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1、NAFLD流行情况,Aliment Pharmacol Ther 2011; 34: 274285,NAFLD流行情况Aliment Pharmacol The,1020,2033,1029（10 years）,Science. 2011 June 24; 332(6037): 15191523.,427,102020331029Science.,HBV流行情况,HBV流行情况,HCV流行情况,Liver International (2011)：61-80,HCV流行情况Liver International (20,HCV与NAFLD,HCV与NAFLD,HCV感染者HS患病率及临床特点,
2、HCV感染者HS患病率及临床特点,Angulo P. Archives of Medical Research 2007;38:621-7.,HCV基因分型与肝脂肪变,HCV与NAFLD,Angulo P. Archives of Medical,HCV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,HCV与IR,Cancer 2009;115:565161.,IRS-1 2、 TNF-a、 PI3-K、 Akt、 SREBP,PI3K-Akt信号
3、通路,HCV与IR Cancer 2009;115:565161,HCV病毒蛋白诱导的HE,IR,HCC的机制,HCV病毒蛋白诱导的,NAFLD与CHC肝纤维化,NAFLD与CHC肝纤维化Author, yearPati,病毒性肝炎与完美课课件,HCV与NAFLD,Factors associated with poor response to antiviral therapy in hepatitis C virus,HCV与NAFLDAuthor, yearPatients,NAFLD与SVR,Liver International 2009; 29 (s2): 312,NAFLD与SV
4、RLiver International 2,Romero-Gomez.Gastroenterology 2005; 128: 63641.,Romero-Gomez.Gastroenterology,Aliment Pharmacol Ther 27, 855865,Degree of insulin resistance and effect on EVR and SVR,Aliment Pharmacol Ther 27, 855,TG (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 2
5、4; 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 liver cirrhosis in CHB.Rosuvastatin reduces nonalcoholic fatty liver disease in patients with CHC treated with -interferon and ribavirinHepatic steatosis (0.IRS-1
6、2、 TNF-a、 PI3-K、 Akt、 SREBP中华消化病杂志，2012年HBsAg阳性表达 HBcAg阳性表达of liver cirrhosis in CHB.,HCV与AFLD,Host factors influencing HCV SVR,TG (mmol/L)HCV与AFLDHost factor,细胞激酶信号-3抑制剂,胰岛素受体底物-1,信号转导及转录活化因子,Virus-related mechanisms for decreased SVR,HCV与AFLD,细胞激酶信号-3抑制剂 胰岛素受体底物-1 信号转导及转录活,Pioglitazone with Peg-IF
7、N -2a and RBV in HCV Genotype 1 Patients (Placebo-controlled RCT),Virologic Response (%),Placebo-controlled, double-blind, randomized trial: CHC genotype 1 with HOMA 2 (n = 20 in each group)Pioglitazone 30 mg/day for 48 weeks,Conjeevaram H, et al. AASLD 59th Annual Meeting, San Francisco, CA, 2008,P
8、ioglitazone with Peg-IFN -2a,Metformin with Peg-IFN -2a and RBV in Treatment-nave HCV Genotype 1 Patients with IR (TRIC-1),Virologic Response (%),p = 0.031,Multicenter, randomized trial: CHC genotype 1 with HOMA 2 (n = 125)Metformin 425 mg tid x 4 wks then 850 mg tid x 44 wks,Romero-Gomez M, et al.
9、AASLD 59th Annual Meeting, San Francisco, CA, 2008,Metformin with Peg-IFN -2a an,Rosuvastatin reduces nonalcoholic fatty liver disease in patients with CHC treated with -interferon and ribavirin,Hepat Mon. 2011;11(2):92-98,Conclusions: In HCV patients with NAFLD, the addition of rosuvastatin to inte
10、rferon and ribavirin significantly reduces viremia, steatosis, and fibrosis without causing side effects,Rosuvastatin reduces nonalcoho,Hepatic Steatosis and Hepatitis C co-factor,Hepatic Steatosis and Hepatit,HBV与NAFLD,HBV与NAFLD,葡萄牙学者4100例HBV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
11、，糖尿病等（3）无关因素：转氨酶，HBeAg,基因型，肝组织学等,葡萄牙学者4100例HBV感染者荟萃分析：,HBV与NAFLD,Journal of Gastroenterology and Hepatology 26 (2011) 13611367,HBV与NAFLDJournal of Gastroente,Journal of Gastroenterology and Hepatology 26 (2011) 13611367,HBV与NAFLD,Journal of Gastroenterology an,4%（422/1263）Journal of Gastroenterology
12、 and Hepatology 26 (2011) 13611367Association with HBeAg or HBV DNA? 2 (n = 20 in each group)4%（422/1263）BMI (kg/m2),Journal of Gastroenterology and Hepatology 26 (2011) 13611367,HBV与NAFLD,4%（422/1263）Journal of Gastroe,Steatosis in CHB: lack of associations with HBV replication and disease severity
13、,HBV与NAFLD,Steatosis in CHB: lack of asso,of liver cirrhosis in CHB.,Metabolic syndrome is an independent risk factor of liver cirrhosis in CHB,of liver cirrhosis in CHB.Meta,HBV与NAFLD,Biochem. J. (2008) 416, e15e17,HBV与NAFLDBiochem. J. (2008) 41,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CHB患者对聚乙二醇干扰素
14、治疗的反应较佳，能够长时间保持HBV的低复制状态。Kau A,et al. J Hepatol. 2008 Oct;49(4):634-51,Mehmet Cindoruk,J Clin Gastroenterol,2007,513-517,0%,10%,20%,30%,HBeAg+,40%,肝脂肪变,无肝脂肪变,P0.05,P0.05,39.6,33.3,36.2,31.5,HBeAg -,HBV与NAFLD,肝脂肪变对CHB抗病毒治疗SVR的影响 无肝细胞,影响Peg-IFN抗HBV治疗SVR的因素,Mehmet Cindoruk,MD,et al.J Clin Gastroenterol
15、. 2007,41（ 5）:513-517,影响Peg-IFN抗HBV治疗SVR的因素Mehmet Ci,影响Peg-IFN抗HBV治疗SVR的因素-98wks,SHI JP, EASL/NASH,2009,影响Peg-IFN抗HBV治疗SVR的因素-98wksSHI,我们的工作,我们的工作,CHB患者合并脂肪变性发生率情况33.4%（422/1263）,HBV与NAFLD,宓余强，刘勇钢，徐亮等. 中华肝脏病杂志 2009;第11期,CHB患者合并脂肪变性发生率情况33.4%（422/126,HBV与NAFLD,肝脂肪变组与无脂肪变组CHB患者体重、血脂、血糖的比较,宓余强，刘勇钢，徐亮等.
16、 中华肝脏病杂志 2009;第11期,HBV与NAFLD组 别例数BMI (kg/m2)FPG (,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 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/mlGastroent
17、erology 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.Author, year,HBV与NAFLD,肝脂肪变组与无脂肪变组CHB患者肝功能的比较,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）HBV与NAFLD 肝脂肪变组与无,HBV与NAFLD,肝脂肪变组与无脂肪变组CHB患者血清HBV
18、DNA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,HBV与NAFLD 肝脂肪变组与无脂肪变组CHB患者血清HB,肝脂肪变组与无脂肪变组CHB患者血清HBV DNA滴度的比较,HBV与NAFLD,宓余强，刘勇钢，徐亮等. 中华肝脏病杂志 2009;第11期,2=6.154， P 0.05,肝脂肪变组与无脂肪变组CHB患者血清HBV DNA滴度的比较,HBV与NAFLD,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CHB患者HBV DNA滴度比较（例，%）,HBV-DNA,HBV与NAFLD 宓余强，刘勇钢，徐亮等. 中华
19、肝脏病杂志,不同程度肝脂肪变组CHB患者HBV DNA滴度分层比较（%）,宓余强，刘勇钢，徐亮等. 中华肝脏病杂志 2009;第11期,2=4.941，P0.05,HBV与NAFLD,不同程度肝脂肪变组CHB患者HBV DNA滴度分层比较（%）,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。,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,肝脂肪变组与无脂肪变组患者部分肝脏病理指标的比较（%）,HBV与NAFLD,宓余强，刘勇钢，徐亮等. 中华消化病杂志，
20、2012年,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,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 2-3（网状纤维染色）,HBsAg阳性表达 HBcAg阳性表达,HBsAg阳性表达 HBcAg阳性表达,G 1（HE染色）,S 1（网状纤维染色）,CHB不伴有肝脂肪变（上）及CHB合并肝脂肪变（下）典型病,肝脂肪变影响了CHB患者肝组织内HBsAg、HBcAg的表达，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,肝脂肪变影响了CHB患者肝组织内HBsAg、HBcAg的表达,研究对
21、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。,CHB合并肝脂肪变抗病毒治疗,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,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 2009;第11期TC (mmol/L)Sanyal
22、 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 (0.02 in genotype 3)Conclusions: In HCV patients with NAFLD, the addition of rosuvastatin to interferon and ribavirin significantly reduces viremia, steatosis, and fibrosis without causing side effectsFactors associated
23、with advanced fibrosis in hepatitis C virus并存的肝脂肪变对乙型肝炎患者肝损伤可能无不良影响；肝脂肪变对CHB抗病毒治疗SVR的影响（1）HS患病率：29.Metabolic syndrome is an independent risk factor,两组应用PEG-INF -2a抗乙肝病毒疗效比较n（%）,P0.05,Kau A,et al.两组应用PEG-INF -2a抗乙,两组应用PEG-INF-2a抗乙肝病毒疗效应答率比较（%）,P0.05,两组应用PEG-INF-2a抗乙肝病毒疗效应答率比较（%）,PEG-INF -2a抗乙肝病毒治疗48周
24、与治疗前血脂变化比较,较治疗前比较，P0.05。,PEG-INF -2a抗乙肝病毒治疗48周与治疗前血脂变化,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。,结论此次研究未发现轻度肝脂肪变对PEG-INF -2a抗H,Hepatic Steatosis and Hepatitis Bco-factor or bystander?,Hepatic Steatosis and Hepatiti,谢谢,谢谢,HCV与NAFLD,HCV与NAFLD,of liver cirrhosis in CHB.
25、,Metabolic syndrome is an independent risk factor of liver cirrhosis in CHB,of liver cirrhosis in CHB.Meta,CHB患者合并脂肪变性发生率情况33.4%（422/1263）,HBV与NAFLD,宓余强，刘勇钢，徐亮等. 中华肝脏病杂志 2009;第11期,CHB患者合并脂肪变性发生率情况33.4%（422/126,HBV与NAFLD,肝脂肪变组与无脂肪变组CHB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,HBV与NAFLD组 别例数BMI (kg
26、/m2)FPG (, 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 (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
27、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 International (2011)：61-80中华肝脏病杂志 2009;第11期4%（422/1263）Sanyal 2003Author, year,HBV与NAFLD,肝脂肪变组与无脂肪变组CHB患者血清HBV DNA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, 1
28、05 拷贝/mlHBV与NAFLD 肝脂肪变组与无脂肪,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 2-3（网状纤维染色）,HBsAg阳性表达 HBcAg阳性表达,HBsAg阳性表达 HBcAg阳性表达,G 1（HE染色）,S 1（网状纤维染色）,CHB不伴有肝脂肪变（上）及CHB合并肝脂肪变（下）典型病,两组应用PEG-INF -2a抗乙肝病毒疗效比较n（%）,P0.05,两组应用PEG-INF -2a抗乙肝病毒疗效比较n（%）组,Association 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,谢谢,Association with HBeAg or HBV,
