Cytokeratin 18 as an emerging biomarker for the non-invasive diagnosis of non-alcoholic steatohepatitis
DOI:
https://doi.org/10.62305/biosana.v5i5.840Keywords:
Non-alcoholic Fatty Liver Disease, Nonalcoholic Steatohepatitis, Keratin-18, BiomarkersAbstract
Cytokeratin 18 (CK-18) is a cytoskeletal protein present in hepatocytes, whose study has gained clinical relevance as a potential non-invasive biomarker for the diagnosis of non-alcoholic steatohepatitis (NASH). A literature review was conducted with the objective of analyzing the diagnostic value of cytokeratin 18 as a non-invasive biomarker for non-alcoholic steatohepatitis. The variety of studies reviewed shows that CK-18 has diagnostic utility for detecting NASH when analyzed in conjunction with other inflammatory biomarkers; however, standardized reference values for CK-18 are lacking, which makes its clinical interpretation challenging. It is concluded that CK-18 acquires greater diagnostic value when used as part of non-invasive panels, contributing to a more accurate and early diagnosis of non-alcoholic steatohepatitis.
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Zhang H, Rios RS, Boursier J, Anty R, Chan WK, George J, et al. Hepatocyte apoptosis fragment product cytokeratin-18 M30 level and non-Alcoholic steatohepatitis risk diagnosis: An international registry study. Chin Med J (Engl) [Internet]. 2023 Feb 5 [cited 2025 Sep 1];136(3):341–50. Available from: https://pubmed.ncbi.nlm.nih.gov/36848175/
Alaa H, Mahmoud A, Dalia S, Somaia SE, Sheren Y, Esmat M. Value of Cytokeratin-18 as a non-invasive diagnostic biomarker of nonalcoholic steatohepatitis (NASH). Medical Journal of Viral Hepatitis [Internet]. 2019 Apr 1 [cited 2025 Sep 1];3.2(2):65–74. Available from: https://mjvh.journals.ekb.eg/article_55732.html
Rojas YAO, Cuellar CLV, Barrón KMA, Arab JP, Miranda AL. Non-alcoholic fatty liver disease prevalence in Latin America: A systematic review and meta-analysis. Ann Hepatol [Internet]. 2022 Nov 1 [cited 2025 Sep 1];27(6). Available from: https://pubmed.ncbi.nlm.nih.gov/35427804/
Cabrera D, Moncayo-Rizzo J, Cevallos K, Alvarado-Villa G. Waist Circumference as a Risk Factor for Non-Alcoholic Fatty Liver Disease in Older Adults in Guayaquil, Ecuador. Geriatrics 2023, Vol 8, Page 42 [Internet]. 2023 Apr 14 [cited 2025 Sep 10];8(2):42. Available from: https://www.mdpi.com/2308-3417/8/2/42/htm
Pouwels S, Sakran N, Graham Y, Leal A, Pintar T, Yang W, et al. Non-alcoholic fatty liver disease (NAFLD): a review of pathophysiology, clinical management and effects of weight loss. BMC Endocr Disord [Internet]. 2022 Dec 1 [cited 2025 Sep 1];22(1):1–9. Available from: https://bmcendocrdisord.biomedcentral.com/articles/10.1186/s12902-022-00980-1
Rinella ME, Lazarus J V, Ratziu V, Francque SM, Sanyal AJ, Kanwal F, et al. A multisociety Delphi consensus statement on new fatty liver disease nomenclature. J Hepatol [Internet]. 2023 [cited 2025 Oct 10];79:1542–56. Available from: https://doi.org/10.1016/j.jhep.2023.06.003
Al-Beltaji Ali, Al-qatati Abeer, Alzaharna Mazen. View of Serum Cytokeratin-18 as a Non-invasive Biomarker and its Association with Biochemical Parameters in the Diagnosis of Non-alcoholic Fatty Liver Disease [Internet]. 2024 [cited 2025 Sep 8]. Available from: https://jjournals.ju.edu.jo/index.php/JMJ/article/view/245/1062
Cañarte Murillo JR, López López LY, Lascano Garcés MO, Guiracocha Franco KN, Morales Toapanta MS. Insuficiencia hepática relacionada con la esteatosis en jóvenes de Ecuador. Arandu UTIC. 2024 Oct 1;11(2):660–77.
Coello Viñán JE, Sánchez-De la Torre ME, Coronel Parra AM, Caicedo Mosquera DS, Sócola Macas RY, Escobar Bautista AR, et al. Factores asociados a esteatosis hepática no alcohólica en pacientes del área rural del cantón Chambo. Revista Eugenio Espejo [Internet]. 2022 Jan 11 [cited 2025 Sep 1];16(1):39–49. Available from: http://scielo.senescyt.gob.ec/scielo.php?script=sci_arttext&pid=S2661-67422022000100039&lng=es&nrm=iso&tlng=es
López-Sánchez GN, Montalvo-Javé E, Domínguez-Perez M, Antuna-Puente B, Beltrán-Anaya FO, Hidalgo-Miranda A, et al. Hepatic mir-122-3p, mir-140-5p and mir-148b-5p expressions are correlated with cytokeratin-18 serum levels in MAFLD. Ann Hepatol [Internet]. 2022 Nov 1 [cited 2025 Oct 10];27(6):100756. Available from: https://www.sciencedirect.com/science/article/pii/S1665268122000989?via%3Dihub
Kleiner DE, Brunt EM, Van Natta M, Behling C, Contos MJ, Cummings OW, et al. Design and validation of a histological scoring system for nonalcoholic fatty liver disease. Hepatology [Internet]. 2005 Jun 1 [cited 2025 Sep 10];41(6):1313–21. Available from: https://onlinelibrary.wiley.com/doi/pdf/10.1002/hep.20701
Kawanaka M, Kamada Y, Takahashi H, Iwaki M, Nishino K, Zhao W, et al. Serum Cytokeratin 18 Fragment Is an Indicator for Treating Metabolic Dysfunction-Associated Steatotic Liver Disease. Gastro Hep Advances [Internet]. 2024 Jan 1 [cited 2025 Oct 9];3(8):1120–8. Available from: https://pubmed.ncbi.nlm.nih.gov/39533978/
Liu Z, Ren Q, Mu H, Zeng Y, An Z, He H. Preliminary study on the diagnostic value of LEAP-2 and CK18 in biopsy-proven MAFLD. BMC Gastroenterol [Internet]. 2024 Dec 1 [cited 2025 Oct 10];24(1):1–10. Available from: https://bmcgastroenterol.biomedcentral.com/articles/10.1186/s12876-024-03258-z
Pagano S, Bakker SJL, Juillard C, Dullaart RPF, Vuilleumier N. Serum Level of Cytokeratin 18 (M65) as a Prognostic Marker of High Cardiovascular Disease Risk in Individuals with Non-Alcoholic Fatty Liver Disease. 2023 [cited 2025 Oct 8]; Available from: https://doi.org/10.3390/biom13071128
de Alteriis G, Pugliese G, Di Sarno A, Muscogiuri G, Barrea L, Cossiga V, et al. Visceral Obesity and Cytokeratin-18 Antigens as Early Biomarkers of Liver Damage. Int J Mol Sci [Internet]. 2023 Jul 1 [cited 2025 Oct 10];24(13):10885. Available from: https://www.mdpi.com/1422-0067/24/13/10885/htm
Lee J, Vali Y, Boursier J, Duffin K, Verheij J, Julia Brosnan M, et al. Accuracy of cytokeratin 18 (M30 and M65) in detecting non-alcoholic steatohepatitis and fibrosis: A systematic review and meta-analysis. PLoS One [Internet]. 2020 Sep 1 [cited 2025 Sep 20];15(9):e0238717. Available from: https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0238717
Eguchi A, Iwasa M, Yamada M, Tamai Y, Shigefuku R, Hasegawa H, et al. A new detection system for serum fragmented cytokeratin 18 as a biomarker reflecting histologic activities of human nonalcoholic steatohepatitis. Hepatol Commun [Internet]. 2022 Aug 1 [cited 2025 Sep 21];6(8):1987–99. Available from: https://pubmed.ncbi.nlm.nih.gov/35485207/
Choi SJ, Yoon S, Kim KK, Kim D, Lee HE, Kim KG, et al. A Composite Blood Biomarker Including AKR1B10 and Cytokeratin 18 for Progressive Types of Nonalcoholic Fatty Liver Disease. Diabetes Metab J [Internet]. 2024 Jul 1 [cited 2025 Sep 22];48(4):740–51. Available from: http://e-dmj.org/journal/view.php?doi=10.4093/dmj.2023.0189
Zheng KI, Liu WY, Pan XY, Ma HL, Zhu PW, Wu XX, et al. Combined and sequential non-invasive approach to diagnosing non-alcoholic steatohepatitis in patients with non-alcoholic fatty liver disease and persistently normal alanine aminotransferase levels. BMJ Open Diabetes Res Care [Internet]. 2020 Mar 4 [cited 2025 Sep 24];8(1). Available from: https://pubmed.ncbi.nlm.nih.gov/32139603/
Zhang X, Zheng MH, Liu D, Lin Y, Song SJ, Chu ESH, et al. A blood-based biomarker panel for non-invasive diagnosis of metabolic dysfunction-associated steatohepatitis. Cell Metab [Internet]. 2025 Jan 7 [cited 2025 Sep 22];37(1):59-68.e3. Available from: https://pubmed.ncbi.nlm.nih.gov/39500327/
Alhinai A, Qayyum-Khan A, Zhang X, Samaha P, Metrakos P, Deschenes M, et al. Non-alcoholic steatohepatitis in liver transplant recipients diagnosed by serum cytokeratin 18 and transient elastography: A prospective study. World J Hepatol [Internet]. 2021 Dec 27 [cited 2025 Sep 22];13(12):2179–91. Available from: http://www.ncbi.nlm.nih.gov/pubmed/35070018
Karlas T, Petroff D, Garnov N, Böhm S, Tenckhoff H, Wittekind C, et al. Non-Invasive Assessment of Hepatic Steatosis in Patients with NAFLD Using Controlled Attenuation Parameter and 1H-MR Spectroscopy. PLoS One [Internet]. 2014 Mar 17 [cited 2025 Nov 6];9(3):e91987. Available from: https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0091987
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