病毒性肝炎合并脂肪肝的治疗策略PPT课件

病毒性肝炎合并脂肪肝的治疗策略NP-ESS-20170118-3 1目 录 病毒性肝炎合并脂肪肝的流行病学 慢性乙型肝炎合并脂肪肝的危害和治疗策略 慢性丙型肝炎合并脂肪肝的危害和治疗策略2全球和中国肝病的病因分布Wang FS, et al. Hepatology. 2014 ;60(6):2099-108HBV感染和脂肪肝是我国最主要的肝病病因。314%-71%的慢乙肝患者合并脂肪肝Raluca Pais, et al. Clin Liver Dis 18 (2014) 165178欧洲和中东地区 亚太地区440-86%的慢性丙型肝炎患者合并脂肪肝T Asselah, et al. Gut 2006;55:123130 5中国慢性乙型肝炎和慢性丙型肝炎患者脂肪肝的流行情况Raluca Pais, et al. Clin Liver Dis 18 (2014) 165178 6合并脂肪肝对慢性病毒性肝炎患者临床预后的影响肝硬化风险肝细胞癌风险范建高 . 中华肝脏病杂志 ; 2009;17(11):801-805 7问 题 如何正确理解病毒肝与脂肪肝之间的关系？ 如何治疗病毒肝合并脂肪肝的患者？病毒性肝炎（乙型、丙型） 脂肪肝 ？病毒性肝炎（乙型、丙型） + 脂肪肝 ？以治疗脂肪肝为主？ 以治疗病毒肝为主？双管齐下？8目 录 病毒性肝炎合并脂肪肝的流行病学 慢性乙型肝炎合并脂肪肝的危害和治疗策略 慢性丙型肝炎合并脂肪肝的危害和治疗策略9肝脏在肥胖相关并发症发病机制中的关键角色Thomas Karlas, et al. Best Practice 27:195208 10HBV 感染与代谢综合征：事实还是虚构？Chia-Chi Wang, et al. J Gastroenterol Hepatol. 2014 Aug 5. doi: 10.1111/jgh.12700. Epub ahead of print 11HBV感染与代谢综合征的相互关系：临床研究汇总研究设计 样本量 结果Jarcuska P Cross-section 855 A higher viral load in patient of chronic HBV infection with metabolic syndrome than those without.Chung TH Cross-section 9474 HBV infection was negatively associatedwith metabolic syndrome in men.Jinjuvadia RLarge population databaseChronicHBV: pastexposure toHBV=593594:7280620Chronic HBV infection was inversely associatedwith metabolic syndromeLi WC2013Case series 26305 The prevalence of metabolic syndromewas not different between HBV and non-HBV patientsLi X2012Case series 138 Metabolic syndrome in HBV patientscorrelated with insulin resistance and less effect of virusWong VW2012Case series 1013 HBV infection is associated with lower prevalence of metabolic syndrome than controls (11% vs. 20.2%; p=0.034)Jan CF 2006Population basedCross-sectional study53528 There was an inverse association betweenmetabolic syndrome and HBV infection.Chia-Chi Wang, et al. J Gastroenterol Hepatol. 2014 Aug 5. doi: 10.1111/jgh.12700. Epub ahead of print 12慢性 HBV感染与代谢综合征相关性的荟萃分析Chia-Chi Wang, et al. J Gastroenterol Hepatol. 2014 Aug 5. doi: 10.1111/jgh.12700. Epub ahead of printOR= 0.8213合并代谢综合征 (包括脂肪肝 )对 HBV肝病进展的影响肝纤维化肝硬化研究者 主要结论 来源Mena , et al. 慢性非活动性 HBV携带者，代谢综合征与纤维化发展有关J Gastroenterol Hepatol. 2014 Jan;29(1):173-8.Wong GL, et al. 慢性乙肝患者合并代谢综合征增加肝纤维化进展风险Aliment Pharmacol Ther. 2014 Apr;39(8):883-93.Wong GL, et al. 慢性乙肝患者，代谢综合征增加肝硬化风险 Gut. 2009;58(1):111-7.Huang YW, et al. 慢性乙肝合并新发糖尿病的患者，肝硬化和失代偿风险增加Clin Infect Dis. 2013. Epub ahead of print.Lin YC, et al. HBV携带者合并超声下脂肪肝：对台湾成年人的肝损伤有协同作用World J Gastroenterol. 2007;13(12):1805-10.风险14HBV携带者合并超声下脂肪肝对肝脏损伤具有协同作用Yu-Cheng Lin, et al. World J Gastroenterol 2007 ; 13(12): 1805-1810A cross-sectional retrospective analysis of health records including medical history, physical examination, abdominal sonogram, blood biochemistry and hepatic virological tests. We utilized the Students t-test, chi-square, multivariate logistic regression and synergy index to assess risks for LD.15合并 NAFLD的 CHB患者肝酶和肝组织学分期比不合并 NAFLD的 CHB升高Arezoo Estakhri, et al. Open Journal of Gastroenterology, 2012, 2:18-21 retrospectively evaluated 94 “eAg” negative CHB patients (with NAFLD: 44, without NAFLD: 50). In the NAFLD group, increase in AST, ALT, stage (P = 0.002), grade, and total score of liver biopsy were independently related to non-alcoholic fatty liver disease, while HBV-DNA viral load did not correlate with the presence of a fatty liver. 16慢性病毒性肝炎合并脂肪肝的治疗策略整体治疗的前提：脂肪肝的基础治疗最根本的治疗：抗病毒治疗重要组成部分：保肝药物改变生活方式治疗原发病和去除相关危险因素：肥胖、 2型糖尿病抗病毒药物 保肝药物一般可选用多烯磷酯酰胆碱、水飞蓟素等 1-2种，治疗半年至 1年以上。施军平 , 等 . 实用肝脏病杂志 , 2008; 11(4):278-280 17改变生活方式通过健康宣教以及心理和行为修正治疗，做到 “ 合理膳食、增加运动、节制饮酒、慎用肝毒药物以及避免接触肝毒物质 ” 。施军平 , 等 . 实用肝脏病杂志 , 2008; 11(4):278-280 18抗炎保肝类药物治疗病毒性肝炎合并脂肪肝1. 应用 IFN-类抗病毒治疗时， ALT 10ULN， TBIL50mol/L的患者；或使用过程中 ALT或 AST继续上升10ULN2. 应用 NUCs过程中少数 ALT持久波动或 ALT复升（除外耐药因素） 者（必要时寻找其他病因，相应处置）3. 使用抗病毒药物正规治疗中， ALT、 AST仍异常者 （必要时寻找其他病因，相应处置）4. ALT、 AST异常，但暂不宜应用 IFN-及 NUCs治疗的 CHB、CHC、肝硬化代偿或失代偿患者。中华医学会感染病学分会，肝脏炎症及其防治专家共识专家委员会 . 中国实用内科杂志 , 2014;34(2): 152-162针对病毒感染合并脂肪肝的患者，是否适用？19抗炎保肝药物显著改善乙肝合并脂肪肝患者的肝生化指标选择病毒性肝炎合并脂肪肝 136例， 慢性乙肝 112例 ，慢性丙肝 22例，急性乙肝 2例对照组 :一般治疗 +肝炎治疗；治疗组 :一般治疗 +肝炎治疗 +多烯磷脂酰胆碱胶囊 2片 /次 3次 /日；疗 程 :3个月姜宁华 .易善复治疗病毒性肝炎合并脂肪肝临床疗效评估 . 中国现代应用药学 .2004;21(3):235-7 20抗炎保肝药物治疗显著改善乙肝合并脂肪肝患者的影像学 选择病毒性肝炎合并脂肪肝 136例，慢性乙肝 112例，慢性丙肝 22例，急性乙肝 2例 对照组 :一般治疗 +肝炎治疗；治疗组 :一般治疗 +肝炎治疗 +多烯磷脂酰胆碱胶囊 2片 /次 3次 /日；疗 程 :3个月组间比较， p0.05姜宁华 .易善复治疗病毒性肝炎合并脂肪肝临床疗效评估 . 中国现代应用药学 .2004;21(3):235-7 21小结：慢性乙型肝炎合并脂肪肝的治疗策略 合并代谢综合征对 HBV肝病进展有影响 (如可能增加肝纤维化、肝硬化风险 )； HBV感染合并 NAFLD对肝细胞损伤有协同作用，患者肝酶和肝组织学分期比不合并 NAFLD的 CHB高； 对于慢乙肝合并脂肪肝的患者，脂肪肝的基础治疗是前提，抗病毒治疗是根本、保肝药物治疗是重要组成部分； 抗炎保肝类药物能有效改善乙肝合并脂肪肝的患者肝功能和影像学。22目 录 病毒性肝炎合并脂肪肝的流行病学 慢性乙型肝炎合并脂肪肝的危害和治疗策略 慢性丙型肝炎合并脂肪肝的危害和治疗策略23HCV在脂肪肝发生过程中的作用Anish Patel, and Stephen A. Harrison. Gastroenterology 29:10961101 25促炎因子与胰岛素抵抗发生有关A total of 28 consecutive nondiabetic patients with chronic hepatitis C were included in the study (anti-HCV). Fourteen patients with chronic hepatitis other than HCV infection served as the control group (anti-HCV). Both groups were closely matched by the main clinical variables associated with insulin resistance and the degree of liver fibrosis.ALBERT LECUBE, et al. Diabetes Care 2006; 29:10961101稳态胰岛素评价指数： HOMA-IR26代谢组学分析：丙肝患者和对照组存在差别Classification of urine samples based on P function scores obtained through the metabonomics analysis of the 1H NMR spectra model of 66 individualsM. M. G. Godoy, et al. Journal of Viral Hepatitis, 2010, 17, 854858丙肝患者的核磁共振代谢组学27FFA促进 HCV在肝细胞复制Immunohistochemical staining for HCV core antigen in the infected Huh 7.5 cells in the presence of different concentrations of FAA after 15 daysHCV infected Huh-7.5 cells were cultured with a mixture of saturated (palmitate) and unsaturated (oleate) long-chain free fatty acids (FFA). Intracytoplasmic fat accumulation in these cells was visualized by Nile red staining and electron microscopy then quantified by microfluorometry. The effect of FFA treatment on HCV replication and IFN- antiviral response was measured by flow cytometric analysis, Renilla luciferase activity, and real-time RT-PCRFeyza Gunduz, et al. Virology Journal 2012, 9:143 28游离脂肪酸降低 IFN对 HCV的治疗作用HCV infected Huh-7.5 cells were cultured with a mixture of saturated (palmitate) and unsaturated (oleate) long-chain free fatty acids (FFA). Intracytoplasmic fat accumulation in these cells was visualized by Nile red staining and electron microscopy then quantified by microfluorometry. The effect of F