The role of iron and haemochromatosis gene mutations in the progression of liver disease in chronic hepatitis C

Area of Science:

• Hepatology and Gastroenterology
• Genetics and Genomics
• Infectious Diseases

Background:

• Chronic hepatitis C virus (HCV) infection often presents with elevated iron stores.
• HFE gene mutations, causative in hereditary hemochromatosis, are investigated for their potential role in HCV.
• The association between HFE mutations and liver fibrosis in HCV is debated.

Purpose of the Study:

• To determine the prevalence of HFE mutations in Scottish patients with HCV.
• To examine the influence of HFE mutation carrier status on iron stores and liver disease severity in HCV patients.

Main Methods:

• Prospective assessment of 164 HCV antibody-positive patients undergoing liver biopsy.
• Screening for HFE mutations (Cys282Tyr, His63Asp) and assessment of serum iron markers (ferritin, transferrin saturation).
• Evaluation of liver iron markers including stainable iron, liver iron concentration (LIC), and hepatic iron index.

Main Results:

• HFE mutations were found in 41% of patients (heterozygotes).
• Elevated serum iron markers were observed in 28%, with 15% showing stainable liver iron and 3% elevated LICs.
• HFE mutation carriage did not correlate with iron accumulation or liver disease severity; elevated iron markers and LICs were associated with more severe liver disease, male sex, alcohol consumption, and inflammation.

Conclusions:

• Elevated serum iron markers are common in chronic HCV, but elevated liver iron concentration (LIC) is infrequent.
• More severe liver disease in HCV patients is linked to elevated iron studies and LICs.
• HFE gene mutations are prevalent but do not contribute to iron accumulation or disease progression in HCV infection.