Hemochromatosis gene mutations in chronic hepatitis C patients with and without liver siderosis

J Med Virol. 2000 Jan;60(1):21-7.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Female
  • Hemochromatosis / genetics*
  • Hepacivirus / genetics
  • Hepacivirus / isolation & purification
  • Hepatitis C, Chronic / complications*
  • Hepatitis C, Chronic / genetics*
  • Hepatitis C, Chronic / virology
  • Humans
  • Interferon-gamma / therapeutic use
  • Iron / analysis
  • Iron Overload / drug therapy
  • Iron Overload / etiology*
  • Iron Overload / pathology
  • Liver / chemistry
  • Liver / pathology
  • Liver / virology
  • Liver Diseases / drug therapy
  • Liver Diseases / etiology
  • Liver Diseases / pathology
  • Male
  • Middle Aged
  • Mutation*
  • RNA, Viral / blood
  • Siderosis / drug therapy
  • Siderosis / etiology*
  • Siderosis / pathology

Substances

  • RNA, Viral
  • Interferon-gamma
  • Iron