Chitinase-3-like protein 1 as a predictor for the progression or regression of liver fibrosis

Abstract

Liver fibrosis is a wound-healing response of liver cells to chronic injuries caused by viral infections, including hepatitis B virus (HBV), hepatitis C virus (HCV), toxins, and alcohol abuse. The ability to stage diseases for treatment naïve patients to initiate proper medical procedures and predict the clinical causes of the disease or the treatment response is important given the increased prevalence of liver fibrosis caused by HBV, HCV and fatty liver diseases. CHI3L1 (chitinase-3-like protein 1, also known as YKL-40), which belongs to the chitinase family but lacks chitinolytic activity and is highly expressed in the liver, seems to fulfill this role. CHI3L1 is a non-invasive staging marker for liver fibrosis caused by HBV, HCV and non-alcoholic fatty liver disease as well as a predictor of the clinical causes and fibrotic changes after treatments. CHI3L1 predicts histological progression of liver fibrosis and fibrosis progression rate (fibrosis unit/year), rapid fibrosis progression after liver transplantation and response to interferon and recent direct acting antiviral therapy in chronic HCV patients. CHI3L1 also predicts response to antiviral therapy in chronic HBV patients.

Keywords

CHI3L1 / liver fibrosis / progression / regression / hepatitis B virus / hepatitis C virus / treatment response

References

[1] Pellicoro A,Iredale JP.Liver fibrosis and repair: immune regulation of wound healing in a solid organ.Nat Rev Immunol2014;14:181-94

[2] Liao B,Lin S,Yi J,Huang Z,Zhang F.Significant fibrosis is not rare in Chinese chronic hepatitis B patients with persistent normal ALT.PLoS One2013;8:e78672 PMCID:PMC3808379

[3] Xu J,Jiang D,Zhao YL,Wei L.Relationship between the genotypes of hepatitis B virus and the severity of liver diseases.Zhonghua Gan Zang Bing Za Zhi2003;11:11-3

[4] Tao H,Shi KH,Zhang L,Li J.The significance of YKL-40 protein in liver fibrosis.Inflamm Res2014;63:249-54

[5] Schuppan D.Liver fibrosis: Common mechanisms and antifibrotic therapies.Clin Res Hepatol Gastroenterol2015;39 Suppl 1:S51-9

[6] Kumagai E,Yoshio S,Sugiyama M,Ishida T,Itokawa N,Hyogo H,Ohashi T,Yoneda M,Torimura T,Watanabe S,Kanto T.Serum YKL-40 as a marker of liver fibrosis in patients with non-alcoholic fatty liver disease.Sci Rep2016;6:35282 PMCID:PMC5064386

[7] Kamal SM,He Q,Bianchi L,Nooman A,Koziel MJ.Progression of fibrosis in hepatitis C with and without schistosomiasis: correlation with serum markers of fibrosis.Hepatology2006;43:771-9

[8] Zheng M,Zhao JK,Liu RH.Determination of serum levels of YKL-40 and hyaluronic acid in patients with hepatic fibrosis due to schistosomiasis japonica and appraisal of their clinical value.Acta Trop2005;96:148-52

[9] Nunes D,Offner G,Fix O,Koziel MJ,Tumilty S,Stuver S,Cotton D.Noninvasive markers of liver fibrosis are highly predictive of liver-related death in a cohort of HCV-infected individuals with and without HIV infection..Am J Gastroenterol2010;105:1346-53

[10] Saitou Y,Yamanaka Y,Kawakita T,Sugimoto K,Nakano T.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 Gastroenterol2005;11:476-81 PMCID:PMC4250794

[11] Huang H,Mao J,Zhang J,Zheng S,Pan H.CHI3L1 is a liver-enriched, noninvasive biomarker that can be used to stage and diagnose substantial hepatic fibrosis.OMICS2015;19:339-45 PMCID:PMC4486713

[12] Fontana RJ,Bonkovsky HL,Naishadham D,Lok AS,Su GL.Serum fibrosis markers are associated with liver disease progression in non-responder patients with chronic hepatitis C.Gut2010;59:1401-9 PMCID:PMC3740000

[13] Wang L,Zhou J,Jia J.Changes in serum chitinase 3-like 1 levels correlate with changes in liver fibrosis measured by two established quantitative methods in chronic hepatitis B patients following antiviral therapy.Hepatol Res2018;48:E283-29

[14] Pungpapong S,Krishna M,Chambers K,Dickson RC,Steers J,Keaveny AP.Serum fibrosis markers can predict rapid fibrosis progression after liver transplantation for hepatitis C.Liver Transpl2008;14:1294-302

[15] Johansen JS,Moller S,Henriksen JH,Bendtsen F.Serum YKL-40 is increased in patients with hepatic fibrosis.J Hepatol2000;32:911-20

[16] He CH,Dela Cruz CS,Zhou Y,Ma B,Rosenberg SA,Nour AM,Schmidt I,Cantley L.Chitinase 3-like 1 regulates cellular and tissue responses via IL-13 receptor alpha2.Cell Rep2013;4:830-41 PMCID:PMC3988532