Cytokeratin-18 fragment levels as noninvasive biomarkers for nonalcoholic steatohepatitis: a multicenter validation study.
Cytokeratin-18 fragment levels as noninvasive biomarkers for nonalcoholic steatohepatitis: a multicenter validation study.
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细胞角蛋白-18片段水平为非酒精性脂肪性肝炎的无创生物标志物：一项多中心验证研究。
DOI：
10.1002/hep.23050
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发表时间：
2009-10
期刊：
影响因子：
13.5
通讯作者：
McCullough, Arthur J.
中科院分区：
文献类型：
--
作者：
Feldstein, Ariel E.;Wieckowska, Anna;Lopez, A. Rocio;Liu, Yao-Chang;Zein, Nizar N.;McCullough, Arthur J.
肝活检仍然是诊断非酒精性脂肪性肝炎（NASH）的金标准。我们最近证实，血浆细胞角蛋白18（CK - 18）片段水平与肝细胞凋亡程度相关，并能独立预测NASH的存在。我们的目的是验证这种新型生物标志物在NASH诊断中的效用。本研究是NASH临床研究网络（NASH CRN）的一项辅助研究。我们的队列包括来自美国8个中心的139例经活检证实患有非酒精性脂肪性肝病（NAFLD）的患者（他们是CRN的参与者）以及150例年龄匹配的健康对照。使用特异性免疫酶联吸附测定法测量CK - 18片段。由研究病理学家集中评估组织学。与非NASH和临界诊断相比，NASH患者的CK - 18片段显著增加（中位数（第25百分位数，第75百分位数）：分别为335（196，511）、194（151，270）、200（148，284）；P < 0.001）。此外，肝活检出现纤维化的几率随着血浆CK - 18片段水平的升高而增加（P < 0.001）。在多变量回归分析中，在对单变量分析中与CK - 18片段或NASH相关的变量（纤维化、谷丙转氨酶、谷草转氨酶、年龄、活检长度）进行调整后，CK - 18片段仍然是NASH的独立预测因子。NASH诊断的受试者工作特征曲线下面积估计为0.83（0.75，0.91）。
在一大群经活检证实患有NAFLD的不同患者中，血液中CK - 18片段的测定可预测组织学上的NASH以及疾病的严重程度，这支持了该检测在临床实践中的潜在用途。
A liver biopsy remains the gold standard to diagnose nonalcoholic steatohepatitis (NASH). We have recently demonstrated that plasma cytokeratin 18 (CK-18) fragment levels correlate with the magnitude of hepatocyte apoptosis and independently predict the presence of NASH. Our aim was to validate the utility of this novel biomarker for NASH diagnosis. The study was an ancillary study of the NASH Clinical Research Network (NASH CRN). Our cohort consisted of 139 patients with biopsy proven NAFLD from eight centers across the United States who are participants of the CRN and 150 age-matched healthy controls. CK-18 fragments were measured using a specific immunoELISA. Histology was assessed centrally by study pathologists.CK-18 fragments were markedly increased in patients with NASH as compared to not NASH and borderline diagnosis (Median (Q25, Q75): 335 (196, 511), 194 (151, 270), 200 (148, 284), respectively; P < 0.001). Moreover, the odds of having fibrosis on liver biopsy increased with increasing plasma CK-18 fragment levels (P < 0.001). On multivariable regression analysis, CK-18 fragments remained an independent predictor of NASH after adjusting for variables associated with CK-18 fragments or NASH on the univariable analysis (fibrosis, ALT, AST, age, biopsy length). The area under the ROC curve for NASH diagnosis was estimated to be 0.83 (0.75, 0.91). Determination of CK-18 fragments in the blood predicts histological NASH and severity of disease in a large, diverse population of patients with biopsy-proven NAFLD, supporting the potential usefulness of this test in clinical practice.
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影响因子：
2.4
作者：
Poynard T;Ratziu V;Charlotte F;Messous D;Munteanu M;Imbert-Bismut F;Massard J;Bonyhay L;Tahiri M;Thabut D;Cadranel JF;Le Bail B;de Ledinghen V;LIDO Study Group;CYTOL study group
通讯作者：
CYTOL study group
DOI：
10.1124/jpet.103.060129
发表时间：
2004-03-01
影响因子：
3.5
作者：
Canbay, A;Feldstein, A;Gores, GJ
通讯作者：
Gores, GJ
影响因子：
2.8
作者：
Sookoian, Silvia;Castano, Gustavo;Jose Pirola, Carlos
通讯作者：
Jose Pirola, Carlos
影响因子：
29.4
作者：
Matteoni, CA;Younossi, ZM;McCullough, AJ
通讯作者：
McCullough, AJ
影响因子：
2.9
作者：
Janiec, DJ;Jacobson, ER;Blaszyk, H
通讯作者：
Blaszyk, H