Limited value of plasma cytokeratin-18 as a biomarker for NASH and fibrosis in patients with non-alcoholic fatty liver disease
Limited value of plasma cytokeratin-18 as a biomarker for NASH and fibrosis in patients with non-alcoholic fatty liver disease
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DOI：
10.1016/j.jhep.2013.07.042
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发表时间：
2014-01-01
影响因子：
25.7
通讯作者：
Tio, Fermin
中科院分区：
文献类型：
--
作者：
Cusi, Kenneth;Chang, Zhi;Tio, Fermin
背景和目的：肝活检是诊断和分期 NASH 的唯一可靠方法，但其侵入性限制了其使用。血浆 caspase 生成的细胞角蛋白 18 片段 (CK-18) 已被提议作为一种非侵入性替代方案。我们研究了其在大量多种族 NAFLD 人群中的临床价值，并检验了其与临床/代谢/组织学参数的关系。方法：424 名中年受试者，我们通过 MRS 测量了脂肪组织、肝脏和肌肉胰岛素抵抗 (IR)、肝脏脂肪 (n = 275) 和组织学 (n = 318)。结果：通过 MRS 测量，与非 NAFLD 患者相比，患有 NAFLD 的患者中位 CK-18 升高 (209 [IQR: 137-329] vs. 122 [IQR: 98-155] U/L) 或有 NASH 与无 NASH (232 [IQR: 151-387] vs. 170 [IQR: 135-234] U/L，均 p < 0.001)。血浆 CK-18 随着脂肪变性、炎症和纤维化的增加而显着升高，但疾病严重程度之间存在显着重叠。预测 NAFLD、NASH 或纤维化的 CK-18 AUROC 分别为 0.77 (95% CI = 0.71-0.84)、0.65 (95% CI = 0.59-0.71) 和 0.68 (95% CI = 0.61-0.75)。 NAFLD、NASH 和纤维化的总体敏感性/特异性分别为 63% (57-70%)/83% (69-92%)、58% (51-65%)/68% (59-76%) 和 54% (44-63%)/85% (75-92%)。 CK-18 与 ALT（r = 0.57，p < 0.0001）和脂肪组织 IR（FFA 的胰岛素抑制：r = -0.43；p < 0.001）相关性最强，与脂肪变性、小叶炎症和纤维化相关性较小（r = 0.28-0.34，所有 p < 0.001），但与气球样变、BMI、代谢综合征或T2DM. 结论：血浆 CK-18 对 NAFLD 和纤维化具有高度特异性，但其有限的敏感性使其不足以作为 NASH 分期的筛查测试。与其他生物标志物或临床/实验室测试结合作为诊断组是否可能被证明是有用的，需要进一步研究。 (C) 2013 年欧洲肝脏研究协会。由 Elsevier B.V 出版。保留所有权利。
Background & Aims: Liver biopsy is the only reliable way of diagnosing and staging NASH but its invasive nature limits its use. Plasma caspase-generated cytokeratin-18 fragments (CK-18) have been proposed as a non-invasive alternative. We studied its clinical value in a large multiethnic NAFLD population and examined its relationship to clinical/metabolic/histological parameters.Methods: 424 middle-aged subjects in whom we measured adipose tissue, liver and muscle insulin resistance (IR), liver fat by MRS (n = 275) and histology (n = 318).Results: Median CK-18 were elevated in patients with vs. without NAFLD by MRS (209 [IQR: 137-329] vs. 122 [IQR: 98-155] U/L) or with vs. without NASH (232 [IQR: 151-387] vs. 170 [IQR: 135-234] U/L, both p < 0.001). Plasma CK-18 raised significantly with any increase in steatosis, inflammation and fibrosis, but there was a significant overlap across disease severity. The CK-18 AUROC to predict NAFLD, NASH or fibrosis were 0.77 (95% CI = 0.71-0.84), 0.65 (95% CI = 0.59-0.71) and 0.68 (95% CI = 0.61-0.75), respectively. The overall sensitivity/specificity for NAFLD, NASH and fibrosis were 63% (57-70%)/83% (69-92%), 58% (51-65%)/68% (59-76%) and 54% (44-63%)/85% (75-92%), respectively. CK-18 correlated most strongly with ALT (r = 0.57, p < 0.0001) and adipose tissue IR (insulin-suppression of FFA: r = -0.43; p < 0.001), less with steatosis, lobular inflammation and fibrosis (r = 0.28-0.34, all p < 0.001), but not with ballooning, BMI, metabolic syndrome or T2DM.Conclusions: Plasma CK-18 has a high specificity for NAFLD and fibrosis, but its limited sensitivity makes it inadequate as a screening test for staging NASH. Whether combined as a diagnostic panel with other biomarkers or clinical/laboratory tests may prove useful requires further study. (C) 2013 European Association for the Study of the Liver. Published by Elsevier B. V. All rights reserved.