Smith B C, Gorve J, Guzail M A, Day C P, Daly A K, Burt A D, Bassendine M F
Centre for Liver Research, University of Newcastle upon Tyne, England, UK.
Hepatology. 1998 Jun;27(6):1695-9. doi: 10.1002/hep.510270631.
Hepatic iron has been associated with more aggressive liver disease in chronic viral hepatitis. We evaluated whether the recently described C282Y mutation of the hemochromatosis gene, designated HFE (responsible for at least 83% of hereditary hemochromatosis), was associated with more advanced liver disease in chronic hepatitis C. One hundred thirty-seven patients with biopsy-proven chronic hepatitis C were studied and liver biopsies scored for necroinflammation (grade 0-18) and fibrosis (stage 0-6). Genomic DNA was amplified by polymerase chain reaction and the C282Y mutation identified by restriction with RsaI and electrophoretic separation of restriction fragments. Ten (7.3%) patients had the C282Y mutation. No C282Y homozygous patients were identified. Age, sex distribution, and estimated weekly alcohol consumption were not significantly different between those with and without the mutation. Serum ferritin was higher in the heterozygotes (mean, 339 microg/L) compared with homozygous wild types (153 microg/L; P = .0005). In the majority of patients, liver iron was graded 0 out of 4, but hepatocyte iron staining was more commonly present in heterozygotes compared with homozygous normals (30% compared with 4% [P = .02]). Liver disease was more advanced in those with the mutant allele (mean fibrosis stage: 3.6, compared with wild type: 1.5 [P = .01]). Cirrhosis was found more often in those with the mutation (40%) compared with those without (8.7%) (P = .01; odds ratio: 7.6 [1.9-31.2]). There was no significant difference in inflammation scores between heterozygotes and wild type (mean, 5.4 compared with 4.1). Hepatitis C virus (HCV)-RNA titers were measured by branched DNA assay (HCV RNA 2.0-Chiron), and there was no difference between heterozygous and homozygous normal patients. Thus, despite relatively minor increases in iron stores, individuals who are heterozygous for hemochromatosis appear to develop more fibrosis in chronic hepatitis C. Venesection may be useful therapy in this subgroup.
肝铁与慢性病毒性肝炎中更具侵袭性的肝脏疾病相关。我们评估了最近描述的血色素沉着症基因C282Y突变（该基因命名为HFE，至少83%的遗传性血色素沉着症与之相关）是否与丙型肝炎中更严重的肝脏疾病有关。对137例经活检证实为慢性丙型肝炎的患者进行了研究，并对肝活检标本进行坏死性炎症（0 - 18级）和纤维化（0 - 6期）评分。通过聚合酶链反应扩增基因组DNA，并用RsaI酶切和限制性片段的电泳分离来鉴定C282Y突变。10例（7.3%）患者存在C282Y突变。未发现C282Y纯合子患者。有突变和无突变患者在年龄、性别分布及估计每周酒精摄入量方面无显著差异。杂合子的血清铁蛋白水平（平均339μg/L）高于纯合野生型（153μg/L；P = 0.0005）。在大多数患者中，肝铁评分为4分制中的0分，但与纯合正常者相比，杂合子中肝细胞铁染色更常见（分别为30%和4% [P = 0.02]）。携带突变等位基因者的肝脏疾病更严重（平均纤维化分期：3.6，野生型为1.5 [P = 0.01]）。与无突变者（8.7%）相比，有突变者中肝硬化更常见（40%）（P = 0.01；比值比：7.6 [1.9 - 31.2]）。杂合子与野生型在炎症评分上无显著差异（平均分别为5.4和4.1）。通过分支DNA分析法（HCV RNA 2.0 - Chiron）检测丙型肝炎病毒（HCV）-RNA滴度，杂合子与纯合正常患者之间无差异。因此，尽管铁储存量仅有相对较小的增加，但血色素沉着症杂合子个体在慢性丙型肝炎中似乎会出现更多纤维化。静脉放血疗法可能对该亚组患者有用。
