病毒性肝炎与完美课课件.pptx

1、NAFLD流行情况Aliment Pharmacol Ther 2011;34:274285101020202020333310102929（10 years10 years）Science.2011 June 24;332(6037):15191523.4 42727HBV流行情况HCV流行情况Liver International(2011)：61-80HCVHCV与NAFLDNAFLDHCV感染者感染者HS患病率及临床特点患病率及临床特点Angulo P.Archives of Medical Research 2007;38:621-7.HCVHCV基因分型与肝脂肪变基因分型与肝脂肪变

2、3型1型/4型检出率70%30%危险因素HCV-RNA肥胖和IR加剧肝损伤是是降低SVR否是SVR后脂肪变消退有所减轻?减肥后脂肪变有所减轻？消退HCVHCV与与NAFLDNAFLDHCV病毒蛋白诱导的脂代谢紊乱的机制病毒蛋白诱导的脂代谢紊乱的机制固醇调节元件结合蛋白 微粒体三酰甘油转移蛋白 过氧化体增殖剂激活的受体 蛋白酶体激活剂PA28亚单位 HCV与IR Cancer 2009;115:565161.IRS-1 2、TNF-a、PI3-K、Akt、SREBPPI3K-AktPI3K-Akt信号通路信号通路HCV病毒蛋白诱导的病毒蛋白诱导的HE,IR,HCC的机制的机制 NAFLDNAFL

3、D与与CHCCHC肝纤维化肝纤维化Author,yearAuthor,yearPatients Patients(n)(n)Characteristics associated with fibrosis(Characteristics associated with fibrosis(P P)Cross 2009Cross 2009122122Hepatic steatosis(0.006)Hepatic steatosis(0.006)Hourigan 2004Hourigan 2004148148Hepatic steatosis(0.03)Hepatic steatosis(0.03)

4、Adinolfi 2001Adinolfi 2001180180Hepatic steatosis(0.001),age(0.001)Hepatic steatosis(0.001),age(0.001)Hui 2003Hui 2003260260HOMA-IR(0.001)HOMA-IR(0.001)Poynard 2003Poynard 200314281428Hepatic steatosis(0.007)Hepatic steatosis(0.007)Ratziu 2003Ratziu 2003710710Hyperglycemia(0.01),BMI(0.01),Hyperglyce

5、mia(0.01),BMI(0.01),steatosis(0.01)steatosis(0.01)Sanyal 2003Sanyal 2003144144BMI(0.003),cytologic ballooning(0.003),BMI(0.003),cytologic ballooning(0.003),diabetes(0.03)diabetes(0.03)Younossi 2004Younossi 2004120120Superimposed NASH(0.001)Superimposed NASH(0.001)Rubbia-Brandt Rubbia-Brandt 20042004

6、755755Hepatic steatosis(0.001 in genotype 3)Hepatic steatosis(30 kg/mBMI30 kg/m2 2(0.01),cirrhosis(0.01),0.01),cirrhosis(0.01),genotype 1(0.01)genotype 1(0.01)Poynard 2003Poynard 200314281428BMI,hepatic steatosis(0.001)BMI,hepatic steatosis(0.001)Sanyal 2003Sanyal 2003144144Presence of NAFLD(0.01)Pr

7、esence of NAFLD(33%(0.001)Steatosis33%(0.001)Factors associated with poor response to antiviral therapy in hepatitis C virusFactors associated with poor response to antiviral therapy in hepatitis C virusNAFLDNAFLD与与SVRSVRLiver International 2009;29(s2):312Romero-Gomez.Gastroenterology 2005;128:63641

8、.Aliment Pharmacol Ther 27,855865Degree of insulin resistance and effect on EVR and SVRTG(mmol/L)中华肝脏病杂志 2009;第11期影响Peg-IFN抗HBV治疗SVR的因素-98wksYounossi 20042011 June 24;332(6037):15191523.HCV感染者HS患病率及临床特点Younossi 2004 105 拷贝/mlPatients(n)S 2-3（网状纤维染色）中华消化病杂志，2012年steatosis(0.Hepatic steatosis(0.of liv

9、er cirrhosis in CHB.Rosuvastatin reduces nonalcoholic fatty liver disease in patients with CHC treated with-interferon and ribavirinHepatic steatosis(2(n=20 in each group)Pioglitazone 30 mg/day for 48 weeksConjeevaram H,et al.AASLD 59th Annual Meeting,San Francisco,CA,2008 Metformin with Peg-IFN-2a

10、and RBV in Treatment-nave HCV Genotype 1 Patients with IR(TRIC-1)Virologic Response(%)p=0.031Multicenter,randomized trial:CHC genotype 1 with HOMA 2(n=125)Metformin 425 mg tid x 4 wks then 850 mg tid x 44 wksRomero-Gomez M,et al.AASLD 59th Annual Meeting,San Francisco,CA,2008 Rosuvastatin reduces no

11、nalcoholic fatty liver disease in patients with CHC treated with-interferon and ribavirinHepat Mon.2011;1111(2):92-98Conclusions:In HCV patients with NAFLD,the addition of rosuvastatin to interferon and ribavirin significantly reduces viremia,steatosis,and fibrosis without causing side effectsHepati

12、c Steatosis and Hepatitis C co-factorHBVHBV与NAFLDNAFLD葡萄牙学者4100例例HBV感染者感染者荟萃分析：（1）HS患病率：29.6%（普通人群类似，低于HCV感染者）（2）高危因素：男性，BMI,肥胖，糖尿病等（3）无关因素：转氨酶，HBeAg,基因型，肝组织学等HBVHBV与与NAFLDNAFLDJournal of Gastroenterology and Hepatology 26(2011)13611367Journal of Gastroenterology and Hepatology 26(2011)13611367HBVHB

13、V与与NAFLDNAFLD4%（422/1263）Journal of Gastroenterology and Hepatology 26(2011)13611367Association with HBeAg or HBV DNA?103 拷贝/mlIRS-1 2、TNF-a、PI3-K、Akt、SREBP宓余强，刘勇钢，徐亮等.肝脂肪变组与无脂肪变组CHB患者血清HBV DNA滴度的比较Superimposed NASH(0.中华肝脏病杂志 2009;第11期过氧化体增殖剂激活的受体Poynard 2003不同程度肝脂肪变组CHB患者HBV DNA滴度比较（例，%）HBsAg阳性表达 H

14、BcAg阳性表达中华肝脏病杂志 2009;第11期宓余强，刘勇钢，徐亮等.steatosis(2(n=20 in each group)4%（422/1263）BMI(kg/m2)Journal of Gastroenterology and Hepatology 26(2011)13611367HBVHBV与与NAFLDNAFLDSteatosis in CHB:lack of associations with HBV replication and disease severityAuthorsAssociation with HBeAg or HBV DNA?Worsens fibro

15、sis severity?Elloumi et al.2008Shi et al.2008Peng et al.2008Yun et al.2009Kumar et al.2009Minakari et al.2009Persico et al.2009Wong GL et al.2009NoNoNoNoNoNoNot mentionedNot mentionedNo NoNoNoNoNoNoYesHBVHBV与与NAFLDNAFLDo of f l li iv ve er r c ci ir rr rh ho os si is s i in n C CH HB B.Metabolic syn

16、drome is an independent risk factor Metabolic syndrome is an independent risk factor of liver cirrhosis in CHBof liver cirrhosis in CHB HBVHBV与与NAFLDNAFLDBiochem.J.(2008)416,e15e17肝脂肪变对CHB抗病毒治疗SVR的影响 无肝细胞脂肪变性或仅发生局限性脂肪变性的无肝细胞脂肪变性或仅发生局限性脂肪变性的CHBCHB患者对聚乙二醇干患者对聚乙二醇干扰素治疗的反应较佳，能够长时间保持扰素治疗的反应较佳，能够长时间保持HBVH

17、BV的低复制状态。的低复制状态。Kau A,et al.J Hepatol.2008 Oct;49(4):634-51Mehmet Cindoruk,J Clin Gastroenterol,2007,513-5170%10%20%30%HBeAg+HBeAg+40%肝脂肪变肝脂肪变无肝脂肪变无肝脂肪变P0.05P0.05P0.05P0.0539.639.633.333.336.236.231.531.5HBeAg-HBeAg-HBVHBV与与NAFLDNAFLD影响影响Peg-IFN抗抗HBV治疗治疗SVR的因素的因素Mehmet Cindoruk,MD,et al.J Clin Gastr

18、oenterol.2007,41（5）:513-517影响影响Peg-IFN抗抗HBV治疗治疗SVR的因素的因素-98wksSHI JP,EASL/NASH,2009我们的工作CHB患者合并脂肪变性发生率情况33.4%33.4%（422/1263422/1263）HBVHBV与与NAFLDNAFLD宓余强，刘勇钢，徐亮等.中华肝脏病杂志 2009;第11期HBVHBV与与NAFLDNAFLD组 别例数BMI(kg/m2)FPG(mmol/L)TG(mmol/L)TC(mmol/L)肝脂肪变组11425.133.355.391.241.581.044.591.26无肝脂肪变组11321.993.

19、144.910.881.200.474.161.04t值6.8112.7333.0632.340P值 0.01 0.01 0.01 0.05 肝脂肪变组与无脂肪变组肝脂肪变组与无脂肪变组CHBCHB患者体重、血脂、血糖的比较患者体重、血脂、血糖的比较 宓余强，刘勇钢，徐亮等.中华肝脏病杂志 2009;第11期S 2-3（网状纤维染色）Host factors influencing HCV SVR两组应用PEG-INF-2a抗乙肝病毒疗效比较n（%）宓余强，刘勇钢，徐亮等.Poynard 2003PEG-INF-2a抗乙肝病毒治疗48周与治疗前血脂变化比较中华肝脏病杂志 2009;第11期of

20、 liver cirrhosis in CHB.Conjeevaram H,et al.肝脂肪变组与无脂肪变组患者部分肝脏病理指标的比较（%）Poynard 2003 105 拷贝/mlGastroenterology 2005;128:63641.Patients(n)02 in genotype 3)Sanyal 2003过氧化体增殖剂激活的受体Factors associated with advanced fibrosis in hepatitis C virusSuperimposed NASH(0.05 0.05 0.05 0.05 0.05HBVHBV与与NAFLDNAFLD 肝

21、脂肪变组与无脂肪变组肝脂肪变组与无脂肪变组CHBCHB患者血清患者血清HBV DNAHBV DNA滴度的比较（例，滴度的比较（例，%）宓余强，刘勇钢，徐亮等.中华肝脏病杂志 2009;第11期组 别例数 105 拷贝/ml肝脂肪变组10127（26.7%）15（14.9%）59（58.4%）无肝脂肪变组9512（12.6%）18（18.9%）65（68.4%）2值6.154P值 0.05HBV-DNA肝脂肪变组与无脂肪变组肝脂肪变组与无脂肪变组CHBCHB患者血清患者血清HBV DNAHBV DNA滴度的比较滴度的比较HBVHBV与与NAFLDNAFLD宓余强，刘勇钢，徐亮等.中华肝脏病杂志

22、2009;第11期2=6.154，P 0.05HBVHBV与与NAFLDNAFLD 宓余强，刘勇钢，徐亮等.中华肝脏病杂志 2009;第11期不同程度肝脂肪变组不同程度肝脂肪变组CHBCHB患者患者HBV DNAHBV DNA滴度比较（例，滴度比较（例，%）组 别 105 拷贝/ml 105 拷贝/ml轻度肝脂肪变组29（35.4%）53（64.6%）中重度脂肪变组12（63.2%）7（36.8%）2值4.941P值0.05HBV-DNA不同程度肝脂肪变组不同程度肝脂肪变组CHBCHB患者患者HBV DNAHBV DNA滴度分层比较（滴度分层比较（%）宓余强，刘勇钢，徐亮等.中华肝脏病杂志 2

23、009;第11期2=4.941，P0.05HBVHBV与与NAFLDNAFLD结论慢性乙型肝炎合并肝脂肪变常见且不断增多，主要与代谢紊乱有关；并存的肝脂肪变对乙型肝炎患者肝损伤可能无不良影响；HBV DNA滴度是否与肝脂肪变呈负相关有待进一步验证。肝脂肪变组与无脂肪变组患者部分肝脏病理指标的比较（肝脂肪变组与无脂肪变组患者部分肝脏病理指标的比较（%）组 别例数中重度炎症明显肝纤维化 HBsAg染色强阳性 HBcAg染色强阳性无脂肪变组14745（30.6%）39（26.5%）34（23.1%）21（14.3%）肝脂肪变组14923（15.4%）19（12.8%）10（6.7%）16（10.7%

24、）2值9.6318.91715.7610.851P值 0.01 0.01 0.05HBVHBV与与NAFLDNAFLD宓余强，刘勇钢，徐亮等.中华消化病杂志，2012年 CHB不伴有肝脂肪变（上）及CHB合并肝脂肪变（下）典型病例病理形态特征 G 3（HE染色）S 2-3S 2-3（网状纤维染色）（网状纤维染色）HBsAg HBsAg阳性表达阳性表达 HBcAgHBcAg阳性表达阳性表达 HBsAgHBsAg阳性表达阳性表达 HBcAgHBcAg阳性表达阳性表达G 1G 1（HEHE染色）染色）S 1S 1（网状纤维染色）（网状纤维染色）肝脂肪变影响了CHB患者肝组织内HBsAg、HBcAg的

25、表达，随肝脂肪变的出现及加重，其表达呈下降趋势；肝脂肪变与其肝组织学损伤程度较轻相一致。结论研究对象：天津市传染病医院经肝组织病理检查确诊为慢性乙型肝炎、且进行PEG-INF-2a抗病毒治疗的患者50例，其中男性40例，女性10例；无脂变组：28例；脂变组：22例，其中轻度脂肪变21例，中度脂肪变1例。CHBCHB合并肝脂肪变抗病毒治疗合并肝脂肪变抗病毒治疗Kau A,et al.中华肝脏病杂志 2009;第11期Metabolic syndrome is an independent risk factorLiver International 2009;29(s2):312中华肝脏病杂志

26、2009;第11期TC(mmol/L)Sanyal 2003过氧化体增殖剂激活的受体HCV基因分型与肝脂肪变4%（422/1263）Author,year003),cytologic ballooning(0.05P0.05两组应用PEG-INF-2a抗乙肝病毒疗效应答率比较（%）P0.05P0.05PEG-INF-2a抗乙肝病毒治疗48周与治疗前血脂变化比较CHOCHO（mmol/Lmmol/L）TGTG（mmol/Lmmol/L）治疗前治疗前治疗后治疗后治疗前治疗前治疗后治疗后无脂变组（无脂变组（2828例）例）4.224.220.630.634.664.661.761.761.111.1

27、10.500.501.331.330.570.57有脂变组（有脂变组（2222例）例）4.294.291.111.113.993.990.510.511.251.250.520.522.302.301.921.92较治疗前比较，较治疗前比较，P0.05P0.05P0.05。结论此次研究未发现轻度肝脂肪变对PEG-INF-2a抗HBV治疗的疗效有明显影响。肝脂肪变组PEG-INF-2a抗HBV治疗中总胆固醇下降。Hepatic Steatosis and Hepatitis Bco-factor or bystander?HCVHCV与NAFLDNAFLDo of f l li iv ve er

28、 r c ci ir rr rh ho os si is s i in n C CH HB B.Metabolic syndrome is an independent risk factor Metabolic syndrome is an independent risk factor of liver cirrhosis in CHBof liver cirrhosis in CHB CHB患者合并脂肪变性发生率情况33.4%33.4%（422/1263422/1263）HBVHBV与与NAFLDNAFLD宓余强，刘勇钢，徐亮等.中华肝脏病杂志 2009;第11期HBVHBV与与NAFL

29、DNAFLD组 别例数BMI(kg/m2)FPG(mmol/L)TG(mmol/L)TC(mmol/L)肝脂肪变组11425.133.355.391.241.581.044.591.26无肝脂肪变组11321.993.144.910.881.200.474.161.04t值6.8112.7333.0632.340P值 0.01 0.01 0.01 105 拷贝/mlSuperimposed NASH(0.影响Peg-IFN抗HBV治疗SVR的因素-98wksPoynard 2003过氧化体增殖剂激活的受体Journal of Gastroenterology and Hepatology 26

30、(2011)13611367HCV基因分型与肝脂肪变Metformin with Peg-IFN-2a and RBV in Treatment-nave HCV Genotype 1 Patients with IR(TRIC-1)Metabolic syndrome is an independent risk factor中华肝脏病杂志 2009;第11期肝脂肪变组与无脂肪变组CHB患者体重、血脂、血糖的比较肝脂肪变对CHB抗病毒治疗SVR的影响Kau A,et al.2011 June 24;332(6037):15191523.Conjeevaram H,et al.Liver In

31、ternational(2011)：61-80中华肝脏病杂志 2009;第11期4%（422/1263）Sanyal 2003Author,yearHBVHBV与与NAFLDNAFLD 肝脂肪变组与无脂肪变组肝脂肪变组与无脂肪变组CHBCHB患者血清患者血清HBV DNAHBV DNA滴度的比较（例，滴度的比较（例，%）宓余强，刘勇钢，徐亮等.中华肝脏病杂志 2009;第11期组 别例数 105 拷贝/ml肝脂肪变组10127（26.7%）15（14.9%）59（58.4%）无肝脂肪变组9512（12.6%）18（18.9%）65（68.4%）2值6.154P值0.05P0.05Association with HBeAg or HBV DNA?信号转导及转录活化因子of liver cirrhosis in CHB.Younossi 2004 105 拷贝/mlKumar et al.Placebo-controlled,double-blind,randomized trial:CHC genotype 1 with HOMA 2(n=20 in each group)105 拷贝/mlHepatic steatosis(30 kg/m2(0.HBsAg阳性表达 HBcAg阳性表达