Ichikawa T, Miuma S, Yamashima M, Yamamichi S, Koike M, Nakano Y, Yajima H, Miyazaki O, Ikeda T, Okamura T, Komatsu N, Yoshino M, Miyaaki H. Cytokeratin 18 fragment is associated with steatosis-associated fibrosis estimator score and lipid in patients with steatotic liver disease. World J Hepatol 2025; 17(11): 110698 [DOI: 10.4254/wjh.v17.i11.110698]
Corresponding Author of This Article
Tatsuki Ichikawa, MD, Department of Gastroenterology, Nagasaki Harbor Medical Center, 1-7-1 Sakamoto, Nagasaki 850-8555, Japan. ichikawa@nagasaki-u.ac.jp
Research Domain of This Article
Gastroenterology & Hepatology
Article-Type of This Article
Case Control Study
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This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Nov 27, 2025 (publication date) through Dec 4, 2025
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Publication Name
World Journal of Hepatology
ISSN
1948-5182
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Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA
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Ichikawa T, Miuma S, Yamashima M, Yamamichi S, Koike M, Nakano Y, Yajima H, Miyazaki O, Ikeda T, Okamura T, Komatsu N, Yoshino M, Miyaaki H. Cytokeratin 18 fragment is associated with steatosis-associated fibrosis estimator score and lipid in patients with steatotic liver disease. World J Hepatol 2025; 17(11): 110698 [DOI: 10.4254/wjh.v17.i11.110698]
Tatsuki Ichikawa, Mio Yamashima, Shinobu Yamamichi, Makiko Koike, Yusuke Nakano, Hiruyuki Yajima, Osamu Miyazaki, Tomonari Ikeda, Takauma Okamura, Naohiro Komatsu, Miruki Yoshino, Department of Gastroenterology, Nagasaki Harbor Medical Center, Nagasaki 850-8555, Japan
Satoshi Miuma, Department of Gastroenterology and Hepatology, Nagasaki University, Nagasaki 852-8501, Japan
Hisamitsu Miyaaki, Department of Gastroenterology and Hepatology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki 852-8501, Japan
Author contributions: Ichikawa T wrote the manuscript and designed the study; Ichikawa T and Miuma S confirmed the authenticity of the raw data; Ichikawa T, Yamashima M, Yamamichi S, Koike M, Nakano Y, Yajima H, Miyazaki O, Ikeda T, Okamura T, Komatsu N, Yoshino M, and Miyaaki H collected the data; Nakao Y analyzed the data; All authors have read and approved the final manuscript.
Institutional review board statement: The protocol for this research project has been approved by a suitably constituted Ethics Committee of the Institution (Committee of Nagasaki Harbor Medical Center, No. H30-057) and it conforms to the provisions of the Declaration of Helsinki.
Informed consent statement: Informed consent was obtained from each patient included in the study and they were guaranteed the right to leave the study if desired (opt out).
Conflict-of-interest statement: The authors have no conflicts of interest to declare.
STROBE statement: The authors have read the STROBE Statement-checklist of items, and the manuscript was prepared and revised according to the STROBE Statement-checklist of items.
Data sharing statement: The data generated in the present study are not publicly available (compelling reason exists owing to which the data are not public), but may be requested from the corresponding author.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Tatsuki Ichikawa, MD, Department of Gastroenterology, Nagasaki Harbor Medical Center, 1-7-1 Sakamoto, Nagasaki 850-8555, Japan. ichikawa@nagasaki-u.ac.jp
Received: June 13, 2025 Revised: July 3, 2025 Accepted: September 25, 2025 Published online: November 27, 2025 Processing time: 167 Days and 23.1 Hours
Abstract
BACKGROUND
Serum cytokeratin 18 fragment (CK18F) has been developed as a new non-invasive test (NIT) for risk assessment of steatotic liver disease (SLD); however, there are few reports on its relationship with existing NITs and association with cardiometabolic risk factors (CMRFs).
AIM
To clarify the relationship among CK18F, NITs, and CMRF.
METHODS
We included 125 patients who were assessed for SLD and had CK18F measured in cross-sectional study. The fibrosis-4 index (FIB-4), steatosis-associated fibrosis estimator (SAFE) score, liver stiffness (LS), controlled attenuation parameter, and FibroScan-aspartate aminotransferase (FAST) score were compared with CK18F as existing NITs.
RESULTS
CK18F was associated with aspartate aminotransferase, alanine aminotransferase, and triglyceride (TG). FAST and SAFE score were associated with high CK18F (> 260 U/L), but not FIB-4 or LS. The cut-off values for TG and high-density lipoprotein (HDL) cholesterol used to determine high CK18F using receiver operating characteristics analysis were 126 mg/dL and 56 mg/dL respectively. High TG (> 126 mg/dL) and low HDL (< 56 mg/dL) were associated with high CK18F. The risk of high CK18F was higher when high TG and low HDL were combined than when each was present alone. CMRF was higher in the high CK18F group, but was not associated with CK18F levels. However, when the TG and HDL criteria for CMRF were replaced by TG > 126 mg/mL and HDL < 56 mg/dL, modified CMRF (mCMRF) was associated with CK18F levels, with a higher risk of high CK18F than CMRF.
CONCLUSION
CK18F is a new NIT associated with SAFE score and FAST. High TG, low HDL, and mCMRF are associated with high CK18F.
Core Tip: Serum cytokeratin 18 fragment (CK18F) has been developed as a new non-invasive test for risk assessment of steatotic liver disease (SLD). We included 125 patients who were assessed for SLD and had CK18F measured. Steatosis-associated fibrosis estimator (SAFE) score, liver stiffness (LS), and FibroScan-aspartate aminotransferase (FAST) score were compared with CK18F. CK18F was associated with aspartate aminotransferase, alanine aminotransferase, and triglycerides (TGs). FAST and SAFE score were associated with high CK18F (> 260 U/L), but not fibrosis-4 or LS. Risk of high CK18F was higher when high TG and low high-density lipoprotein were combined than when each was present alone.
