病毒性肝炎與NAFLD課件

HepaticSteatosisandViralHepatitis

co-factororbystander?宓余強天津市傳染病醫(yī)院天津市肝病醫(yī)學(xué)研究所病毒性肝炎與NAFLDNAFLD流行情況AlimentPharmacolTher2011;34:274–285病毒性肝炎與NAFLD10％～20％20％～33％10％～29％（10years）Science.2011June24;332(6037):1519–1523.4％～27％病毒性肝炎與NAFLDHBV流行情況病毒性肝炎與NAFLDHCV流行情況LiverInternational(2011)：61-80病毒性肝炎與NAFLDHCV與NAFLD病毒性肝炎與NAFLDHCV感染者HS患病率及臨床特點病毒性肝炎與NAFLDAnguloP.ArchivesofMedicalResearch2007;38:621-7.HCV基因分型與肝脂肪變3型1型/4型檢出率～70%>30%危險因素HCV-RNA肥胖和IR加劇肝損傷是是降低SVR否是SVR后脂肪變消退有所減輕?減肥后脂肪變有所減輕？消退HCV與NAFLD病毒性肝炎與NAFLDHCV病毒蛋白誘導(dǎo)的脂代謝紊亂的機制固醇調(diào)節(jié)元件結(jié)合蛋白

微粒體三酰甘油轉(zhuǎn)移蛋白

過氧化體增殖劑激活的受體

蛋白酶體激活劑PA28β亞單位

病毒性肝炎與NAFLDHCV與IRCancer2009;115:5651–61.

IRS-1?2、TNF-a、PI3-K、Akt、SREBPPI3K-Akt信號通路病毒性肝炎與NAFLDHCV病毒蛋白誘導(dǎo)的HE,IR,HCC的機制

病毒性肝炎與NAFLDNAFLD與CHC肝纖維化

Author,yearPatients(n)Characteristicsassociatedwithfibrosis(P)Cross2009122Hepaticsteatosis(0.006)Hourigan2004148Hepaticsteatosis(<0.03)Adinolfi2001180Hepaticsteatosis(<0.001),age(<0.001)Hui2003260HOMA-IR(<0.001)Poynard20031428Hepaticsteatosis(0.007)Ratziu2003710Hyperglycemia(<0.01),BMI(<0.01),steatosis(<0.01)Sanyal2003144BMI(<0.003),cytologicballooning(<0.003),diabetes(<0.03)Younossi2004120SuperimposedNASH(<0.001)Rubbia-Brandt2004755Hepaticsteatosis(<0.001ingenotype3)Bugianesi2006132HOMA-IR(0.02ingenotype3)FactorsassociatedwithadvancedfibrosisinhepatitisCvirus病毒性肝炎與NAFLD病毒性肝炎與NAFLDHCV與NAFLDAuthor,yearPatients(n)Characteristicsassociatedwithnonresponse(P)Akuta2002394Hepaticsteatosis,genotype1(n/a)Bressler2003174BMI>30kg/m2(<0.01),cirrhosis(<0.01),genotype1(<0.01)Poynard20031428BMI,hepaticsteatosis(<0.001)Sanyal2003144PresenceofNAFLD(<0.01)Patton2004574Genotype1(0.02)Harrison2005231Steatosis>33%(0.001)FactorsassociatedwithpoorresponsetoantiviraltherapyinhepatitisCvirus病毒性肝炎與NAFLDNAFLD與SVRLiverInternational2009;29(s2):3–12病毒性肝炎與NAFLDRomero-Gomez.Gastroenterology2005;128:636–41.病毒性肝炎與NAFLDAlimentPharmacolTher27,855–865DegreeofinsulinresistanceandeffectonEVRandSVR病毒性肝炎與NAFLDHCV與AFLDHostfactorsinfluencingHCVSVR病毒性肝炎與NAFLD細胞激酶信號-3抑制劑

胰島素受體底物-1信號轉(zhuǎn)導(dǎo)及轉(zhuǎn)錄活化因子

Virus-relatedmechanismsfordecreasedSVRHCV與AFLD病毒性肝炎與NAFLDPioglitazonewithPeg-IFNα-2aandRBVinHCVGenotype1Patients(Placebo-controlledRCT)VirologicResponse(%)Placebo-controlled,double-blind,randomizedtrial:CHCgenotype1withHOMA>2(n=20ineachgroup)Pioglitazone30mg/dayfor48weeksConjeevaramH,etal.AASLD59thAnnualMeeting,SanFrancisco,CA,2008病毒性肝炎與NAFLDMetforminwithPeg-IFNα-2aandRBVinTreatment-na?veHCVGenotype1PatientswithIR(TRIC-1)VirologicResponse(%)p=0.031Multicenter,randomizedtrial:CHCgenotype1withHOMA>2(n=125)Metformin425mgtidx4wksthen850mgtidx44wksRomero-GomezM,etal.AASLD59thAnnualMeeting,SanFrancisco,CA,2008病毒性肝炎與NAFLDRosuvastatinreducesnonalcoholicfattyliverdiseaseinpatientswithCHCtreatedwithα-interferonandribavirinHepatMon.2011;11(2):92-98Conclusions:InHCVpatientswithNAFLD,theadditionofrosuvastatintointerferonandribavirinsignificantlyreducesviremia,steatosis,andfibrosiswithoutcausingsideeffects病毒性肝炎與NAFLDHepaticSteatosisandHepatitisC

co-factor病毒性肝炎與NAFLDHBV與NAFLD病毒性肝炎與NAFLD葡萄牙學(xué)者4100例HBV感染者薈萃分析：（1）HS患病率：29.6%（普通人群類似，低于HCV感染者）（2）高危因素：男性，BMI,肥胖，糖尿病等（3）無關(guān)因素：轉(zhuǎn)氨酶，HBeAg,基因型，肝組織學(xué)等病毒性肝炎與NAFLDHBV與NAFLDJournalofGastroenterologyandHepatology26(2011)1361–1367病毒性肝炎與NAFLDJournalofGastroenterologyandHepatology26(2011)1361–1367HBV與NAFLD病毒性肝炎與NAFLDJournalofGastroenterologyandHepatology26(2011)1361–1367HBV與NAFLD病毒性肝炎與NAFLDSteatosisinCHB:lackofassociationswithHBVreplicationanddiseaseseverityAuthorsAssociationwithHBeAgorHBVDNA?Worsensfibrosisseverity?Elloumietal.2008Shietal.2008Pengetal.2008Yunetal.2009Kumaretal.2009Minakarietal.2009Persicoetal.2009WongGLetal.2009NoNoNoNoNoNoNotmentionedNotmentionedNoNoNoNoNoNoNoYesHBV與NAFLD病毒性肝炎與NAFLDoflivercirrhosisinCHB.MetabolicsyndromeisanindependentriskfactoroflivercirrhosisinCHB

病毒性肝炎與NAFLDHBV與NAFLDBiochem.J.(2008)416,e15–e17病毒性肝炎與NAFLD肝脂肪變對CHB抗病毒治療SVR的影響

無肝細胞脂肪變性或僅發(fā)生局限性脂肪變性的CHB患者對聚乙二醇干擾素治療的反應(yīng)較佳，能夠長時間保持HBV的低復(fù)制狀態(tài)。KauA,etal.JHepatol.2008Oct;49(4):634-51MehmetCindoruk,JClinGastroenterol,2007,513-5170%10%20%30%HBeAg+40%肝脂肪變無肝脂肪變P>0.05P>0.0539.633.336.231.5HBeAg-

HBV與NAFLD病毒性肝炎與NAFLD影響Peg-IFN抗HBV治療SVR的因素MehmetCindoruk,MD,etal.JClinGastroenterol.2007,41（5）:513-517病毒性肝炎與NAFLD影響Peg-IFN抗HBV治療SVR的因素-98wksSHIJP,EASL/NASH,2009病毒性肝炎與NAFLD我們的工作病毒性肝炎與NAFLDCHB患者合并脂肪變性發(fā)生率情況

33.4%（422/1263）HBV與NAFLD宓余強，劉勇鋼，徐亮等.中華肝臟病雜志2009;第11期病毒性肝炎與NAFLDHBV與NAFLD組別例數(shù)BMI(kg/m2)FPG(mmol/L)TG(mmol/L)TC(mmol/L)肝脂肪變組11425.13±3.355.39±1.241.58±1.044.59±1.26無肝脂肪變組11321.99±3.144.91±0.881.20±0.474.16±1.04t值6.8112.7333.0632.340P值<0.01<0.01<0.01<0.05

肝脂肪變組與無脂肪變組CHB患者體重、血脂、血糖的比較

宓余強，劉勇鋼，徐亮等.中華肝臟病雜志2009;第11期病毒性肝炎與NAFLDHBV與NAFLD

肝脂肪變組與無脂肪變組CHB患者肝功能的比較

宓余強，劉勇鋼，徐亮等.中華肝臟病雜志2009;第11期組別例數(shù)ALTASTGGTALPTBiL肝脂肪變組11492.6±105.156.0±56.755.5±49.8104.9±76.720.0±26.1無肝脂肪變組11382.9±81.647.2±29.455.7±50.6117.3±71.716.3±7.8t值0.7441.390-0.029-1.1751.393P值>0.05>0.05>0.05>0.05>0.05病毒性肝炎與NAFLDHBV與NAFLD

肝脂肪變組與無脂肪變組CHB患者血清HBVDNA滴度的比較（例，%）宓余強，劉勇鋼，徐亮等.中華肝臟病雜志2009;第11期組別例數(shù)<103拷貝/ml103～105拷貝/ml

>105拷貝/ml肝脂肪變組10127（26.7%）15（14.9%）59（58.4%）無肝脂肪變組9512（12.6%）18（18.9%）65（68.4%）χ2值6.154P值<0.05HBV-DNA病毒性肝炎與NAFLD肝脂肪變組與無脂肪變組CHB患者血清HBVDNA滴度的比較HBV與NAFLD宓余強，劉勇鋼，徐亮等.中華肝臟病雜志2009;第11期Χ2=6.154，P<0.05病毒性肝炎與NAFLDHBV與NAFLD

宓余強，劉勇鋼，徐亮等.中華肝臟病雜志2009;第11期不同程度肝脂肪變組CHB患者HBVDNA滴度比較（例，%）組別

<105拷貝/ml≥105拷貝/ml輕度肝脂肪變組29（35.4%）53（64.6%）中重度脂肪變組12（63.2%）7（36.8%）χ2值4.941P值<0.05HBV-DNA病毒性肝炎與NAFLD不同程度肝脂肪變組CHB患者HBVDNA滴度分層比較（%）宓余強，劉勇鋼，徐亮等.中華肝臟病雜志2009;第11期Χ2=4.941，P<0.05HBV與NAFLD病毒性肝炎與NAFLD結(jié)論慢性乙型肝炎合并肝脂肪變常見且不斷增多，主要與代謝紊亂有關(guān)；并存的肝脂肪變對乙型肝炎患者肝損傷可能無不良影響；HBVDNA滴度是否與肝脂肪變呈負相關(guān)有待進一步驗證。病毒性肝炎與NAFLD肝脂肪變組與無脂肪變組患者部分肝臟病理指標的比較（%）組別例數(shù)中重度炎癥明顯肝纖維化HBsAg染色強陽性HBcAg染色強陽性無脂肪變組14745（30.6%）39（26.5%）34（23.1%）21（14.3%）肝脂肪變組14923（15.4%）19（12.8%）10（6.7%）16（10.7%）χ2值9.6318.91715.7610.851P值<0.01<0.01<0.001>0.05HBV與NAFLD宓余強，劉勇鋼，徐亮等.中華消化病雜志，2012年病毒性肝炎與NAFLD

CHB不伴有肝脂肪變（上）及CHB合并肝脂肪變（下）典型病例病理形態(tài)特征G3（HE染色）S2-3（網(wǎng)狀纖維染色）

HBsAg陽性表達HBcAg陽性表達

HBsAg陽性表達HBcAg陽性表達G1（HE染色）

S1（網(wǎng)狀纖維染色）

病毒性肝炎與NAFLD肝脂肪變影響了CHB患者肝組織內(nèi)HBsAg、HBcAg的表達，隨肝脂肪變的出現(xiàn)及加重，其表達呈下降趨勢；肝脂肪變與其肝組織學(xué)損傷程度較輕相一致。結(jié)論病毒性肝炎與NAFLD研究對象：天津市傳染病醫(yī)院經(jīng)肝組織病理檢查確診為慢性乙型肝炎、