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Hepatitis C, iron status, and disease severity: Relationship with HFE mutations
Abstract
Background & aims Mild to moderate hepatic iron loading is common in patients with chronic hepatitis C. We sought to determine whether mutations in the hemochromatosis gene, HFE, are associated with iron overload and acceleration of disease progression in hepatitis C patients.Methods A total of 316 patients with chronic hepatitis C were studied: 198 consecutive patients undergoing liver biopsy for compensated liver disease and 118 who underwent liver transplantation for end-stage liver disease. Serum iron studies, quantitative hepatic iron concentration, histologic activity index, and HFE genotype were determined.Results Among patients with compensated liver disease, the presence of HFE mutations was independently associated with elevations in serum iron level, serum transferrin-iron saturation, serum ferritin level, and hepatic iron index (P < 0.05). After adjustment for duration of infection with hepatitis C virus, HFE mutations were also independently associated with the presence of bridging fibrosis or cirrhosis (odds ratio, 18; 95% confidence interval, 1.7-193). HFE mutations were not independently associated with iron loading in patients with end-stage liver disease. There was no significant difference in the prevalence of HFE mutations between patients with compensated and end-stage liver disease (42% vs. 33%, respectively; P = 0.67).Conclusions The presence of HFE mutations is independently associated with iron loading and advanced fibrosis in patients with compensated liver disease from chronic hepatitis C, especially after controlling for duration of disease. These results suggest that HFE mutations accelerate hepatic fibrosis in hepatitis C but may not be responsible for progression to end-stage liver disease.
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In alcoholic liver disease, both iron and alcohol contribute to the production of hepatic fibrosis.
“Specifically, in alcoholic liver disease, both iron and alcohol contribute to the production of hepatic fibrosis [1352-1358].”
From Iron behaving badly: inappropriate iron chelation as a major contributor to the aetiology of vascular and other progressive inflammatory and degenerative diseases (2009) · cites this paper as [1354]
HCV infection suppresses hepcidin expression, contributing to iron overload.
“HCV infection suppresses hepcidin expression, contributing to iron overload”
From Hepcidin and Host Defense against Infectious Diseases (2015) · cites this paper as [85]
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Metadata
- Authors
- Tung, B. Y., Emond, M. J., Bronner, M. P., Raaka, S. D., Cotler, S. J., & Kowdley, K. V.
- Affiliations
- University of Washington (US)
- Corresponding author
- Kowdley, Kris V.
- Venue
- Gastroenterology
- Publisher
- Elsevier BV
- Published
- 2003-02
- Volume
- 124
- Issue
- 2
- Pages
- 318-326
- ISSN
- 0016-5085 (ISSN-L)
- OpenAlex
- W2078515174
- Cited by
- 154
- References
- 0
- Citations by year
- 2023: 2 · 2022: 1 · 2021: 4 · 2020: 1 · 2019: 4 · 2018: 2 · 2017: 5 · 2016: 6 · 2015: 4 · 2014: 7 · 2013: 9 · 2012: 8
- FWCI
- 10.43
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Gastroenterology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Diabetes and Digestive and Kidney Diseases (K24 DK-02957, K24DK002957)
- Topics
- Health Sciences › Medicine › Hepatology › Hepatitis C virus research
- Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Keywords
- chronic hepatitis C, HFE gene mutations, hemochromatosis, hepatic iron overload, iron status, disease progression, liver fibrosis, liver cirrhosis, end-stage liver disease, liver transplantation, serum iron, ferritin, histologic activity index
- MeSH terms
- Hemochromatosis Protein, Female, Gene Frequency, Genotype, Humans, Iron, Liver, Liver Cirrhosis, Male, Membrane Proteins, Middle Aged, Mutation, Severity of Illness Index, Time Factors, Transferrin, Histocompatibility Antigens Class I, Liver Failure, Disease Progression, Hepatitis C, Chronic
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