血清YKL-40对肝纤维化分期诊断价值的Meta分析
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摘要
目的探讨血清YKL-40蛋白对肝纤维化分期的诊断价值,为慢性肝病肝纤维化的无创诊断提供参考。方法系统检索数据库包括Pub Med、EMBASE、the Cochrane Library、Web of Science、CNKI等针对YKL-40诊断肝纤维化或者肝硬化临床价值的研究,使用质量评估方法(QUADAS-2)评价文献,采用Stata12.0软件对纳入研究进行综合定量评价,检验识别偏倚情况,分析异质性来源并且绘制森林图和汇总受试者工作曲线(SROC)。结果最终纳入9篇文献,共1592例患者,其中6篇文献对显著性肝纤维化(≥F2)进行研究;7篇对进展性肝纤维化(≥F3)进行研究。YKL-40诊断显著性肝纤维化(≥F2)的合并敏感度和特异度分别是0.78[95%可信区间(95%CI):0.69~0.85]、0.53(95%CI:0.33~0.72),阳性似然比为1.7(95%CI:1.0~2.7),阴性似然比为0.41(95%CI:0.21~0.76),优势比值比为4(95%CI:1~13)、SROC曲线下面积(AUC)是0.76(95%CI:0.72~0.80)。YKL-40诊断进展性肝纤维化(≥F3)的合并敏感度和特异度分别是0.83(95%CI:0.76~0.89)、0.72(95%CI:0.62~0.80),阳性似然比为3.0(95%CI:2.0~4.4),阴性似然比为0.23(95%CI:0.14~0.37),诊断比值比为13(95%CI:5~30)、AUC为0.85(95%CI:0.82~0.88)。结论鉴于血清YKL-40在显著性肝纤维化和进展性肝纤维化方面的诊断价值有限,其成为新的、有效的诊断肝纤维化分期的血清标志物有待进一步验证。
Objective To explore the diagnostic value of serum YKL-40 for liver fibrosis stage,and to provide a reference for noninvasive diagnosis of liver fibrosis in patients with chronic liver disease. Methods We searched Pub Med,EMBASE,the Cochrane Library,Web of Science,and CNKI for studies on the clinical value of YKL-40 in the diagnosis of liver fibrosis or cirrhosis. The quality of studies was evaluated using the QUADAS-2 tool to assess the risk of bias. Comprehensive quantitative evaluation of the included studies was performed using Stata 12. 0. The source of heterogeneity was analyzed,and the forest plot and summary receiver operating curve(SROC) were generated. Results A total of nine studies involving 1592 patients were included in the meta-analysis; six studies were conducted on significant fibrosis(≥F2),and seven studies were conducted on progressive fibrosis(≥F3). In the diagnosis of significant fibrosis(≥F2),YKL-40 had pooled sensitivity,specificity,positive likelihood ratio,negative likelihood ratio,odds ratio,and area under the SROC(AUC) of0. 78(95% confidence interval [CI]: 0. 69-0. 85),0. 53(95% CI: 0. 33-0. 72),1. 7(95% CI: 1. 0-2. 7),0. 41(95% CI: 0. 21-0. 76),4(95% CI: 1-13),and 0. 76(95% CI: 0. 72-0. 80),respectively. In the diagnosis of progressive fibrosis(≥F3),YKL-40 had pooled sensitivity,specificity,positive likelihood ratio,negative likelihood ratio,odds ratio,and AUC of 0. 83(95% CI: 0. 76-0. 89),0. 72(95% CI: 0. 62-0. 80),3. 0(95% CI: 2. 0-4. 4),0. 23(95% CI: 0. 14-0. 37),13(95% CI: 5-30),and 0. 85(95% CI: 0. 82-0. 88),respectively. Conclusion The diagnostic value of serum YKL-40 for significant and progressive liver fibrosis is limited,so it may not be a new,effective serum marker for the staging of liver fibrosis.
Objective To explore the diagnostic value of serum YKL-40 for liver fibrosis stage,and to provide a reference for noninvasive diagnosis of liver fibrosis in patients with chronic liver disease. Methods We searched Pub Med,EMBASE,the Cochrane Library,Web of Science,and CNKI for studies on the clinical value of YKL-40 in the diagnosis of liver fibrosis or cirrhosis. The quality of studies was evaluated using the QUADAS-2 tool to assess the risk of bias. Comprehensive quantitative evaluation of the included studies was performed using Stata 12. 0. The source of heterogeneity was analyzed,and the forest plot and summary receiver operating curve(SROC) were generated. Results A total of nine studies involving 1592 patients were included in the meta-analysis; six studies were conducted on significant fibrosis(≥F2),and seven studies were conducted on progressive fibrosis(≥F3). In the diagnosis of significant fibrosis(≥F2),YKL-40 had pooled sensitivity,specificity,positive likelihood ratio,negative likelihood ratio,odds ratio,and area under the SROC(AUC) of0. 78(95% confidence interval [CI]: 0. 69-0. 85),0. 53(95% CI: 0. 33-0. 72),1. 7(95% CI: 1. 0-2. 7),0. 41(95% CI: 0. 21-0. 76),4(95% CI: 1-13),and 0. 76(95% CI: 0. 72-0. 80),respectively. In the diagnosis of progressive fibrosis(≥F3),YKL-40 had pooled sensitivity,specificity,positive likelihood ratio,negative likelihood ratio,odds ratio,and AUC of 0. 83(95% CI: 0. 76-0. 89),0. 72(95% CI: 0. 62-0. 80),3. 0(95% CI: 2. 0-4. 4),0. 23(95% CI: 0. 14-0. 37),13(95% CI: 5-30),and 0. 85(95% CI: 0. 82-0. 88),respectively. Conclusion The diagnostic value of serum YKL-40 for significant and progressive liver fibrosis is limited,so it may not be a new,effective serum marker for the staging of liver fibrosis.
引文
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[12]HUANG H,WU T,MAO J,et al.CHI3L1 is a liver-enriched,noninvasive biomarker that can be used to stage and diagnose substantial hepatic fibrosis[J].OMICS,2015,19(6):339-345.
[13]KUMAGAI E,MANO Y,YOSHIO S,et al.Serum YKL-40 as a marker of liver fibrosis in patients with non-alcoholic fatty liver disease[J].Sci Rep,2016,6(1):35282.
[14]YU RM.Diagnostic value of YKL-40 and correlation with liver function and liver fibrosis indexes in patients with liver cirrhosis[J].Med J Natl Defend Forces Northwest China,2017,38(9):579-582.(in Chinese)于瑞淼.探讨YKL-40在肝硬变中的诊断价值及其与肝硬变患者肝功能和现有肝纤维化指标的相关性[J].西北国防医学杂志,2017,38(9):579-582.
[15]LI Y,LU LG.Molecular basis of hepatic fibrosis and current status of its diagnosis and treatment[J].J Clin Hepatol,2018,34(1):12-15.(in Chinese)李妍,陆伦根.肝纤维化的分子基础与临床诊治现状[J].临床肝胆病杂志,2018,34(1):12-15.
[16]BATALLER R,BRENNER DA.Liver fibrosis[J].J Clin Invest,2005,115(2):209-218.
[17]GRESSNER AM,GAO CF,GRESSNER OA.Non-invasive biomarkers for monitoring the fibrogenic process in liver:A short survey[J].World J Gastroenterol,2009,15(20):2433-2440.
[18]KJAERGAARD AD,BOJESEN SE,NORDESTGAARD BG,et al.YKL-40 and alcoholic liver and pancreas damage and disease in86,258 individuals from the general population:Cohort and mendelian randomization studies[J].Clin Chem,2014,60(11):1429-1440.
[19]NOJGAARD C,JOHANSEN JS,CHRISTENSEN E,et al.Serum levels of YKL-40 and PIIINP as prognostic markers in patients with alcoholic liver disease[J].J Hepatol,2003,39(2):179-186.
[20]GOMEZ JL,YAN X,HOLM CT,et al.Characterisation of asthma subgroups associated with circulating YKL-40 levels[J].Eur Respir J,2017,50(4).pii:1700800.
[21]SALOMON J,MATUSIAK L,NOWICKA-SUSZKO D,et al.Chitinase-3-like protein 1(YKL-40)is a new biomarker of inflammation in psoriasis[J].Mediators Inflamm,2017,2017:9538451.
[22]PAN JJ,GE YS,XU GL,et al.The expression of chitinase 3-like 1:A novel prognostic predictor for hepatocellular carcinoma[J].J Cancer Res Clin Oncol,2013,139(6):1043-1054.
[2]KUMAGAI E,MANO Y,YOSHIO S,et al.Serum YKL-40 as a marker of liver fibrosis in patients with non-alcoholic fatty liver disease[J].Sci Rep,2016,6:35282.
[3]KAMAL SM,TURNER B,HE Q,et al.Progression of fibrosis in hepatitis C with and without schistosomiasis:Correlation with serum markers of fibrosis[J].Hepatology,2006,43(4):771-779.
[4]YAN L,DENG Y,ZHOU J,et al.Serum YKL-40 as a biomarker for liver fibrosis in chronic hepatitis B patients with normal and mildly elevated ALT[J].Infection,2018,46(3):385-393.
[5]KJAERGAARD AD,JOHANSEN JS,BOJESEN SE,et al.Role of inflammatory marker YKL-40 in the diagnosis,prognosis and cause of cardiovascular and liver diseases[J].Crit Rev Clin Lab Sci,2016,53(6):396-408.
[6]SAITOU Y,SHIRAKI K,YAMANAKA Y,et al.Noninvasive estimation of liver fibrosis and response to interferon therapy by a serum fibrogenesis marker,YKL-40,in patients with HCV-associated liver disease[J].World J Gastroenterol,2005,11(4):476-481.
[7]ESMAT G,METWALLY M,ZALATA KR,et al.Evaluation of serum biomarkers of fibrosis and injury in Egyptian patients with chronic hepatitis C[J].J Hepatol,2007,46(4):620-627.
[8]SCHIAVON LL,NARCISO-SCHIAVON JL,CARVALHO FILHORJ,et al.Serum levels of YKL-40 and hyaluronic acid as noninvasive markers of liver fibrosis in haemodialysis patients with chronic hepatitis C virus infection[J].J Viral Hepat,2008,15(9):666-674.
[9]MEHTA P,PLOUTZ-SNYDER R,NANDI J,et al.Diagnostic accuracy of serum hyaluronic acid,FIBROSpect II,and YKL-40for discriminating fibrosis stages in chronic hepatitis C[J].Am JGastroenterol,2008,103(4):928-936.
[10]SCHIAVON LL,CARVALHO-FILHO RJ,NARCISO-SCHIA-VON JL,et al.YKL-40 and hyaluronic acid(HA)as noninvasive markers of liver fibrosis in kidney transplant patients with HCVchronic infection[J].Scand J Gastroenterol,2010,45(5):615-622.
[11]XIAO X,HASSANEIN T,QUN-FANG L,et al.YKL-40 expression in human hepatocellular carcinoma:A potential biomarker?[J].Hepatobiliary Pancreat Dis Int,2011,10(6):605-610.
[12]HUANG H,WU T,MAO J,et al.CHI3L1 is a liver-enriched,noninvasive biomarker that can be used to stage and diagnose substantial hepatic fibrosis[J].OMICS,2015,19(6):339-345.
[13]KUMAGAI E,MANO Y,YOSHIO S,et al.Serum YKL-40 as a marker of liver fibrosis in patients with non-alcoholic fatty liver disease[J].Sci Rep,2016,6(1):35282.
[14]YU RM.Diagnostic value of YKL-40 and correlation with liver function and liver fibrosis indexes in patients with liver cirrhosis[J].Med J Natl Defend Forces Northwest China,2017,38(9):579-582.(in Chinese)于瑞淼.探讨YKL-40在肝硬变中的诊断价值及其与肝硬变患者肝功能和现有肝纤维化指标的相关性[J].西北国防医学杂志,2017,38(9):579-582.
[15]LI Y,LU LG.Molecular basis of hepatic fibrosis and current status of its diagnosis and treatment[J].J Clin Hepatol,2018,34(1):12-15.(in Chinese)李妍,陆伦根.肝纤维化的分子基础与临床诊治现状[J].临床肝胆病杂志,2018,34(1):12-15.
[16]BATALLER R,BRENNER DA.Liver fibrosis[J].J Clin Invest,2005,115(2):209-218.
[17]GRESSNER AM,GAO CF,GRESSNER OA.Non-invasive biomarkers for monitoring the fibrogenic process in liver:A short survey[J].World J Gastroenterol,2009,15(20):2433-2440.
[18]KJAERGAARD AD,BOJESEN SE,NORDESTGAARD BG,et al.YKL-40 and alcoholic liver and pancreas damage and disease in86,258 individuals from the general population:Cohort and mendelian randomization studies[J].Clin Chem,2014,60(11):1429-1440.
[19]NOJGAARD C,JOHANSEN JS,CHRISTENSEN E,et al.Serum levels of YKL-40 and PIIINP as prognostic markers in patients with alcoholic liver disease[J].J Hepatol,2003,39(2):179-186.
[20]GOMEZ JL,YAN X,HOLM CT,et al.Characterisation of asthma subgroups associated with circulating YKL-40 levels[J].Eur Respir J,2017,50(4).pii:1700800.
[21]SALOMON J,MATUSIAK L,NOWICKA-SUSZKO D,et al.Chitinase-3-like protein 1(YKL-40)is a new biomarker of inflammation in psoriasis[J].Mediators Inflamm,2017,2017:9538451.
[22]PAN JJ,GE YS,XU GL,et al.The expression of chitinase 3-like 1:A novel prognostic predictor for hepatocellular carcinoma[J].J Cancer Res Clin Oncol,2013,139(6):1043-1054.