Non-invasive diagnosis of non-alcoholic steatohepatitis by combined serum biomarkers

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• 作者：Jiayun Shen¹ ; ² ; Henry Lik-Yuen Chan¹ ; ² ; Grace Lai-Hung Wong¹ ; ² ; Paul Cheung-Lung Choi³ ; Anthony Wing-Hung Chan³ ; Hoi-Yun Chan¹ ; ² ; Angel Mei-Ling Chim¹ ; ² ; David Ka-Wai Yeung⁴ ; Francis Ka-Leung Chan¹ ; ² ; Jean Woo¹ ; Jun Yu¹ ; ² ; Winnie Chiu-Wing Chu² ; ⁵ ; Vincent Wai-Sun Wong¹ ; ² ; ^{wongv@cuhk.edu.hk}
• 关键词：AFABP ; adipocyte fatty acid binding protein ; ALT ; alanine aminotransferase ; AUROC ; area under the receiver operating characteristic curve ; BMI ; body mass index ; CK-18 ; cytokeratin-18 fragments ; FGF21 ; fibroblast growth factor 21 ; LDL ; low density lipoprot
• 刊名：Journal of Hepatology
• 出版年：2012
• 期刊代码：162_01688278
• 类别：med
• 出版时间：June, 2012
• 卷：56
• 期：6
• 页码：1363-1370
• 文件大小：823 K

摘要

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class="h4">Background & Aims

The diagnosis of non-alcoholic fatty liver disease (NAFLD) and steatohepatitis (NASH) is limited by the need for liver biopsy. We aimed at testing the accuracy of cytokeratin-18 fragment (CK-18), adipocyte fatty acid binding protein (AFABP) and fibroblast growth factor 21 (FGF21) for the diagnosis of NAFLD and NASH.

class="h4">Methods

146 patients with biopsy-proven NAFLD and 74 age- and gender-matched healthy controls were included. Serum CK-18, AFABP and FGF21 levels were determined by enzyme-linked immunosorbent assay.

class="h4">Results

Serum CK-18, AFABP, and FGF21 increased in a stepwise fashion in control subjects (median 103 U/L, 15.4 ng/ml, and 104 pg/ml), patients with non-NASH NAFLD (263 U/L, 18.9 ng/ml, and 249 pg/ml) and NASH (418 U/L, 19.4 ng/ml, and 354 pg/ml) (p <0.001, 0.060, and 0.016, respectively). The area under receiver-operating characteristics curve to diagnose NAFLD and NASH was 0.91 and 0.70 for CK-18, 0.66 and 0.59 for AFABP, and 0.84 and 0.62 for FGF21. At cut-offs of 203 and 670 U/L, CK-18 had 71%negative predictive value (NPV) and 77%positive predictive value (PPV) to exclude and diagnose NASH. A 2-step approach measuring CK-18 followed by FGF21 further improved the NPV to 74%and PPV to 82%. In a validation cohort of 51 patients with paired liver biopsies, the NPV and PPV of the 2-step approach were 67%and 78%, respectively.

class="h4">Conclusions

CK-18 is the most accurate biomarker for NAFLD and NASH. A two-step approach using CK-18 and FGF21 further improves the accuracy in diagnosing NASH.