >200 microg/L in women. Maximal volume per phlebotomy is 7 mL/kg and should not exceed 550 mL. The main goal of this iron-depletion therapy is to reach and maintain serum ferritin levels

Hereditary type 1 HFE hemochromatosis is associated with homozygosity for the p.Cys282Tyr mutation of the HFE gene (C282Y mutation). The p.Cys282Tyr mutation of the HFE gene leads to an abnormal reduction in hepatic expression of hepcidin, a protein that appears to control the release of iron from enterocytes and macrophages towards plasma. Abnormally low hepcidin levels promote an increase in the bioavailability of plasma iron, characterized by elevated transferrin saturation and the appearance of non transferrin bound iron. This nontransferrin-bound iron is avidly taken up by the liver, heart, and pancreas, the principal target organs for systemic iron overload. The variable penetrance of this disease is related to environmental and genetic factors. Among the genetic factors, mutations of some newly identified genes may aggravate the phenotype of iron overload associated with homozygosity for the p.Cys282Tyr mutation of the HFE gene; these new genes include those of hemojuvelin (HJV), transferrin receptor 2 (TfR2), and hepcidin (HAMP).

Aim: To determine the diagnostic value of systematic liver needle biopsy and endoscopic retrograde cholangiography in patients with unexplained chronic anicteric cholestasis., Methods: Seventy nine patients presented with anicteric cholestasis for over 6 months as defined by: a concomitant increase in at least 2 of 3 cholestatic enzymes (GGT, alkaline phosphatase, 5'nucleotidase); a low cytolytic ratio (ALT/AP (xN/xN) < or = 5); and negative test results (normal ultrasound scan; no antimitochondrial antibodies, viral, drug-induced, or toxic hepatitis, or known ulcerative cholitis). Based on liver biopsy and endoscopic retrograde cholangiography, 5 groups were determined; group A: normal liver biopsy and endoscopic retrograde cholangiography; group B: primary sclerosing cholangitis with histological biliary lesions; group C: primary sclerosing cholangitis with normal histology; group D: histologic biliary lesions alone; group E: other (aspecific histologic lesions, isolated anomalies of intrahepatic bile ducts on endoscopic retrograde cholangiography)., Results: Diagnosis of cholestasis was fortuitous in 43% of cases. Group A: 5 patients had normal liver biopsy and endoscopic retrograde cholangiography; group B (10 patients): 5 with destructive cholangitis, 5 with degenerative cholangitis, associated with portal fibrosis in 90%; group C: none of the patients had primary sclerosing cholangitis with normal histology; group D: 39 patients {idiopathic ductopenia (1), Caroli's disease (1), benign recurrent cholestasis (1), regenerative nodular hyperplasia (4), destructive cholangitis without ductopenia (7), degenerative cholangitis (15), ductular proliferation (10)}; group E: 24 patients with aspecific histologic lesions, and one patient with isolated anomalies of the intrahepatic bile ducts on endoscopic retrograde cholangiography., Conclusions: In the present population: a) 13% presented with intense cholangitis and primary sclerosing cholangitis on endoscopic retrograde cholangiography; b) 49% presented with various histologic biliary lesions without primary sclerosing cholangitis. We conclude that in chronic anicteric cholestasis of unexplained origin, first choice work-up should include liver biopsy, and endoscopic retrograde cholangiography should only be performed when intense histologic cholangitis is observed.

Unlabelled: The evolution of epidemiological data on hepatitis C virus infection is poorly documented and thus the impact of screening is difficult to evaluate., Aim: To study epidemiological variations based on the origin of transmission and the year of diagnosis of hepatitis C virus infection., Methods: The files of all 1304 patients seen in the hepatology unit of the Rennes University Hospital were analyzed (retrospectively before and prospectively after October 1995) in relation to epidemiological features., Results: Despite widespread screening which is the source of 60% of the diagnoses, the total number of new cases of hepatitis C infection per year has not increased. Compared to patients diagnosed in the first years following the discovery of the virus, patients recently identified were younger (42 +/- 14 years) and frequently drug addicts (40%). Aminotransaminases were normal in 20% of cases. The frequency of cirrhosis has declined (17%). There has been a decrease in the proportion of patients who undergo liver biopsy (50%) and treatment with interferon (one third of patients)., Conclusions: The impact of screening on the number of newly treated patients seems to be lower than previously predicted.

Ultrasonically guided fine needle aspiration biopsy is known to be of great value in the diagnosis of malignant liver disease, with an overall accuracy rate of 73-94 p. 100. However, investigators have essentially reported cases of liver metastases. In this report, we examined the diagnostic value of this method in the specific case of tumors associated with cirrhosis. Twenty-seven patients with cirrhosis (20 alcoholic, 4 post-hepatitis, 3 hemochromatosis) with ultrasonically suspected hepatic malignancy were studied. They all presented severe blood clotting disturbances and/or ascites. At the end of the study, all patients had proven malignancy (by post mortem biopsy in 14 cases and/or serum AFP greater than 500 microgram/l in 17 cases). There were 25 primary and 2 metastatic tumors. Twenty-nine fine needle aspiration biopsies were performed under ultrasonic guidance. material suitable for cytologic evaluation was obtained in 25 patients. In 14 cases, a diagnosis of malignant involvement of the liver was firmly established by cytological examination; it was suggested in 4 other cases. Tumor typing was possible in 12 primary and 2 metastatic tumors, in agreement with the proven diagnosis. The present study shows that fine needle aspiration biopsy under ultrasound guidance is a safe and accurate diagnostic procedure in malignant liver disease associated with cirrhosis.