抗核抗体对自身免疫性肝炎诊断价值的Meta分析
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摘要
目的评价抗核抗体(ANA)对自身免疫性肝炎(AIH)的诊断价值。方法计算机检索中国期刊全文数据库(CNKI)、万方数据期刊全文数据库、中国生物医学文献检索数据库(CBM)、维普中文科技期刊全文数据库(VIP)、PubMed、EMbase、Medline、The Cochrane Library,检索时限均从建库至2018年10月。由2位作者根据纳入和排除标准独立筛选文献,提取资料并对所纳入研究进行质量评价。应用修改后的质量评价工具(QUADAS-2)评价文献质量。采用Meta-Disc 1.4软件进行Meta分析,计算合并敏感度、合并特异度、合并诊断优势比,绘制汇总受试者工作特征曲线(SROC)并计算曲线下面积(AUC),采用敏感性分析评估结果的稳定性。采用Deek's漏斗图非对称检验评估是否存在发表偏倚。结果共纳入27项研究,包含1 220例AIH患者,4 580例对照者。异质性检验提示存在非阈值效应引起的明显异质性,采用随机效应模型对27项研究进行Meta分析,合并敏感度、合并特异度、合并诊断优势比、SROC曲线下面积(AUC)分别为0.76(95%CI 0.73～0.78)、0.86(95%CI 0.85～0.87)、24.44(95%CI 15.81～37.78)、0.907 4。Deek's漏斗图非对称检验提示不存在明显发表偏倚。结论 ANA检测对AIH临床诊断价值较高,具有较高的敏感度和特异度。
Objective To evaluate the diagnostic value of antinuclear antibody(ANA) in autoimmune hepatitis(AIH).Methods The CNKI, Wanfang, CBM, VIP, PubMed, EMbase, Medline and The Cochrane Library were retrieved by computer. The retrieval time was from the establishment of the database to October 2018. Literature was independently screened by two authors according to inclusion and exclusion criteria. Data were extracted and quality evaluation of the included studies was conducted. The revised quality assessment tool(QUADAS 2) was used to evaluate the quality of literature. Meta-Disc 1.4 software was used for meta-analysis to calculate merge sensitivity, merge specificity, merge diagnostic advantage ratio, draw SROC and calculate the area under the curve(AUC). The stability of the results was evaluated by sensitivity analysis. Deek's funnel graph asymmetry test was used to evaluate publication bias. Results A total of 27 studies including 1 220 AIH patients and 4 580 controls were included. Heterogeneity test indicated that there was significant heterogeneity caused by non-threshold effect. 27 studies were meta-analyzed by random effect model. The combined sensitivity, combined specificity, combined diagnostic advantage ratio and area under ROC curve(AUC) were 0.76(95% CI 0.73～0.78), 0.86(95% CI 0.85～0.87), 24.44(95% CI 15.81～37.78) and 0.907 4, respectively. Deek's funnel graph asymmetry test showed that there was no obvious publication bias.Conclusion The detection of ANA is of high value in clinical diagnosis of AIH with high sensitivity and specificity.
Objective To evaluate the diagnostic value of antinuclear antibody(ANA) in autoimmune hepatitis(AIH).Methods The CNKI, Wanfang, CBM, VIP, PubMed, EMbase, Medline and The Cochrane Library were retrieved by computer. The retrieval time was from the establishment of the database to October 2018. Literature was independently screened by two authors according to inclusion and exclusion criteria. Data were extracted and quality evaluation of the included studies was conducted. The revised quality assessment tool(QUADAS 2) was used to evaluate the quality of literature. Meta-Disc 1.4 software was used for meta-analysis to calculate merge sensitivity, merge specificity, merge diagnostic advantage ratio, draw SROC and calculate the area under the curve(AUC). The stability of the results was evaluated by sensitivity analysis. Deek's funnel graph asymmetry test was used to evaluate publication bias. Results A total of 27 studies including 1 220 AIH patients and 4 580 controls were included. Heterogeneity test indicated that there was significant heterogeneity caused by non-threshold effect. 27 studies were meta-analyzed by random effect model. The combined sensitivity, combined specificity, combined diagnostic advantage ratio and area under ROC curve(AUC) were 0.76(95% CI 0.73～0.78), 0.86(95% CI 0.85～0.87), 24.44(95% CI 15.81～37.78) and 0.907 4, respectively. Deek's funnel graph asymmetry test showed that there was no obvious publication bias.Conclusion The detection of ANA is of high value in clinical diagnosis of AIH with high sensitivity and specificity.
引文
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[3] Kinoshita H,Omagari K,Whittingham S,et al.Autoimmune cholangitis and primary biliary cirrhosis—an autoimmune enigma[J].Liver,1999,19(2):122-128.DOI:10.1111/j.1478-3231.1999.tb00021.x.
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[6] 黄加权,郑志想,黄铁军,等.慢性肝病自身抗体的检测及其与自身免疫性肝病的相关性[J].华中科技大学学报医学版,2006,35(2):195-198.DOI:10.3870/j.issn.1672-0741.2006.02.015.
[7] 刘宁,谭立明,董叶,等.原发性胆汁性肝硬化患者自身抗体测定的意义[J].世界华人消化杂志,2007,15(21):2358-2361.DOI:10.3969/j.issn.1009-3079.2007.21.021.
[8] 张嘉琳,罗燕飞,陈达强,等.联合检测自身抗体对自身免疫性肝炎的诊断意义[J].广东医学,2007,28(12):1962-1963.DOI:10.3969/j.issn.1001-9448.2007.12.030.
[9] 刘妍,闫惠平,檀玉芬,等.原发性胆汁性肝硬化患者抗SP100抗体与核点型抗核抗体的检测[J].临床检验杂志,2009,27(4):256-258.DOI:10.13602/j.cnki.jcls.2009.04.025.
[10] 姜慧英,刘妍.原发性胆汁性肝硬化患者抗gp210抗体与核膜型抗核抗体的检测及其临床意义[J].中国实验诊断学,2010,14(11):1796-1798.DOI:10.3969/j.issn.1007-4287.2010.11.042.
[11] 邓纪望,蔡燕玲,何以雅.不同荧光模式ANA、ASMA在自身免疫性肝炎与慢性丙型肝炎中的诊断价值[J].实验与检验医学,2010,28(2):147-148.DOI:10.3969/j.issn.1674-1129.2010.02.016.
[12] 王蓉,覃沙,洪华,等.抗核抗体及抗肝抗原抗体检测在诊断自身免疫性肝病中的应用[J].国际检验医学杂志,2010,31(11):1226-1228.DOI:10.3969/j.issn.1673-4130.2010.11.010.
[13] 马琼麟,曾维,黄静,等.自身抗体检测在自身免疫性肝炎诊断的临床评价[J].中国现代医生,2010,48(2):87-88.DOI:10.3969/j.issn.1673-9701.2010.02.048.
[14] 陈丽,龚丽敏,曹海芬.肝抗原自身抗体检测在自身免疫性肝病诊断中的意义[J].中国卫生检验杂志,2010,20(1):139-140,224.
[15] Bostrom EA,Ekstedt M,Kechagias S,et al.Resistin is associated with breach of tolerance and anti-nuclear antibodies in patients with hepatobiliary inflammation[J].Scand J Immunol,2011,74(5):463-470.DOI:10.1111/j.1365-3083.2011.02592.x.
[16] 陈瀑,严立,叶荻庆,等.不明原因肝功能异常患者自身抗体的检测及对自身免疫性肝病的临床意义[J].重庆医学,2011,40(3):239-241.DOI:10.3969/j.issn.1671-8348.2011.03.012.
[17] 牟君成,赵昕,王文昕.肝抗原自身抗体检测对自身免疫性肝病的诊断价值探讨[J].国际检验医学杂志,2011,32(4):451-452,454.DOI:10.3969/j.issn.1673-4130.2011.04.009.
[18] 谭立明,王园园,李华,等.161例自身免疫性肝病患者相关自身抗体检测的临床研究[J].免疫学杂志,2012,28(12):1061-1064.DOI:10.13431/j.cnki.immunol.j.20120246.
[19] Efe C,Ozaslan E,Wahlin S,et al.Antibodies to soluble liver antigen in patients with various liver diseases:a multicentre study[J].Liver Int,2013,33(2):190-196.DOI:10.1111/liv.12022.
[20] 刘燕京.自身抗体在自身免疫性肝病中的表达及临床价值[J].中国实用医药,2013,8(28):102-103.DOI:10.3969/j.issn.1673-7555.2013.28.078.
[21] 任妹,廖永强,彭可君,等.多种自身抗体联合检测对自身免疫性肝病的诊断价值[J].临床与病理杂志,2014,34(4):385-389.DOI:10.11714/j.issn.2095-6959.2014.04.013.
[22] 张宏宇,朱珍,徐昕,等.自身免疫性肝病患者血清中自身抗体的动态变化及相关性分析[J].重庆医学,2014,43(16):2032-2034.DOI:10.3969/j.issn.1671-8348.2014.16.021.
[23] 欧阳艳君.血清自身抗体和抗核抗体检测在自身免疫性肝病诊断中的价值[J].实用临床医药杂志,2015,19(23):191-192.DOI:10.7619/jcmp.201523075.
[24] 章英宏.自身抗体检测对肝功能异常患者自身免疫性肝病的诊疗有效性评价[J].现代实用医学,2016,28(2):209-210.DOI:10.3969/j.issn.1671-0800.2016.02.036.
[25] 周泉,李艳,周心房.自身免疫性肝病与病毒性肝病患者自身抗体和肝功能的相关性研究[J].职业与健康,2016,32(1):69-72.DOI:10.13329/j.cnki.zyyjk.2016.0067.
[26] 刘婕,赵斌.肝病相关自身抗体在不同类型肝炎患者中的表达特点及价值分析[J].解放军医药杂志,2017,29(9):67-70.DOI:10.3969/j.issn.2095-140X.2017.09.017.
[27] 汪永强,周振忠,项明,等.肝病相关自身抗体与Th17、Treg细胞在自身免疫性肝炎中的临床意义[J].中国卫生检验杂志,2017,27(10):1422-1425.
[28] 曹梦杰.自身免疫性肝病患者自身免疫性肝病抗体谱检测意义[J].包头医学院学报,2017,33(11):62-63.DOI:10.16833/j.cnki.jbmc.2017.11.026.
[29] 贾继东.自身抗体检查在自身免疫性肝病诊断中的应用[J].中华检验医学杂志,2003,26(2):55-57.DOI:10.3760/j:issn:1009-9158.2003.02.026.
[30] Czaja AJ.Autoantibodies as prognostic markers in autoimmune liver disease[J].Dig Dis Sci,2010,55(8):2144-2161.DOI:10.1007/s10620-010-1268-4.
[31] Achenza MI,Meda F,Brunetta E,et al.Serum autoantibodies for the diagnosis and management of autoimmune liver diseases[J].Expert Rev Gastroenterol Hepatol,2012,6(6):717-729.DOI:10.1586/egh.12.58.
[32] Self SE.Autoantibody testing for autoimmune disease[J].Clin Chest Med,2010,31(3):415-422.DOI:10.1016/j.ccm.2010.04.001.
[33] 范列英,仲人前,王皓,等.可溶性肝抗原的克隆、表达及初步临床应用[J].上海免疫学杂志,2002,22(3):197-199,196.DOI:10.3969/j.issn.1001-2478.2002.03.015.
[34] Bowlus CL,Gershwin ME.The diagnosis of primary biliary cirrhosis[J].Autoimmun Rev,2014,13(4-5):441-444.DOI:10.1016/j.autrev.2014.01.041.
[35] 谭朝霞,唐玉兰,高燕,等.自身抗体在乙型病毒性肝炎和自身免疫性肝炎中的特点分析[J].第三军医大学学报,2016,38(15):1762-1766.DOI:10.16016/j.1000-5404.201511162.
[2] Cassani F,Cataleta M,Valentini P,et al.Serum autoantibodies in chronic hepatitis C:comparison with autoimmune hepatitis and impact on the disease profile[J].Hepatology,1997,26(3):561-566.DOI:10.1002/hep.510260305.
[3] Kinoshita H,Omagari K,Whittingham S,et al.Autoimmune cholangitis and primary biliary cirrhosis—an autoimmune enigma[J].Liver,1999,19(2):122-128.DOI:10.1111/j.1478-3231.1999.tb00021.x.
[4] Miyakawa H,Kawashima Y,Kitazawa E,et al.Low frequency of anti-SLA/LP autoantibody in Japanese adult patients with autoimmune liver diseases:analysis with recombinant antigen assay[J].J Autoimmun,2003,21(1):77-82.DOI:10.1016/S0896-8411(03)00084-2.
[5] 张炳昌,焦玉莲,王晓玲.自身免疫性肝病患者生化指标及自身抗体的研究[J].中华检验医学杂志,2004,27(3):42-43.DOI:10.3760/j:issn:1009-9158.2004.03.018.
[6] 黄加权,郑志想,黄铁军,等.慢性肝病自身抗体的检测及其与自身免疫性肝病的相关性[J].华中科技大学学报医学版,2006,35(2):195-198.DOI:10.3870/j.issn.1672-0741.2006.02.015.
[7] 刘宁,谭立明,董叶,等.原发性胆汁性肝硬化患者自身抗体测定的意义[J].世界华人消化杂志,2007,15(21):2358-2361.DOI:10.3969/j.issn.1009-3079.2007.21.021.
[8] 张嘉琳,罗燕飞,陈达强,等.联合检测自身抗体对自身免疫性肝炎的诊断意义[J].广东医学,2007,28(12):1962-1963.DOI:10.3969/j.issn.1001-9448.2007.12.030.
[9] 刘妍,闫惠平,檀玉芬,等.原发性胆汁性肝硬化患者抗SP100抗体与核点型抗核抗体的检测[J].临床检验杂志,2009,27(4):256-258.DOI:10.13602/j.cnki.jcls.2009.04.025.
[10] 姜慧英,刘妍.原发性胆汁性肝硬化患者抗gp210抗体与核膜型抗核抗体的检测及其临床意义[J].中国实验诊断学,2010,14(11):1796-1798.DOI:10.3969/j.issn.1007-4287.2010.11.042.
[11] 邓纪望,蔡燕玲,何以雅.不同荧光模式ANA、ASMA在自身免疫性肝炎与慢性丙型肝炎中的诊断价值[J].实验与检验医学,2010,28(2):147-148.DOI:10.3969/j.issn.1674-1129.2010.02.016.
[12] 王蓉,覃沙,洪华,等.抗核抗体及抗肝抗原抗体检测在诊断自身免疫性肝病中的应用[J].国际检验医学杂志,2010,31(11):1226-1228.DOI:10.3969/j.issn.1673-4130.2010.11.010.
[13] 马琼麟,曾维,黄静,等.自身抗体检测在自身免疫性肝炎诊断的临床评价[J].中国现代医生,2010,48(2):87-88.DOI:10.3969/j.issn.1673-9701.2010.02.048.
[14] 陈丽,龚丽敏,曹海芬.肝抗原自身抗体检测在自身免疫性肝病诊断中的意义[J].中国卫生检验杂志,2010,20(1):139-140,224.
[15] Bostrom EA,Ekstedt M,Kechagias S,et al.Resistin is associated with breach of tolerance and anti-nuclear antibodies in patients with hepatobiliary inflammation[J].Scand J Immunol,2011,74(5):463-470.DOI:10.1111/j.1365-3083.2011.02592.x.
[16] 陈瀑,严立,叶荻庆,等.不明原因肝功能异常患者自身抗体的检测及对自身免疫性肝病的临床意义[J].重庆医学,2011,40(3):239-241.DOI:10.3969/j.issn.1671-8348.2011.03.012.
[17] 牟君成,赵昕,王文昕.肝抗原自身抗体检测对自身免疫性肝病的诊断价值探讨[J].国际检验医学杂志,2011,32(4):451-452,454.DOI:10.3969/j.issn.1673-4130.2011.04.009.
[18] 谭立明,王园园,李华,等.161例自身免疫性肝病患者相关自身抗体检测的临床研究[J].免疫学杂志,2012,28(12):1061-1064.DOI:10.13431/j.cnki.immunol.j.20120246.
[19] Efe C,Ozaslan E,Wahlin S,et al.Antibodies to soluble liver antigen in patients with various liver diseases:a multicentre study[J].Liver Int,2013,33(2):190-196.DOI:10.1111/liv.12022.
[20] 刘燕京.自身抗体在自身免疫性肝病中的表达及临床价值[J].中国实用医药,2013,8(28):102-103.DOI:10.3969/j.issn.1673-7555.2013.28.078.
[21] 任妹,廖永强,彭可君,等.多种自身抗体联合检测对自身免疫性肝病的诊断价值[J].临床与病理杂志,2014,34(4):385-389.DOI:10.11714/j.issn.2095-6959.2014.04.013.
[22] 张宏宇,朱珍,徐昕,等.自身免疫性肝病患者血清中自身抗体的动态变化及相关性分析[J].重庆医学,2014,43(16):2032-2034.DOI:10.3969/j.issn.1671-8348.2014.16.021.
[23] 欧阳艳君.血清自身抗体和抗核抗体检测在自身免疫性肝病诊断中的价值[J].实用临床医药杂志,2015,19(23):191-192.DOI:10.7619/jcmp.201523075.
[24] 章英宏.自身抗体检测对肝功能异常患者自身免疫性肝病的诊疗有效性评价[J].现代实用医学,2016,28(2):209-210.DOI:10.3969/j.issn.1671-0800.2016.02.036.
[25] 周泉,李艳,周心房.自身免疫性肝病与病毒性肝病患者自身抗体和肝功能的相关性研究[J].职业与健康,2016,32(1):69-72.DOI:10.13329/j.cnki.zyyjk.2016.0067.
[26] 刘婕,赵斌.肝病相关自身抗体在不同类型肝炎患者中的表达特点及价值分析[J].解放军医药杂志,2017,29(9):67-70.DOI:10.3969/j.issn.2095-140X.2017.09.017.
[27] 汪永强,周振忠,项明,等.肝病相关自身抗体与Th17、Treg细胞在自身免疫性肝炎中的临床意义[J].中国卫生检验杂志,2017,27(10):1422-1425.
[28] 曹梦杰.自身免疫性肝病患者自身免疫性肝病抗体谱检测意义[J].包头医学院学报,2017,33(11):62-63.DOI:10.16833/j.cnki.jbmc.2017.11.026.
[29] 贾继东.自身抗体检查在自身免疫性肝病诊断中的应用[J].中华检验医学杂志,2003,26(2):55-57.DOI:10.3760/j:issn:1009-9158.2003.02.026.
[30] Czaja AJ.Autoantibodies as prognostic markers in autoimmune liver disease[J].Dig Dis Sci,2010,55(8):2144-2161.DOI:10.1007/s10620-010-1268-4.
[31] Achenza MI,Meda F,Brunetta E,et al.Serum autoantibodies for the diagnosis and management of autoimmune liver diseases[J].Expert Rev Gastroenterol Hepatol,2012,6(6):717-729.DOI:10.1586/egh.12.58.
[32] Self SE.Autoantibody testing for autoimmune disease[J].Clin Chest Med,2010,31(3):415-422.DOI:10.1016/j.ccm.2010.04.001.
[33] 范列英,仲人前,王皓,等.可溶性肝抗原的克隆、表达及初步临床应用[J].上海免疫学杂志,2002,22(3):197-199,196.DOI:10.3969/j.issn.1001-2478.2002.03.015.
[34] Bowlus CL,Gershwin ME.The diagnosis of primary biliary cirrhosis[J].Autoimmun Rev,2014,13(4-5):441-444.DOI:10.1016/j.autrev.2014.01.041.
[35] 谭朝霞,唐玉兰,高燕,等.自身抗体在乙型病毒性肝炎和自身免疫性肝炎中的特点分析[J].第三军医大学学报,2016,38(15):1762-1766.DOI:10.16016/j.1000-5404.201511162.