Heterozygosity for hereditary hemochromatosis is associated with more fibrosis in chronic hepatitis C

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Mouse Model of Metabolic Dysfunction-Associated Steatotic Liver Disease with Fibrosis

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B C Smith1, J Gorve, M A Guzail

  • 1Centre for Liver Research, University of Newcastle upon Tyne, England, UK.

Hepatology (Baltimore, Md.)
|June 10, 1998
PubMed

Insights

Hereditary hemochromatosis C282Y mutation carriers with chronic hepatitis C showed increased liver fibrosis and cirrhosis. Even minor iron increases in heterozygotes for hemochromatosis gene HFE may worsen liver disease.

Area of Science:

  • Hepatology
  • Genetics
  • Internal Medicine

Background:

  • Hepatic iron overload is linked to severe liver disease in chronic viral hepatitis.
  • The C282Y mutation in the hemochromatosis gene (HFE) is a common cause of hereditary hemochromatosis.

Purpose of the Study:

  • To investigate the association between the HFE C282Y mutation and advanced liver disease in patients with chronic hepatitis C.
  • To determine if carrying the C282Y mutation influences fibrosis or necroinflammation severity in chronic hepatitis C.

Main Methods:

  • Studied 137 patients with biopsy-proven chronic hepatitis C.
  • Assessed liver biopsies for necroinflammation and fibrosis.
  • Genotyped patients for the HFE C282Y mutation using PCR and restriction fragment analysis.
  • Measured serum ferritin and liver iron staining.

Main Results:

  • Ten patients (7.3%) carried the C282Y mutation; none were homozygous.
  • Heterozygotes had higher serum ferritin and more frequent hepatocyte iron staining.
  • Patients with the mutant allele showed significantly more advanced fibrosis (mean stage 3.6 vs. 1.5) and higher rates of cirrhosis (40% vs. 8.7%).
  • No significant differences were observed in inflammation scores or HCV-RNA titers.

Conclusions:

  • Individuals heterozygous for the HFE C282Y mutation experience more advanced liver fibrosis and cirrhosis in chronic hepatitis C.
  • Minor increases in iron stores associated with hemochromatosis heterozygosity may contribute to more severe liver disease.
  • Venesection (bloodletting) could be a beneficial therapeutic option for this patient subgroup.

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