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Serum levels of caspase-cleaved cytokeratin 18 (CK18-Asp396) predict severity of liver disease in chronic hepatitis B

Authors Li J, Verhaar AP, Pan Q, de Knegt RJ, Peppelenbosch MP

Received 24 February 2017

Accepted for publication 26 May 2017

Published 11 August 2017 Volume 2017:10 Pages 203—209

DOI https://doi.org/10.2147/CEG.S135526

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Amy Norman

Peer reviewer comments 2

Editor who approved publication: Professor Andreas M Kaiser


Juan Li, Auke P Verhaar, Qiuwei Pan, Robert Jacobus de Knegt, Maikel P Peppelenbosch

Erasmus MC Cancer Institute, Erasmus MC - University Medical Center Rotterdam, Rotterdam, the Netherlands

Background and aim:
Caspase-cleaved cytokeratin 18 (CK18-Asp396) is a potential clinically useful biomarker in liver disease as it is released from hepatocytes during apoptosis. In this study, we investigated serum CK18-Asp396 levels in chronic hepatitis B (CHB).
Patients and methods: Overall, 163 patients with CHB were included. Serum CK18‑Asp396 levels were determined by enzyme-linked immunosorbent assay (ELISA), and results were related to steatosis grade, histological activity index, inflammation score, and METAVIR fibrosis grade as well as to viral load, serum levels of liver enzymes, and albumin. Receiver operating characteristic analysis was used to evaluate the diagnostic performance of serum CK18-Asp396 levels for assessing disease activity.
Results: A higher level of serum CK 18 concentrations was found in patients with significant inflammation vs no significant inflammation (378.5 [interquartile range {IQR}: 173.2–629.6] vs 137.3 [87.5–197.7], P < 0.05; approximately threefold increase) and in patients with significant fibrosis vs no significant fibrosis (177.8 [IQR: 120.8–519.1] vs 142.7 [IQR: 88.8–214.4], P < 0.05; 1.25-fold increase). There was no differential CK 18 level by degree of steatosis. CK 18 was an independent predictor of significant inflammation with an 82% specificity and a 94% negative predictive value. We found the strongest correlation of CK 18 with alanine aminotransferase and aspartate aminotransferase (both r = 0.52; P < 0.001), but less with albumin (r = -0.24; P < 0.05) and viral load (log) (r = 0.19; P < 0.05).
Conclusion:
CHB appears to be accompanied by continuous high levels of hepatocyte apoptosis as judged from serum CK 18, suggesting that elimination of the infected compartment constitutes a defensive strategy against disease. Accordingly, CK 18 works as an independent predictor of significant inflammation with a high specificity.

Keywords: CHB, CK 18, apoptosis, steatosis, inflammation

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