北京大学人民医院刘文玲

1、北京大学人民医院北京大学人民医院 刘文玲刘文玲心肌病与丙型肝炎病毒感染心肌病与丙型肝炎病毒感染relationship between cardiomyopathies and hepatitis c virus infectioncopyright restrictions may apply.elliott, p. et al. eur heart j 2008 29:270-276; doi:10.1093/eurheartj/ehm342summary of proposed classification systemcopyright 2006 american heart asso

2、ciationmaron, b. j. et al. circulation 2006;113:1807-1816maron, b. j. et al. circulation 2006;113:1807-1816primary cardiomyopathies in which the clinically relevant disease processes solely or primary cardiomyopathies in which the clinically relevant disease processes solely or predominantly involve

3、 the myocardiumpredominantly involve the myocardium 近十年来，丙型肝炎病毒（近十年来，丙型肝炎病毒（hcvhcv）感染）感染与心肌炎、心肌病、动脉粥样硬化等心血管与心肌炎、心肌病、动脉粥样硬化等心血管疾病相关研究陆续开展，对疾病相关研究陆续开展，对hcvhcv是否是是否是cvdcvd的的相关危险因素进行了深入研究。相关危险因素进行了深入研究。 然而，不同国家（地区）、不同人群的然而，不同国家（地区）、不同人群的研究结果研究结果不尽一致不尽一致。 1995 japan matsumori dcm 1995 japan matsumori dcm

4、1997 japan okabe myocarditis1997 japan okabe myocarditis1999 japan takeda1999 japan takeda myocarditismyocarditis2002 japan frustaci 2002 japan frustaci myocarditismyocarditis 1996 japan matsumori hcm 1996 japan matsumori hcmtime country author diseasetime country author disease阳性结论阳性结论1998 greece d

5、alekos dcm1998 greece dalekos dcm1998 germany grumbach myocarditis ,dcm1998 germany grumbach myocarditis ,dcmtime country author diseasetime country author disease阴性结论阴性结论1999 italy prati dcm1999 italy prati dcm 20 pg/ml 20 pg/mlincreased bnp (%)31*25*55.4% *cardiac troponin t 10 pg/ml, troponin i 1

6、00 pg/mlplasma bnp in patients with hcv hepatitisdetection of negative strands of hcv rna in the heart of a patients with dcm by in situ hybridization 200hcv hepatitisdcmimmunohistochemical staining against hcv proteinimmunohistochemical staining of hcv core protein in the heart from patients with a

7、rvc/dchronic inflammationdcmarvc/dhcmhypertrophyhcv infectionmyocyte lossfibrosisacute hepatitischronic hepatitisliver cirrhosismyocardialfibrosisdcmacute myocarditischronicinflammationhepaticfailurehcchcm85%20%6%4%hcv hepatitishcv cardiomyopathiesviral infection of the heartdiffusechf/dcmsystolic h

8、fregionalaneurysmsubendocardialrcmdiastolic hfarvc/dlv aneurysmrandomhypertrophy/hcmvirusreceptormyocytefibroblastcompleterecoverydiffusehypokinesisregionalabnormalitysubendocardiallesionsincreasedwall thicknessunclassifiedabnormalityviral myocarditischf/dcmsystolic hfhcmrcmarvc/ddiastolic hfhepatit

9、is c virus lv aneurysmarvchcmdcmmyocarditismatsumori a circ res 2005;96:144-147我国我国hcv患者心脏损害的研究患者心脏损害的研究 我国一般人群抗我国一般人群抗-hcv-hcv阳性率为阳性率为3.2%3.2%，丙型肝炎抗体阳性患者约丙型肝炎抗体阳性患者约40004000万；万； 与心血管疾病一样，与心血管疾病一样，hcvhcv感染也是严感染也是严重危害人民健康的卫生问题。重危害人民健康的卫生问题。研研 究究 对对 象象n病例组：连续选取病例组：连续选取2006年年3月月2007年年7月于月于北京佑安医院及解放军北京佑

10、安医院及解放军302医院两家三级甲等医院两家三级甲等传染病专科医院诊治的传染病专科医院诊治的hcv感染患者感染患者n对照组：随机选取与入选病例年龄、性别、体对照组：随机选取与入选病例年龄、性别、体重匹配的正常健康人作为对照。重匹配的正常健康人作为对照。 研 究 对 象hcv感染者入选标准感染者入选标准 血清抗血清抗hcv抗体阳性；抗体阳性； 血清血清hcv rna 阳性；阳性； hcv感染者排除标准感染者排除标准 其他肝病、包括艾滋病毒、立克次体或螺旋 体在内的其他感染性疾病、妊娠、产后妇女、 现有或既往酗酒或吸毒、肿瘤、心血管系统 外其他各系统慢性疾病、不同意参与者。对照选择对照选择 研 究

11、 对 象 与入选病例年龄、性别匹配的与入选病例年龄、性别匹配的 正常健康人作为对照。正常健康人作为对照。研 究 路 线 研究对象收集研究对象收集 设计调查表格设计调查表格 收集临床资料收集临床资料 超声心动图、心电图检查超声心动图、心电图检查 留取非抗凝血留取非抗凝血10ml 2006.1 2007.8血清生化标志物检测血清生化标志物检测 ctnictni nt-probnp nt-probnp hs-crp hs-crp mmp-9 mmp-9 flc flc 2007.3 2007.9 数据总结分析数据总结分析 临床评估临床评估 血清生化标志物评估血清生化标志物评估 超声心动图评估超声心动

12、图评估 2007.10 本文将本文将“心电图异常和心电图异常和/ /或具有心血或具有心血管病史管病史”定义为定义为“心血管异常心血管异常”，有心，有心血管异常患者共血管异常患者共2727例。例。 心脏血清生化标志物评估心脏血清生化标志物评估病例组与健康对照组间比较 * p p0.050.05，中位数，中位数，n=131n=131 无心血管异常病例与相应健康对照间比较 * p p0.050.05，中位数，中位数,n=104,n=104 *心血管异常患者与相应健康对照间比较 * p p0.050.05，中位数，中位数,n=27,n=27 *病例组与对照组血清病例组与对照组血清nt-probnp水平

13、比较（中位数，水平比较（中位数，*p0.05） 超声心动图没有显示出心脏结构的超声心动图没有显示出心脏结构的异常，但心血管异常风险较高患者的左异常，但心血管异常风险较高患者的左室收缩功能降低室收缩功能降低。nhcvhcv感染导致血清感染导致血清nt-probnpnt-probnp、flcflc、flcflc水平及水平及flc/ flc/ 升高。升高。n上述指标是心肌损伤的标志上述指标是心肌损伤的标志结论结论我国心肌病患者我国心肌病患者hcv感染率研究感染率研究心肌病患者心肌病患者hcv感染回顾性研究感染回顾性研究研究对象研究对象北京大学人民医院北京大学人民医院2003年年-2008年心内年心内

14、科住院的科住院的dcm,hcm患者患者dcm hcm 诊断标准诊断标准nhcm ： who 1995ndcm criteria： nef 20 pg/ml 20 pg/mlincreased bnp (%)31*25*55.4% *cardiac troponin t 10 pg/ml, troponin i 100 pg/mlplasma bnp in patients with hcv hepatitisdetection of negative strands of hcv rna in the heart of a patients with dcm by in situ hybrid

15、ization 200hcv hepatitisdcmimmunohistochemical staining against hcv proteinimmunohistochemical staining of hcv core protein in the heart from patients with arvc/dchronic inflammationdcmarvc/dhcmhypertrophyhcv infectionmyocyte lossfibrosisacute hepatitischronic hepatitisliver cirrhosismyocardialfibro

16、sisdcmacute myocarditischronicinflammationhepaticfailurehcchcm85%20%6%4%hcv hepatitishcv cardiomyopathiesviral infection of the heartdiffusechf/dcmsystolic hfregionalaneurysmsubendocardialrcmdiastolic hfarvc/dlv aneurysmrandomhypertrophy/hcmvirusreceptormyocytefibroblastcompleterecoverydiffusehypoki

17、nesisregionalabnormalitysubendocardiallesionsincreasedwall thicknessunclassifiedabnormalityviral myocarditischf/dcmsystolic hfhcmrcmarvc/ddiastolic hfhepatitis c virus lv aneurysmarvchcmdcmmyocarditismatsumori a circ res 2005;96:144-147 impairment of myocardium in patients with hepatitis c virus inf

18、ection in china nin china, the prevalence of hcv infection is about 3.2 % in the general populationnestimated 40106 individuals infected hcvprevalence of hcv infection in chinapopulationn87 hcv-infected patients n87 control healthy individuals serum hcv antibody (+)； serum hcv rna (+)； diagnosis of

19、hcv infectionmarkers cases collection history ucg ecg blood sample 10ml 2006.1 2007.8serum biomarkers test ctnictni nt-probnp nt-probnp hs-crp hs-crp mmp-9 mmp-9 flc flc 2007.3 2007.9 data analysis clinical evaluation serum biomarkers evaluation 2007.10 clinical featuresbiomarkers total patients wit

20、h hcv vs normal controls * p p0.050.05，medianmedian，n=131n=131 patientcontrolpatients with hcv but without cardiac manifestation vs normal controls* p p0.050.05，median,n=104median,n=104 *patientcontrolpatients with hcv and cardiac manifestation vs normal controls* p p0.050.05，median,n=27median,n=27

21、*patientcontrolnt-probnp in patients with hcv vs normal controls （median，*p0.05） patientcontrol total with cardiac abnormal without cardiac abnormalno difference ucg in patients with hcv and normal controls nhcv infection cause nt-probnp, flc,flcand flc/ increase in chinesenthese markers indicate the impairment of myocardiumconclusion hcv infection in patients with cardiomyopathies in china study -retrospectivelypatients with cardiomyopathies hospitalized in peking univ. peoples hosp.fro