血清细胞角蛋白18的M30和M65水平对非酒精性脂肪性肝炎诊断价值的meta分析
车阳 王阳 王晋明 石英▲
首都医科大学附属北京佑安医院北京市肝病研究所,北京 100069
Diagnostic value of serum cytokeratin 18 levels of M30 and M65 in non-alcoholic steatohepatitis: a meta-analysis#br#
CHE Yang WANG Yang WANG Jinming SHI Ying▲
Beijing Institute of Liver Disease, Beijing YouAn Hospital, Capital Medical University, Beijing 100069, China
摘要 目的 探讨细胞角蛋白18的切割片段M30和M65对非酒精性脂肪性肝炎(NASH)的诊断价值。 方法 计算机系统性检索PubMed、EMbase、Cochrane网上图书馆和中国知网及万方数据库的文献,检索时间为自建库至2020年10月,对收集的文献进行整理及质量评价后,采用Meta-Disc1.4软件和Stata 16.0软件统计分析。 结果 本文最终纳入17篇文献,M30相关文献15篇,M65相关文献7篇,总样本量1301例。M30诊断NASH总敏感度和特异性分别为0.646(95%CI:0.606~0.684)和0.772(95%CI:0.736~0.806)。M65诊断NASH总敏感度和特异性分别为0.698(95%CI:0.639~0.752)和0.756(95%CI:0.699~0.807)。M30的集成受试者操作特征曲线法(sROC)的曲线下面积为0.8264;M65的sROC曲线下面积为0.7899。 结论 细胞角蛋白18的切割片段M30和M65对临床诊断NASH有一定意义,但是单独诊断或排除NASH效果中等,需要结合其他检查联合诊断。
关键词 :
非酒精性脂肪性肝炎 ,
血清细胞角蛋白18 ,
诊断价值 ,
meta分析
Abstract :Objective To evaluate the diagnostic value of cytokeratin 18 fragments M30 and M65 in non-alcoholic steatohepatitis (NASH). Methods Literatures from PubMed, EMbase, Cochrane online Library, CNKI and Wanfang database were systematically searched by computer. The retrieval time was from inception to October 2020. After sorting out the collected literature and evaluating its quality, Meta-Disc1.4 software and Stata 16.0 software were used for statistical analysis. Results This paper included 17 literatures, 15 literatures related to M30 and seven literatures related to M65, with a total sample size of 1301. The total sensitivity and specificity of M30 for NASH were 0.646 (95%CI:0.606-0.684) and 0.772 (95%CI: 0.736-0.806), respectively. The total sensitivity and specificity of M65 for NASH were 0.698 (95%CI: 0.639-0.752) and 0.756 (95%CI: 0.699-0.807), respectively. The area under curve of the summary receiver operator characteristic method (sROC) of M30 was 0.8264. The area under the sROC curve of M65 was 0.7899. Conclusion Cytokeratin 18 fragments M30 and M65 have certain significance for clinical diagnosis of NASH, but the effect of diagnosis alone or exclusion of NASH is moderate, and the diagnosis should be combined with other tests.
Key words :
Non-alcoholic steatohepatitis
Serum cytokeratin 18
Diagnostic value
Meta-analysis
基金资助: 首都临床诊疗技术研究及示范应用项目(Z1911 00006619064)。
通讯作者:
▲通讯作者
作者简介 : 车阳(1996.11-),女,首都医科大学附属北京佑安医院2019级生物化学与分子生物学专业在读硕士研究生,主要从事非酒精性脂肪性肝病相关研究。
[1] Vernon G,Baranova A,Younossi ZM. Systematic review:the epidemiology and natural history of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis in adults [J]. Aliment Pharmacol Ther,2011,34(3):274-285.
[2] Brunt EM,Wong VW,Nobili V,et al. Nonalcoholic fatty liver disease [J]. Nat Rev Dis Primers,2015,1:15080.
[3] Farrell GC,Larter CZ. Nonalcoholic fatty liver disease:from steatosis to cirrhosis [J]. Hepatology,2006, 43:S99-S112.
[4] 尹岩.细胞角蛋白18与临床相关疾病的研究[J].武警后勤学院学报:医学版,2016,25(8):690-693.
[5] Yilmaz Y,Dolar E,Ulukaya E,et al. Soluble forms of extracellular cytokeratin 18 may differentiate simple steatosis from nonalcoholic steatohepatitis [J]. World J Gastroenterol,2007,13(6):837-844.
[6] Chen J,Zhu Y,Zheng Q,et al. Serum cytokeratin-18 in the diagnosis of non-alcoholic steatohepatitis:A meta-analysis [J]. Hepatol Res,2014,44(8):854-862.
[7] 范建高.中国非酒精性脂肪性肝病诊疗指南(2010年修订版)[J].中国医学前沿杂志:电子版,2012,4(7):4-10.
[8] Whiting PF,Rutjes AW,Westwood ME,et al. QUADAS-2:a revised tool for the quality assessment of diagnostic accuracy studies [J]. Ann Intern Med,2011,155(8):529-536.
[9] Wieckowska A,McCullough AJ,Feldstein AE. Noninvasive diagnosis and monitoring of nonalcoholic steatohepatitis:present and future [J]. Hepatology,2007,46(2):582-589.
[10] Younossi ZM,Jarrar M,Nugent C,et al. A novel diagnostic biomarker panel for obesity-related nonalcoholic steatohepatitis(NASH)[J]. Obes Surg,2008,18(11):1430-1437.
[11] Diab DL,Yerian L,Schauer P,et al. Cytokeratin 18 fragment levels as a noninvasive biomarker for nonalcoholic steatohepatitis in bariatric surgery patients [J]. Clin Gastroenterol Hepatol,2008,6(11):1249-1254.
[12] Feldstein AE,Wieckowska A,Lopez AR,et al. Cytoke-ratin-18 fragment levels as noninvasive biomarkers for nonalcoholic steatohepatitis:a multicenter validation study [J]. Hepatology,2009,50(4):1072-1078.
[13] Malik R,Chang M,Bhaskar K,et al. The clinical utility of biomarkers and the nonalcoholic steatohepatitis CRN liver biopsy scoring system in patients with nonalcoholic fatty liver disease [J]. J Gastroenterol Hepatol,2009,24(4):564-568.
[14] Papatheodoridis GV,Hadziyannis E,Tsochatzis E,et al. Serum apoptotic caspase activity in chronic hepatitis C and nonalcoholic Fatty liver disease [J]. J Clin Gastroenterol,2010,44(4):e87-e95.
[15] Musso G,Gambino R,Durazzo M,et al. Noninvasive assessment of liver disease severity with liver fat score and CK-18 in NAFLD:Prognostic value of liver fat equation goes beyond hepatic fat estimation [J]. Hepatology,2010, 51(2):715-717.
[16] Joka D,Wahl K,Moeller S,et al. Prospective biopsy-controlled evaluation of cell death biomarkers for prediction of liver fibrosis and nonalcoholic steatohepatitis [J]. Hepatology,2012,55(2):455-464.
[17] Younossi ZM,Page S,Rafiq N,et al. A biomarker panel for non-alcoholic steatohepatitis (NASH) and NASH-related fibrosis [J]. Obes Surg,2011,21(4):431-439.
[18] Pirvulescu I,Gheorghe L,Csiki I,et al. Noninvasive clinical model for the diagnosis of nonalcoholic steatohepatitis in overweight and morbidly obese patients undergoing bariatric surgery [J]. Chirurgia(Bucur),2012,107(6):772-779.
[19] Grigorescu M,Crisan D,Radu C,et al. A novel pathoph-ysiological-based panel of biomarkers for the diagnosis of nonalcoholic steatohepatitis [J]. J Physiol Pharmacol,2012,63(4):347-353.
[20] Pimentel CF,Jiang ZG,Otsubo T,et al. Poor Inter-test Reliability Between CK18 Kits as a Biomarker of NASH [J]. Dig Dis Sci,2016,61(3):905-912.
[21] 沈峰.细胞角蛋白-18联合受控衰减参数二步法无创鉴别非酒精性脂肪性肝炎的临床研究[J].中华肝脏病杂志,2016,24(6):429-434.
[22] Valva P,Rios D,Casciato P,et al. Nonalcoholic fatty liver disease:biomarkers as diagnostic tools for liver damage assessment in adult patients from Argentina [J]. Eur J Gastroenterol Hepatol,2018,30(6):637-644.
[23] Zheng KI,Liu WY,Pan XY,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 [J]. BMJ Open Diabetes Res Care,2020,8(1):e001174.
[24] Chuah KH,Wan Yusoff WNI,Sthaneshwar P,et al. MACK-3(combination of hoMa,Ast and CK18): A promising novel biomarker for fibrotic non-alcoholic steatohepatitis [J]. Liver Int,2019,39(7):1315-1324.
[25] Feldstein AE,Lopez R,Tamimi TA,et al. Mass spectrometric profiling of oxidized lipid products in human nonalcoholic fatty liver disease and nonalcoholic steat-ohepatitis [J]. J Lipid Res,2010,51(10):3046-3054.
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