Clinical impact of HFE mutations in Japanese patients with chronic hepatitis C

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Abstract

BACKGROUND AND AIM: HFE mutations, a common cause of hereditary hemochromatosis (HH), are reportedly associated with hepatic iron overload, severe liver fibrosis, and good response to interferon treatment in European patients with chronic hepatitis C (CHC). HH shows ethnicity-based differences and little is known about the effects of HH mutations on CHC in the Japanese. Thus, the aim of this study was to clarify the clinical influence of HFE mutations in Japanese CHC patients.<br /><br />METHODS: In a total of 251 patients with CHC, we analyzed the frequencies of H63D and S65C mutations in the HFE gene, and the influence of these mutations on clinical parameters and response to pegylated-interferon-alpha 2b (PEG-IFN) plus ribavirin therapy.<br /><br />RESULTS: Fourteen patients (5.6%) carried the H63D mutation; all were heterozygotes. No S65C mutations were found. Only hemoglobin levels in the H63D heterozygotes were higher than in wild-type patients. Eleven of 14 H63D heterozygotes achieved sustained virological response (SVR). On univariate analysis, factors associated with SVR were interleukin 28B (IL28B) polymorphism, age, hepatitis C virus (HCV) genotype, HCV viral load, white blood cell count, stage of fibrosis and H63D mutation. All patients with both TT genotype in IL28B (rs8099917) and H63D mutation in HFE (n = 10) achieved SVR.<br /><br />CONCLUSIONS: The H63D mutation has little impact on the clinical characteristics of CHC, but is related to favorable response to PEG-IFN plus ribavirin therapy, particularly in patients with the TT allele in IL28B.

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Ishizu, Y., Katano, Y., Honda, T., Hayashi, K., Ishigami, M., Itoh, A., … Goto, H. (2012). Clinical impact of HFE mutations in Japanese patients with chronic hepatitis C. Journal of Gastroenterology and Hepatology (Australia), 27(6), 1112–1116. https://doi.org/10.1111/j.1440-1746.2011.06976.x

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