Performance of cytokeratin-18 apoptotic fragment for the identification of hepatic fibrosis and inflammation in patients with chronic viral hepatitis: a meta-analysis

INTRODUCTION: The search for non-invasive tools aiming to assess liver fibrosis and inflammation, and able to replace liver biopsy, remains one of the most important unmet need in clinical practice. Although cytokeratin 18-Asp396 (CK18-Asp396) apoptotic fragment has been considered an important marker of hepatitis progression, until now, conflicting results have been reported. Therefore, we performed a meta-analysis to evaluate the diagnostic accuracy of CK18-Asp396 for the detection of fibrosis and inflammation in patients with chronic hepatitis C (CHC) and chronic hepatitis B (CHB) infection.EVIDENCE ACQUISITION: Through PubMed and Scopus databases, we identified published papers on the evaluation of the diagnostic performance of CK18-Asp396 for the discrimination of patients with significant fibrosis and inflammation. Statistical analysis was performed with MedCalc Software.EVIDENCE SYNTHESIS: A total of 11 studies (425 patients with CHC and 1012 patients with CHB infection) were included in the meta-analysis. The median cut-off value of CK18-Asp396 marker for the identification of significant fibrosis was higher compared to the median cut-off value for the discrimination of significant inflammation (294 U/L vs. 234 U/L, P=0.05). The weighted summary area under the curve (sAUC) of CK18-Asp396 for the detection of significant fibrosis and inflammation was 0.75 (95% confidence interval [CI]=0.66-0.83) and 0.75 (95% CI=0.70-0.79), respectively. No difference was observed between the diagnostic performance of CK18-Asp396 in identifying significant fibrosis and significant inflammation.CONCLUSIONS: The measurement of serum CK18-Asp396 showed a moderate diagnostic accuracy for the detection of both significant fibrosis and significant inflammation in patients with chronic viral hepatitis. Possibly, the combination of CK18-Asp396 with other biomarkers of disease severity may improve its diagnostic performance.