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Meta-Analysis
. 2025 Apr;39(8):e70034.
doi: 10.1002/jcla.70034. Epub 2025 Apr 9.

Diagnostic Value of Serum Cytokeratin 18 for the Staging of Liver Inflammation and Fibrosis: A Meta-Analysis

Jinwen Chen  1 , Jian Hu  1 , Jialin Zhuang  2 , Zhong Li  3 , Se Peng  1 , Xiaoting Huang  4 , Jialing Zhuang  1
Affiliations
Meta-Analysis

Diagnostic Value of Serum Cytokeratin 18 for the Staging of Liver Inflammation and Fibrosis: A Meta-Analysis

Jinwen Chen et al. J Clin Lab Anal. 2025 Apr.

Abstract

Background and aims: Accurate assessment of liver inflammation and fibrosis is of vital importance in the clinical management of patients with liver diseases. Our aim is to conduct a meta-analysis to evaluate the diagnostic accuracy of serum cytokeratin 18 (CK18) for staging of liver inflammation and fibrosis against a liver biopsy in adults.

Methods: We systematically searched articles from eight electronic databases. Two authors independently selected included studies, extracted data, and assessed quality. In our meta-analysis, we used the random-effects meta-analysis model. Publication bias, sensitivity analysis, heterogeneity analysis, and post-test probability were used in this meta study.

Results: A total of 20 studies with 2235 patients were initially found by the search strategies. The pooled sensitivity, specificity, and area under the curve (AUC) of the summary receiver operating characteristic curve were 0.56, 0.81, and 0.810 for significant fibrosis; 0.64, 0.76, and 0.785 for advanced fibrosis; 0.53, 0.76, and 0.830 for cirrhosis; and 0.68, 0.73, and 0.786 for significant inflammation, respectively. High heterogeneity was observed in our meta-analysis because of factors such as the proportion of males, total number, and antigens of CK-18.

Conclusion: Serum CK18 had moderate diagnostic value (AUC > 0.7) in different stages of liver fibrosis and significant inflammation, offering a complementary approach to other non-invasive indicators such as serological biomarkers and imaging techniques. Future research should focus on elucidating the role of CK18 in the occurrence and progression of hepatitis and liver fibrosis, particularly in liver diseases with diverse etiologies.

Keywords: cytokeratin 18; diagnostic; fibrosis; inflammation; liver biopsy.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

FIGURE 1
FIGURE 1
Preferred Reporting Items for Systematic Reviews and Meta‐Analyses flow chart of study selection.
FIGURE 2
FIGURE 2
The pooled diagnostic accuracy of serum CK18 assessing fibrosis stages. (A–C) The pooled diagnostic accuracy of serum CK18 for significant fibrosis (F ≥ 2); (D–F) The pooled diagnostic accuracy of serum CK18 for advanced fibrosis (F ≥ 3); (G–I) The pooled diagnostic accuracy of serum CK18 for cirrhosis (F4). (A, D, G) Forest plot for the sensitivity. (B, E, H) Forest plot for the specificity. (C, F, I) The summary receiver operator characteristic curve. CI, confidence interval; AUC, area under the curve; SROC, summary receiver operating characteristic.
FIGURE 3
FIGURE 3
The diagnostic accuracy of serum CK18 for significant liver inflammation. (A) Forest plot for the sensitivity; (B) Forest plot for the specificity; (C) The summary receiver operator characteristic curve. CI, confidence interval; AUC, area under the curve; SROC, summary receiver operating characteristic.
See this image and copyright information in PMC

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