Clinical impact of HFE mutations in Japanese patients with chronic hepatitis C.
Clinical impact of HFE mutations in Japanese patients with chronic hepatitis C.
复制标题
HFE 突变对日本慢性丙型肝炎患者的临床影响。
DOI：
10.1111/j.1440-1746.2011.06976.x
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发表时间：
2012
期刊：
影响因子：
--
通讯作者：
Goto H.
中科院分区：
文献类型：
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作者：
Ishizu Y;Katano Y;Honda T;Hayashi K;Ishigami M;Itoh A;Hirooka Y;Nakano I;Goto H.
背景和目的：HFE突变是遗传性血色沉着症(HH)的常见原因，据报道，在欧洲慢性丙型肝炎(CHC)患者中，HFE突变与肝脏铁超载、严重的肝纤维化和对干扰素治疗的良好反应有关。HH表现出基于种族的差异，对于HH突变对日本人CHC的影响知之甚少。方法：在251例CHC患者中，我们分析了HFE基因H63D和S65C突变的频率，以及这些突变对临床参数和对聚乙二醇化干扰素-α2b(PEG化干扰素-α2b)联合利巴韦林治疗的影响。结果：14例患者(5.6%)携带H63D突变，均为杂合子。未发现S65C突变。只有H63D杂合子患者的血红蛋白水平高于野生型患者。14个H63D杂合子中有11个获得持续病毒学应答(SVR)。单因素分析显示，白细胞介素28B(IL28B)基因多态性、年龄、丙型肝炎病毒(HCV)基因分型、病毒载量、白细胞计数、肝纤维化分期、H63D变异与SVR相关。所有同时携带IL28B基因TT型(Rs8099917)和HFE基因H63D突变的患者(n= 10)均获得SVR。结论：H63D突变对慢性丙型肝炎的临床特征影响不大，但与干扰素联合利巴韦林治疗效果良好有关，尤其是携带IL28B基因TT等位基因的患者。
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.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.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.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.