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Meta-Analysis
. 2017:2017:9729107.
doi: 10.1155/2017/9729107. Epub 2017 Feb 23.

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

Lei He  1 , Linfeng Deng  1 , Quan Zhang  2 , Jianli Guo  3 , Jinan Zhou  1 , Wenjian Song  4 , Fahu Yuan  4
Affiliations
Meta-Analysis

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

Lei He et al. Biomed Res Int. 2017.

Abstract

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.

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Conflict of interest statement

The authors declare no competing financial interests.

Figures

Figure 1
Figure 1
Flow diagram demonstrating literature search and selection of studies of CK-18, FGF-21, and combined biomarker panel for diagnosing NASH.
Figure 2
Figure 2
Combined DS and DOR of CK-18, M30 fragment. DS, diagnostic score. DOR, diagnostic odds ratio. CI, confidence interval.
Figure 3
Figure 3
Summary receiver's operative characteristics of CK-18, M30 fragment. AUC, area under the curve. SENS, sensitivity. SPEC, specificity.
Figure 4
Figure 4
Combined DS, DOR (a), and sensitivity and specificity (b) of FGF-21. DS, diagnostic score. DOR, diagnostic odds ratio. CI, confidence interval.
Figure 5
Figure 5
Summary receiver's operative characteristics of CBP. AUC, area under the curve. SENS, sensitivity. SPEC, specificity.
Figure 6
Figure 6
Pooled DS, DOR (a), and sensitivity and specificity (b) of CBP. DS, diagnostic score. DOR, diagnostic odds ratio. CI, confidence interval.
See this image and copyright information in PMC

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References

    1. Marchesini G., Bugianesi E., Forlani G., et al. Nonalcoholic fatty liver, steatohepatitis, and the metabolic syndrome. Hepatology. 2003;37(4):917–923. doi: 10.1053/jhep.2003.50161. - DOI - PubMed
    1. Fabbrini E., Sullivan S., Klein S. Obesity and nonalcoholic fatty liver disease: biochemical, metabolic, and clinical implications. Hepatology. 2010;51(2):679–689. doi: 10.1002/hep.23280. - DOI - PMC - PubMed
    1. Chitturi S., Farrell G. C., George J. Non-alcoholic steatohepatitis in the Asia-Pacific region: future shock? Journal of Gastroenterology and Hepatology (Australia) 2004;19(4):368–374. doi: 10.1111/j.1440-1746.2003.03252.x. - DOI - PubMed
    1. Michelotti G. A., Machado M. V., Diehl A. M. NAFLD, NASH and liver cancer. Nature Reviews Gastroenterology & Hepatology. 2013;10(11):656–665. doi: 10.1038/nrgastro.2013.183. - DOI - PubMed
    1. Ascha M. S., Hanouneh I. A., Lopez R., Tamimi T. A.-R., Feldstein A. F., Zein N. N. The incidence and risk factors of hepatocellular carcinoma in patients with nonalcoholic steatohepatitis. Hepatology. 2010;51(6):1972–1978. doi: 10.1002/hep.23527. - DOI - PubMed