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首页> 外文期刊>Hepatology: Official Journal of the American Association for the Study of Liver Diseases >Ductular reaction in hereditary hemochromatosis: The link between hepatocyte senescence and fibrosis progression
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Ductular reaction in hereditary hemochromatosis: The link between hepatocyte senescence and fibrosis progression

机译：遗传性血色素沉着症的导管反应：肝细胞衰老与纤维化进程之间的联系

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摘要

The development of portal fibrosis following the iron loading of hepatocytes is the first stage of fibrogenesis in hereditary hemochromatosis. In other chronic liver diseases it has been shown that a ductular reaction (DR) appears early, correlates with fibrosis progression, and is a consequence of activation of an alternative pathway of hepatocyte replication. This study was designed to investigate the presence of the DR in hemochromatosis and describe its associations. Liver biopsies from 63 C282Y homozygous patients were assessed for hepatic iron concentration (HIC) and graded for iron loading, fibrosis stage, steatosis, and inflammation. Immunostaining allowed quantification of the DR, hepatocyte senescence and proliferation, and analysis incorporated clinical data. Hepatocyte senescence was positively correlated with HIC, serum ferritin, and oxidative stress. A DR was demonstrated and occurred prior to histological fibrosis. HIC, age, hepatocyte senescence and proliferation, portal inflammation, and excessive alcohol consumption all had significant associations with the extent of the DR. In multivariate analysis, iron loading, hepatocyte replicative arrest, and portal inflammation remained independently and significantly associated with the DR. Of factors associated with fibrosis progression, the DR (odds ratio [OR] 10.86 P<0.0001) and the presence of portal inflammation (OR 4.31, P=0.028) remained significant after adjustment for cofactors. The extent of the DR regressed following therapeutic venesection. Conclusion: Iron loading of hepatocytes leads to impaired replication, stimulating the development of the DR in hemochromatosis and this correlates strongly with hepatic fibrosis. Portal inflammation occurs in hemochromatosis and is independently associated with the DR and fibrosis, and thus its role in this disease should be evaluated further. (Hepatology 2014;59:848-857).
机译：肝细胞铁负荷后门脉纤维化的发展是遗传性血色素沉着症中纤维化的第一步。在其他慢性肝病中，已显示出导管反应（DR）较早出现，与纤维化进程相关，并且是激活肝细胞复制的另一种途径的结果。本研究旨在调查血色素沉着病中DR的存在并描述其关联。对来自63名C282Y纯合患者的肝活检进行了肝铁浓度（HIC）评估，并对铁负荷，纤维化分期，脂肪变性和炎症进行了分级。免疫染色可以定量DR，肝细胞衰老和增殖，并结合临床数据进行分析。肝细胞衰老与HIC，血清铁蛋白和氧化应激呈正相关。在组织学纤维化之前，DR被证实并发生。 HIC，年龄，肝细胞衰老和增生，门静脉炎症以及过量饮酒均与DR的程度密切相关。在多变量分析中，铁负荷，肝细胞复制停滞和门静脉炎症仍然独立且与DR显着相关。在与纤维化进展相关的因素中，调整辅助因子后，DR（比值比[OR] 10.86 P <0.0001）和门静脉炎症的存在（OR 4.31，P = 0.028）仍然很显着。 DR的程度在治疗性穿刺后下降。结论：肝细胞铁负荷导致复制受损，并刺激血色素沉着病中DR的发展，这与肝纤维化密切相关。门静脉炎症发生在血色素沉着症中，并且与DR和纤维化独立相关，因此应进一步评估其在该疾病中的作用。 （Hepatology 2014; 59：848-857）。

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