北京大學(xué)人民醫(yī)院劉文玲

1、北京大學(xué)人民醫(yī)院北京大學(xué)人民醫(yī)院 劉文玲劉文玲心肌病與丙型肝炎病毒感染心肌病與丙型肝炎病毒感染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 近十年來，丙型肝炎病毒（近十年來，丙型肝炎病毒（hcvhcv）感染）感染與心肌炎、心肌病、動脈粥樣硬化等心血管與心肌炎、心肌病、動脈粥樣硬化等心血管疾病相關(guān)研究陸續(xù)開展，對疾病相關(guān)研究陸續(xù)開展，對hcvhcv是否是是否是cvdcvd的的相關(guān)危險因素進行了深入研究。相關(guān)危險因素進行了深入研究。 然而，不同國家（地區(qū)）、不同人群的然而，不同國家（地區(qū)）、不同人群的研究結(jié)果研究結(jié)果不盡一致不盡一致。 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陽性結(jié)論陽性結(jié)論1998 greece d

5、alekos dcm1998 greece dalekos dcm1998 germany grumbach myocarditis ,dcm1998 germany grumbach myocarditis ,dcmtime country author diseasetime country author disease陰性結(jié)論陰性結(jié)論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我國我國hcv患者心臟損害的研究患者心臟損害的研究 我國一般人群抗我國一般人群抗-hcv-hcv陽性率為陽性率為3.2%3.2%，丙型肝炎抗體陽性患者約丙型肝炎抗體陽性患者約40004000萬；萬； 與心血管疾病一樣，與心血管疾病一樣，hcvhcv感染也是嚴感染也是嚴重危害人民健康的衛(wèi)生問題。重危害人民健康的衛(wèi)生問題。研研 究究 對對 象象n病例組：連續(xù)選取病例組：連續(xù)選取2006年年3月月2007年年7月于月于北京佑安醫(yī)院及解放軍北京佑

10、安醫(yī)院及解放軍302醫(yī)院兩家三級甲等醫(yī)院兩家三級甲等傳染病?？漆t(yī)院診治的傳染病?？漆t(yī)院診治的hcv感染患者感染患者n對照組：隨機選取與入選病例年齡、性別、體對照組：隨機選取與入選病例年齡、性別、體重匹配的正常健康人作為對照。重匹配的正常健康人作為對照。 研 究 對 象hcv感染者入選標準感染者入選標準 血清抗血清抗hcv抗體陽性；抗體陽性； 血清血清hcv rna 陽性；陽性； hcv感染者排除標準感染者排除標準 其他肝病、包括艾滋病毒、立克次體或螺旋 體在內(nèi)的其他感染性疾病、妊娠、產(chǎn)后婦女、 現(xiàn)有或既往酗酒或吸毒、腫瘤、心血管系統(tǒng) 外其他各系統(tǒng)慢性疾病、不同意參與者。對照選擇對照選擇 研 究

11、 對 象 與入選病例年齡、性別匹配的與入選病例年齡、性別匹配的 正常健康人作為對照。正常健康人作為對照。研 究 路 線 研究對象收集研究對象收集 設(shè)計調(diào)查表格設(shè)計調(diào)查表格 收集臨床資料收集臨床資料 超聲心動圖、心電圖檢查超聲心動圖、心電圖檢查 留取非抗凝血留取非抗凝血10ml 2006.1 2007.8血清生化標志物檢測血清生化標志物檢測 ctnictni nt-probnp nt-probnp hs-crp hs-crp mmp-9 mmp-9 flc flc 2007.3 2007.9 數(shù)據(jù)總結(jié)分析數(shù)據(jù)總結(jié)分析 臨床評估臨床評估 血清生化標志物評估血清生化標志物評估 超聲心動圖評估超聲心動

12、圖評估 2007.10 本文將本文將“心電圖異常和心電圖異常和/ /或具有心血或具有心血管病史管病史”定義為定義為“心血管異常心血管異?！?，有心，有心血管異常患者共血管異?；颊吖?727例。例。 心臟血清生化標志物評估心臟血清生化標志物評估病例組與健康對照組間比較 * p p0.050.05，中位數(shù)，中位數(shù)，n=131n=131 無心血管異常病例與相應(yīng)健康對照間比較 * p p0.050.05，中位數(shù)，中位數(shù),n=104,n=104 *心血管異常患者與相應(yīng)健康對照間比較 * p p0.050.05，中位數(shù)，中位數(shù),n=27,n=27 *病例組與對照組血清病例組與對照組血清nt-probnp水平

13、比較（中位數(shù)，水平比較（中位數(shù)，*p0.05） 超聲心動圖沒有顯示出心臟結(jié)構(gòu)的超聲心動圖沒有顯示出心臟結(jié)構(gòu)的異常，但心血管異常風(fēng)險較高患者的左異常，但心血管異常風(fēng)險較高患者的左室收縮功能降低室收縮功能降低。nhcvhcv感染導(dǎo)致血清感染導(dǎo)致血清nt-probnpnt-probnp、flcflc、flcflc水平及水平及flc/ flc/ 升高。升高。n上述指標是心肌損傷的標志上述指標是心肌損傷的標志結(jié)論結(jié)論我國心肌病患者我國心肌病患者hcv感染率研究感染率研究心肌病患者心肌病患者hcv感染回顧性研究感染回顧性研究研究對象研究對象北京大學(xué)人民醫(yī)院北京大學(xué)人民醫(yī)院2003年年-2008年心內(nèi)年心內(nèi)

14、科住院的科住院的dcm,hcm患者患者dcm hcm 診斷標準診斷標準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