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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
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