病毒性肝炎与NAFL.ppt
,Hepatic Steatosis and Viral Hepatitis co-factor or bystander?,宓余强 天津市传染病医院 天津市肝病医学研究所,NAFLD流行情况,Aliment Pharmacol Ther 2011;34:274285,1020,2033,1029（10 years）,Science.2011 June 24;332(6037):15191523.,427,HBV流行情况,2009年天津市肝病年会,HCV流行情况,2009年天津市肝病年会,Liver International(2011)：61-80,HCV与NAFLD,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,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与IR,Cancer 2009;115:565161.,IRS-1 2、TNF-a、PI3-K、Akt、SREBP,PI3K-Akt信号通路,HCV病毒蛋白诱导的HE,IR,HCC的机制,NAFLD与CHC肝纤维化,HCV与NAFLD,Factors associated with poor response to antiviral therapy in hepatitis C virus,NAFLD与SVR,Liver International 2009;29(s2):312,Romero-Gomez.Gastroenterology 2005;128:63641.,Aliment Pharmacol Ther 27,855865,Degree of insulin resistance and effect on EVR and SVR,HCV与AFLD,Host factors influencing HCV SVR,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,Pioglitazone with Peg-IFN-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,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.AASLD 59th Annual Meeting,San Francisco,CA,2008,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 interferon and ribavirin significantly reduces viremia,steatosis,and fibrosis without causing side effects,Hepatic Steatosis and Hepatitis C co-factor,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，糖尿病等（3）无关因素：转氨酶，HBeAg,基因型，肝组织学等,HBV与NAFLD,Journal of Gastroenterology and Hepatology 26(2011)13611367,Journal of Gastroenterology and Hepatology 26(2011)13611367,HBV与NAFLD,Journal of Gastroenterology and Hepatology 26(2011)13611367,HBV与NAFLD,Steatosis in CHB:lack of associations with HBV replication and disease severity,HBV与NAFLD,of liver cirrhosis in CHB.,Metabolic syndrome is an independent risk factor of liver cirrhosis in CHB,HBV与NAFLD,Biochem.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CHB患者对聚乙二醇干扰素治疗的反应较佳，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,影响Peg-IFN抗HBV治疗SVR的因素,Mehmet Cindoruk,MD,et al.J Clin Gastroenterol.2007,41（5）:513-517,影响Peg-IFN抗HBV治疗SVR的因素-98wks,SHI 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%（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,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,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,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,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,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,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,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（%）,HBV与NAFLD,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 2-3（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）,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,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。,CHB合并肝脂肪变抗病毒治疗,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抗乙肝病毒疗效应答率比较（%）,P0.05,PEG-INF-2a抗乙肝病毒治疗48周与治疗前血脂变化比较,较治疗前比较，P0.05。,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?,谢谢,
