title: Hemochromatosis gene mutations in chronic hepatitis C patients with and without liver siderosis.
abstract: Chronic hepatitis C is often associated with liver iron overload, which may affect the long-term prognosis and the response to antiviral treatment. The occurrence of hemochromatosis (HFE) mutations were studied to determine whether may contribute to the liver iron overload of chronic hepatitis C patients. The prevalence of two HFE mutations (C282Y and H63D) in 120 chronic hepatitis C patients was determined and the findings were correlated with clinical, histological and virological features. Hepatic iron was determined semiquantitatively by a histochemical hepatic iron index, defined as the ratio of a histochemical staining score to the patient's age, after correction for heterogeneous lobular iron distribution. Serum hepatitis C virus (HCV) RNA was measured by bDNA assay and typed by restriction fragment length polymorphism. Liver HCV RNA was measured by a semi-quantitative strand-specific reverse transcription-polymerase chain reaction (RT-PCR). Excess liver iron was stained in the liver of 36 patients (30%). Siderotic patients had the same geographic origin, serum and liver HCV RNA levels and H63D and C282Y mutations frequency as non-siderotic patients. However, siderotic patients were older (P = 0.015), more frequently males (P = 0.02), less frequently infected with HCV genotype 3 (P = 0.037) and had a higher liver fibrosis score (P = 0.008). The liver iron content did not correlate with the serum or liver HCV RNA titers. Ten of the 36 patients with liver siderosis had neither a history of excess alcohol intake, multiple transfusions, or HFE mutations. In conclusion, the pathogenesis of the liver iron overload in chronic hepatitis C patients cannot be fully explained by the occurrence of HFE mutations. The exact mechanism of iron accumulation in these patients therefore remains unexplained.
authors.affiliation: Divisions of Gastroenterology and Hepatology, University Hospital, Geneva. Francesco.Negro@dim.hcuge.ch
authors.forename: F
authors.initials: F
authors.lastname: Negro
authors.forename: K
authors.initials: K
authors.lastname: Samii
authors.forename: L
authors.initials: L
authors.lastname: Rubbia-Brandt
authors.forename: R
authors.initials: R
authors.lastname: Quadri
authors.forename: P J
authors.initials: PJ
authors.lastname: Male
authors.forename: J P
authors.initials: JP
authors.lastname: Zarski
authors.forename: M
authors.initials: M
authors.lastname: Baud
authors.forename: E
authors.initials: E
authors.lastname: Giostra
authors.forename: P
authors.initials: P
authors.lastname: Beris
authors.forename: A
authors.initials: A
authors.lastname: Hadengue
mesh_terms: D000328:Adult; D000368:Aged; D005260:Female; D006432:Hemochromatosis / Q000235:genetics*; D016174:Hepacivirus / Q000235:genetics / Q000302:isolation & purification; D019698:Hepatitis C, Chronic / Q000150:complications* / Q000235:genetics* / Q000821:virology; D006801:Humans; D007371:Interferon-gamma / Q000627:therapeutic use; D007501:Iron / Q000032:analysis; D019190:Iron Overload / Q000188:drug therapy / Q000209:etiology* / Q000473:pathology; D008099:Liver / Q000737:chemistry / Q000473:pathology / Q000821:virology; D008107:Liver Diseases / Q000188:drug therapy / Q000209:etiology / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D012367:RNA, Viral / Q000097:blood; D012806:Siderosis / Q000188:drug therapy / Q000209:etiology* / Q000473:pathology
chemical_list: D012367:RNA, Viral; D007371:Interferon-gamma; D007501:Iron