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BioMed Research International
Volume 2017 (2017), Article ID 9729107, 12 pages
Review Article

Diagnostic Value of CK-18, FGF-21, and Related Biomarker Panel in Nonalcoholic Fatty Liver Disease: A Systematic Review and Meta-Analysis

1Department of Blood Transfusion, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
2Department of Laboratory Medicine, Hubei Provincial Hospital of Integrated Chinese & Western Medicine, Wuhan, China
3Department of Biochemistry and Molecular Biology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
4School of Medicine, Jianghan University, Wuhan, China

Correspondence should be addressed to Fahu Yuan

Received 19 November 2016; Accepted 19 January 2017; Published 23 February 2017

Academic Editor: Kusum Kharbanda

Copyright © 2017 Lei He et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Liver biopsy still remains the gold standard for diagnosing nonalcoholic steatohepatitis (NASH), but with limitations. There is an urgent need to develop noninvasive tests that accurately distinguish NASH from simple steatosis. The purpose of this meta-analysis was to evaluate the diagnostic value of serum biomarkers including cytokeratin 18 (CK-18), fibroblast growth factor 21 (FGF-21), and combined biomarker panel (CBP) in the diagnosis of NAFLD, especially NASH. A total of 25 studies met the inclusion criteria. Pooled sensitivity and specificity values for chosen serum markers for diagnosing NASH are as follows: CK-18 (M30), 0.75 and 0.77; CK-18 (M65), 0.71 and 0.77; FGF-21, 0.62 and 0.78; and CBP, 0.92 and 0.85. CBP demonstrated better accuracy with higher sensitivity and specificity than those tested individually. Furthermore, the AUROC of CBP was 0.94 (95% CI, 0.92–0.96), compared to CK-18 or FGF-21 assay, which showed the most significant ability to distinguish NASH from simple steatosis. The results suggest that increased circulating CK-18 and FGF-21 are associated with NASH and may be used for initial assessment, but not enough. Importantly, CBP is potentially used as accurate diagnostic tools for NASH. Further prospective designed studies are warranted to confirm our findings.