Serum YKL-40 Levels as a Non-invasive Potential Biomarker for Liver Fibrosis Patients: A Systematic Review and Meta-Analysis
Abstract
Background: This research’s comprehensive review and meta-analysis seek to offer additional non-invasive techniques for diagnosing and monitoring liver fibrosis, thereby serving as a dependable resource for clinical practice and scientific investigation.
Methods: To find pertinent research on the use of serum YKL-40 levels in liver fibrosis patients, databases including PubMed, Web of Science, WILEY ONLINE LIBRARY, Scopus, Embase, Cochrane Library, Science Direct, CNKI, Wanfang Data, VIP Information, and the China Biology Medicine Library System were searched. The search was conducted up to May 2024.
Results: In studies comparing serum YKL-40 levels in patients with hepatic fibrosis and controls, the overall combined difference was 1.37 (0.66, 2.08), with the Chinese subgroup showing high heterogeneity, while the Egyptian study did not show heterogeneity. A total of 17 studies, including 2554 patients, were included. The combined sensitivity for diagnosing advanced fibrosis and severe fibrosis was 0.80 and 0.78 respectively, with specificities of 0.88 and 0.82. The AUC for advanced fibrosis and severe fibrosis were 0.91 and 0.87 respectively.
Conclusion: Serum YKL-40 shows potential value in diagnosis of liver fibrosis, but further clinical research is needed to confirm and improve its utility.
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2. Del Turco S, De Simone P, Ghinolfi D, et al (2021). Comparison between galectin-3 and YKL-40 levels for the assessment of liver fibrosis in cirrhotic patients. Ar-ab J Gastroenterol, 22(3):187-92.
3. Ma B, Akosman B, Kamle S, et al (2021). CHI3L1 regulates PD-L1 and anti-CHI3L1-PD-1 antibody elicits synergistic antitumor responses. J Clin Invest, 131(21):e137750.
4. Connolly K, Lehoux M, O'Rourke R, et al (2023). Potential role of chitinase-3-like protein 1 (CHI3L1/YKL-40) in neuro-degeneration and Alzheimer's disease. Alzheimers Dement, 19(1):9-24.
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6. Man S, Deng Y, Ma Y, et al (2023). Preva-lence of Liver Steatosis and Fibrosis in the General Population and Various High-Risk Populations: A Nationwide Study With 5.7 Million Adults in China. Gastroenterology, 165(4):1025-40.
7. Moher D, Liberati A, Tetzlaff J, et al (2009). Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med, 6(7): e1000097.
8. Ho SY, Wang LC, Hsu CY, et al (2020). Metavir Fibrosis Stage in Hepatitis C-Related Hepatocellular Carcinoma and Association with Noninvasive Liver Re-serve Models. J Gastrointest Surg, 24(8):1860-2.
9. Whiting PF, Rutjes AW, Westwood ME, et al (2011). QUADAS-2: a revised tool for the quality assessment of diagnostic ac-curacy studies. Ann Intern Med, 155(8):529-36.
10. Bao J, Ouyang Y, Qiao L, et al (2022). Se-rum CHI3L1 as a Biomarker for Non-invasive Diagnosis of Liver Fibrosis. Discov Med, 33(168):41-9.
11. Zhang F, Han Y, Zheng L, et al (2023). As-sociation of Non-Invasive Markers with Significant Fibrosis in Patients with Nonalcoholic Fatty Liver Disease: A Cross-Sectional Study. Diabetes Metab Syndr Obes, 16:2255-68.
12. Li H, Yan T, Zhu Z, et al (2018). Diagnostic value of serum chitosanase 3-like pro-tein 1 in chronic liver disease with sig-nificant fibrosis and cirrhosis. Zhonghua Gan Zang Bing Za Zhi, 26(5):337-41.
13. Li Y, Li C, Zhang L, et al (2022). Serum CHI3L1 as a diagnostic marker and risk factor for liver fibrosis in HBeAg-negative chronic hepatitis B. Am J Transl Res, 14(6):4090-6.
14. Yan L, Deng Y, Zhou J, et al (2018). Serum YKL-40 as a biomarker for liver fibrosis in chronic hepatitis B patients with normal and mildly elevated ALT. Infec-tion, 46(3):385-93.
15. Jiang Z, Wang S, Jin J, et al (2020). The clin-ical significance of serum chitinase 3-like 1 in hepatitis B-related chronic liver diseases. J Clin Lab Anal, 34(5):e23200.
16. Jin X, Fu B, Wu ZJ, et al (2020). Serum chi-tinase-3-like protein 1 is a biomarker of liver fibrosis in patients with chronic hepatitis B in China. Hepatobiliary Pancre-at Dis Int, 19(4):384-9.
17. Huang H, Wu T, Mao J, et al (2015). CHI3L1 Is a Liver-Enriched, Noninvasive Bi-omarker That Can Be Used to Stage and Diagnose Substantial Hepatic Fibrosis. OMICS, 19(6):339-45.
18. Kumagai E, Mano Y, Yoshio S, et al (2016). Serum YKL-40 as a marker of liver fi-brosis in patients with non-alcoholic fat-ty liver disease. Sci Rep, 6:35282.
19. Schiavon LL, Narciso-Schiavon JL, Car-valho Filho RJ, et al (2008). Serum levels of YKL-40 and hyaluronic acid as non-invasive markers of liver fibrosis in haemodialysis patients with chronic hepatitis C virus infection. J Viral Hepat, 15(9):666-74.
20. Qiu H, Zhang X (2022). The Value of Se-rum CHI3L1 for the Diagnosis of Chronic Liver Diseases. Int J Gen Med, 15:5835-41.
21. Saitou Y, Shiraki K, Yamanaka Y, et al (2005). Noninvasive estimation of liver fibrosis and response to interferon therapy by a serum fibrogenesis marker, YKL-40, in patients with HCV-associated liver disease. World J Gastroenterol, 11(4):476-81.
22. Hu Z, Lu T (2024). Study on the effects and diagnostic value of serum CHI3L1, Fi-broTouch, APRI, and FIB-4 on liver fi-brosis in hepatitis B. Chinese Journal of In-tegrated Traditional and Western Medicine on Liver Diseases, 34(4):323-6.
23. Lin C, Yang F, Huang Q (2021). Compari-son of the diagnostic efficacy of CHI3L1 and GPR in patients with liver fibrosis. China Health Standard Manage-ment, 12(22):54-7.
24. Li Y, Hu W, Xu X, et al (2021). A noninva-sive diagnostic model of chitosanase 3-like protein 1 in HBeAg-negative chron-ic hepatitis B liver fibrosis. Chinese Jour-nal of Health Laboratory Technology, 31(12):1460-3.
25. Huang Q, Wu J, Huang C, et al (2021). A noninvasive diagnostic model for signif-icant liver fibrosis in patients with chronic hepatitis B based on CHI3L1 and routine clinical indicators. Ann Pal-liat Med, 10(5):5509-19.
26. Toson EA, Shiha GE, El-Saied E SH, et al (2016). Can YKL-40 improve the diag-nostic power of non-invasive fibrogenic staging in chronic hepatitis B virus in-fected patients?. Eur J Pharm Med Res, 3(11):70-78.
27. Roehlen N, Crouchet E, Baumert T F (2020). Liver Fibrosis: Mechanistic Con-cepts and Therapeutic Perspectives. Cells, 9(4): 875.
28. Hammerich L, Tacke F (2023). Hepatic in-flammatory responses in liver fibrosis. Nat Rev Gastroenterol Hepatol, 20(10):633-46.
29. Fontana RJ, Litman HJ, Dienstag JL, et al (2012). YKL-40 genetic polymorphisms and the risk of liver disease progression in patients with advanced fibrosis due to chronic hepatitis C. Liver Int, 32(4):665-74.
30. Pungpapong S, Nunes DP, Krishna M, et al (2008). Serum fibrosis markers can pre-dict rapid fibrosis progression after liv-er transplantation for hepatitis C. Liver Transpl, 14(9):1294-302.
31. Cai J, Lyu X, Huang P, et al (2022). In-creased Levels of CHI3L1 and HA Are Associated With Higher Occurrence of Liver Damage in Patients With Obstruc-tive Sleep Apnea. Front Med (Lausanne), 9:854570.
32. Temel Yüksel İ, Aslan Çetin B, Köroğlu N, et al (2019). Inflammatory marker YKL-40 levels in intrahepatic cholestasis of pregnancy. Gynecol Endocrinol, 35(7):635-7.
33. Rivas-Alarcón AA, Gómez-Gómez Y, Or-ganista-Nava J, et al (2021). Plasma levels of YKL-40 as a prognostic factor in childhood acute lymphoblastic leuke-mia. Mol Clin Oncol, 15(2):168.
34. Jing-Lun Z, Shuang C, Li-Mei Z, et al (2023). YKL-40 promotes chemokine expres-sion following drug-induced liver injury via TF-PAR1 pathway in mice. Front Pharmacol, 14:1205062.
35. Huang X, Zhuang J, Yang Y, et al (2022). Diagnostic Value of Serum Chitinase-3-Like Protein 1 for Liver Fibrosis: A Me-ta-analysis. Biomed Res Int, 2022:3227957.
2. Del Turco S, De Simone P, Ghinolfi D, et al (2021). Comparison between galectin-3 and YKL-40 levels for the assessment of liver fibrosis in cirrhotic patients. Ar-ab J Gastroenterol, 22(3):187-92.
3. Ma B, Akosman B, Kamle S, et al (2021). CHI3L1 regulates PD-L1 and anti-CHI3L1-PD-1 antibody elicits synergistic antitumor responses. J Clin Invest, 131(21):e137750.
4. Connolly K, Lehoux M, O'Rourke R, et al (2023). Potential role of chitinase-3-like protein 1 (CHI3L1/YKL-40) in neuro-degeneration and Alzheimer's disease. Alzheimers Dement, 19(1):9-24.
5. Jophlin LL, Singal AK, Bataller R, et al (2024). ACG Clinical Guideline: Alco-hol-Associated Liver Disease. Am J Gas-troenterol, 119(1):30-54.
6. Man S, Deng Y, Ma Y, et al (2023). Preva-lence of Liver Steatosis and Fibrosis in the General Population and Various High-Risk Populations: A Nationwide Study With 5.7 Million Adults in China. Gastroenterology, 165(4):1025-40.
7. Moher D, Liberati A, Tetzlaff J, et al (2009). Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med, 6(7): e1000097.
8. Ho SY, Wang LC, Hsu CY, et al (2020). Metavir Fibrosis Stage in Hepatitis C-Related Hepatocellular Carcinoma and Association with Noninvasive Liver Re-serve Models. J Gastrointest Surg, 24(8):1860-2.
9. Whiting PF, Rutjes AW, Westwood ME, et al (2011). QUADAS-2: a revised tool for the quality assessment of diagnostic ac-curacy studies. Ann Intern Med, 155(8):529-36.
10. Bao J, Ouyang Y, Qiao L, et al (2022). Se-rum CHI3L1 as a Biomarker for Non-invasive Diagnosis of Liver Fibrosis. Discov Med, 33(168):41-9.
11. Zhang F, Han Y, Zheng L, et al (2023). As-sociation of Non-Invasive Markers with Significant Fibrosis in Patients with Nonalcoholic Fatty Liver Disease: A Cross-Sectional Study. Diabetes Metab Syndr Obes, 16:2255-68.
12. Li H, Yan T, Zhu Z, et al (2018). Diagnostic value of serum chitosanase 3-like pro-tein 1 in chronic liver disease with sig-nificant fibrosis and cirrhosis. Zhonghua Gan Zang Bing Za Zhi, 26(5):337-41.
13. Li Y, Li C, Zhang L, et al (2022). Serum CHI3L1 as a diagnostic marker and risk factor for liver fibrosis in HBeAg-negative chronic hepatitis B. Am J Transl Res, 14(6):4090-6.
14. Yan L, Deng Y, Zhou J, et al (2018). Serum YKL-40 as a biomarker for liver fibrosis in chronic hepatitis B patients with normal and mildly elevated ALT. Infec-tion, 46(3):385-93.
15. Jiang Z, Wang S, Jin J, et al (2020). The clin-ical significance of serum chitinase 3-like 1 in hepatitis B-related chronic liver diseases. J Clin Lab Anal, 34(5):e23200.
16. Jin X, Fu B, Wu ZJ, et al (2020). Serum chi-tinase-3-like protein 1 is a biomarker of liver fibrosis in patients with chronic hepatitis B in China. Hepatobiliary Pancre-at Dis Int, 19(4):384-9.
17. Huang H, Wu T, Mao J, et al (2015). CHI3L1 Is a Liver-Enriched, Noninvasive Bi-omarker That Can Be Used to Stage and Diagnose Substantial Hepatic Fibrosis. OMICS, 19(6):339-45.
18. Kumagai E, Mano Y, Yoshio S, et al (2016). Serum YKL-40 as a marker of liver fi-brosis in patients with non-alcoholic fat-ty liver disease. Sci Rep, 6:35282.
19. Schiavon LL, Narciso-Schiavon JL, Car-valho Filho RJ, et al (2008). Serum levels of YKL-40 and hyaluronic acid as non-invasive markers of liver fibrosis in haemodialysis patients with chronic hepatitis C virus infection. J Viral Hepat, 15(9):666-74.
20. Qiu H, Zhang X (2022). The Value of Se-rum CHI3L1 for the Diagnosis of Chronic Liver Diseases. Int J Gen Med, 15:5835-41.
21. Saitou Y, Shiraki K, Yamanaka Y, et al (2005). Noninvasive estimation of liver fibrosis and response to interferon therapy by a serum fibrogenesis marker, YKL-40, in patients with HCV-associated liver disease. World J Gastroenterol, 11(4):476-81.
22. Hu Z, Lu T (2024). Study on the effects and diagnostic value of serum CHI3L1, Fi-broTouch, APRI, and FIB-4 on liver fi-brosis in hepatitis B. Chinese Journal of In-tegrated Traditional and Western Medicine on Liver Diseases, 34(4):323-6.
23. Lin C, Yang F, Huang Q (2021). Compari-son of the diagnostic efficacy of CHI3L1 and GPR in patients with liver fibrosis. China Health Standard Manage-ment, 12(22):54-7.
24. Li Y, Hu W, Xu X, et al (2021). A noninva-sive diagnostic model of chitosanase 3-like protein 1 in HBeAg-negative chron-ic hepatitis B liver fibrosis. Chinese Jour-nal of Health Laboratory Technology, 31(12):1460-3.
25. Huang Q, Wu J, Huang C, et al (2021). A noninvasive diagnostic model for signif-icant liver fibrosis in patients with chronic hepatitis B based on CHI3L1 and routine clinical indicators. Ann Pal-liat Med, 10(5):5509-19.
26. Toson EA, Shiha GE, El-Saied E SH, et al (2016). Can YKL-40 improve the diag-nostic power of non-invasive fibrogenic staging in chronic hepatitis B virus in-fected patients?. Eur J Pharm Med Res, 3(11):70-78.
27. Roehlen N, Crouchet E, Baumert T F (2020). Liver Fibrosis: Mechanistic Con-cepts and Therapeutic Perspectives. Cells, 9(4): 875.
28. Hammerich L, Tacke F (2023). Hepatic in-flammatory responses in liver fibrosis. Nat Rev Gastroenterol Hepatol, 20(10):633-46.
29. Fontana RJ, Litman HJ, Dienstag JL, et al (2012). YKL-40 genetic polymorphisms and the risk of liver disease progression in patients with advanced fibrosis due to chronic hepatitis C. Liver Int, 32(4):665-74.
30. Pungpapong S, Nunes DP, Krishna M, et al (2008). Serum fibrosis markers can pre-dict rapid fibrosis progression after liv-er transplantation for hepatitis C. Liver Transpl, 14(9):1294-302.
31. Cai J, Lyu X, Huang P, et al (2022). In-creased Levels of CHI3L1 and HA Are Associated With Higher Occurrence of Liver Damage in Patients With Obstruc-tive Sleep Apnea. Front Med (Lausanne), 9:854570.
32. Temel Yüksel İ, Aslan Çetin B, Köroğlu N, et al (2019). Inflammatory marker YKL-40 levels in intrahepatic cholestasis of pregnancy. Gynecol Endocrinol, 35(7):635-7.
33. Rivas-Alarcón AA, Gómez-Gómez Y, Or-ganista-Nava J, et al (2021). Plasma levels of YKL-40 as a prognostic factor in childhood acute lymphoblastic leuke-mia. Mol Clin Oncol, 15(2):168.
34. Jing-Lun Z, Shuang C, Li-Mei Z, et al (2023). YKL-40 promotes chemokine expres-sion following drug-induced liver injury via TF-PAR1 pathway in mice. Front Pharmacol, 14:1205062.
35. Huang X, Zhuang J, Yang Y, et al (2022). Diagnostic Value of Serum Chitinase-3-Like Protein 1 for Liver Fibrosis: A Me-ta-analysis. Biomed Res Int, 2022:3227957.
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| Issue | Vol 54 No 5 (2025) | |
| Section | Review Article(s) | |
| DOI | https://doi.org/10.18502/ijph.v54i5.18629 | |
| Keywords | ||
| Liver fibrosis Biomarkers Meta-analysis | ||
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How to Cite
1.
Li H, Xu X, Yan T. Serum YKL-40 Levels as a Non-invasive Potential Biomarker for Liver Fibrosis Patients: A Systematic Review and Meta-Analysis. Iran J Public Health. 2025;54(5):939-950.
