Iron levels in hepatocytes and portal tract cells predict progression and outcomes of patients with advanced chronic hepatitis C.
Iron levels in hepatocytes and portal tract cells predict progression and outcomes of patients with advanced chronic hepatitis C.
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DOI：
10.1053/j.gastro.2011.01.053
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发表时间：
2011-05
期刊：
影响因子：
29.4
通讯作者：
HALT-C Trial Group
中科院分区：
文献类型：
--
作者：
Lambrecht RW;Sterling RK;Naishadham D;Stoddard AM;Rogers T;Morishima C;Morgan TR;Bonkovsky HL;HALT-C Trial Group
铁可能影响非血色肝病的严重程度和进展。我们使用HALT-C试验的数据评估了铁、HFE变体与进展和结局之间的关系。我们确定了聚乙二醇干扰素（PegIFN）治疗是否影响铁变量。参与者被随机分配到接受PegIFN长期治疗（n=400）或未接受治疗（n=413）的组，持续3.5年，随访时间长达8.7年（中位数6.0年）。采用Kaplan-Meier分析、考克斯回归模型和重复测量协方差分析，研究患者特征与铁变量之间的关系，包括基线和随时间的变化。普鲁士蓝染色检测铁。结果较差的患者（Child-Turcotte-Pugh评分增加至≥ 7，发生腹水、脑病、静脉曲张出血、自发性细菌性腹膜炎、肝细胞癌、死亡）的肝细胞和汇管区细胞中铁蛋白的基线评分显著高于无结果的患者。门脉三联中的铁染色与小叶和总Ishak炎症和纤维化评分相关（P<0.0001）。三联征患者基线水平高的铁水平增加了不良结局的风险（风险比=1.35，P=0.02）。铁染色在肝细胞中随时间减少，但在门静脉基质细胞中随时间增加（P<0.0001）。血清铁和总铁结合力随时间显著降低（P <0.0001），血清铁蛋白也是如此（P=0.0003）。用聚乙二醇干扰素长期治疗不影响铁染色水平。HFE的常见变异与结局（包括肝细胞癌的发生）无关。肝细胞和门脉束细胞中的铁蛋白水平可预测晚期慢性丙型肝炎患者的进展及临床和组织学结局。低剂量聚乙二醇干扰素长期治疗并不能改善结果或铁变量。
Iron might influence severity and progression of non-hemochromatotic liver diseases. We assessed the relationships between iron, variants in HFE, and progression and outcomes using data from the HALT-C Trial. We determined whether therapy with pegylated interferon (PegIFN) affects iron variables. Participants were randomly assigned to groups given long-term therapy with PegIFN (n=400) or no therapy (n=413) for 3.5 y and followed for up to 8.7 y (median 6.0 y). Associations between patient characteristics and iron variables, at baseline and over time, were made using Kaplan-Meier analyses, Cox regression models, and repeated measures analysis of covariance. Iron was detected by Prussian blue staining. Patients with poor outcomes (increase in Child-Turcotte-Pugh score to ≥ 7, development of ascites, encephalopathy, variceal bleeding, spontaneous bacterial peritonitis, hepatocellular carcinoma, death) had significantly higher baseline scores for stainable iron in hepatocytes and cells in portal tracts than those without outcomes. Staining for iron in portal triads correlated with lobular and total Ishak inflammatory and fibrosis scores (P<0.0001). High baseline levels of iron in triads increased the risk for poor outcome (hazard ratio=1.35, P=0.02). Iron staining decreased in hepatocytes but increased in portal stromal cells over time (P<0.0001). Serum levels of iron and total iron binding capacity decreased significantly over time (P <0.0001), as did serum ferritin (P=0.0003). Long-term therapy with PegIFN did not affect levels of iron staining. Common variants in HFE did not correlate with outcomes, including development of hepatocellular carcinoma. Degree of stainable iron in hepatocytes and portal tract cells predicts progression and clinical and histological outcomes of patients with advanced chronic hepatitis C. Long-term therapy with low-dose PegIFN did not improve outcomes or iron variables.
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影响因子：
3.1
作者：
Desai, Tusar K.;Jamil, Laith H.;Bonkovsky, Herbert L.
通讯作者：
Bonkovsky, Herbert L.
影响因子：
158.5
作者：
Adams, PC;Reboussin, DM;Thomson, E
通讯作者：
Thomson, E
影响因子：
13.5
作者：
FARGION, S;MANDELLI, C;CONTE, D
通讯作者：
CONTE, D
DOI：
10.1016/j.cct.2004.08.003
发表时间：
2004-10-01
期刊：
CONTROLLED CLINICAL TRIALS
影响因子：
--
作者：
Lee, WM;Dienstag, JL;Everhart, JE
通讯作者：
Everhart, JE
影响因子：
29.4
作者：
Kowdley, KV;Brandhagen, DJ;Polissar, N
通讯作者：
Polissar, N