病毒性肝炎合并脂肪肝的治疗策略优质推荐课件.pptx

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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,目 录病毒性肝炎合并脂肪肝的流行病学,全球和中国肝病的病因分布,Wang FS, et al. Hepatology. 2014 ;60(6):2099-108,HBV感染和脂肪肝是我国最主要的肝病病因。,全球和中国肝病的病因分布Wang FS, et al. He,14%-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,14%-71%的慢乙肝患者合并脂肪肝Raluca

2、 Pais,40-86%的慢性丙型肝炎患者合并脂肪肝,T Asselah, et al. Gut 2006;55:123130,40-86%的慢性丙型肝炎患者合并脂肪肝T Asselah,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,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Ralu,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,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肝细胞

3、癌,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？,问 题如何正确理解病毒肝与脂肪肝之间的关系？病毒性肝炎（乙,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,目 录病毒性肝炎合并脂肪肝的流行病学,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,肝脏在肥胖相关并发症发病机制中的关键

4、角色Thomas Ka,HBV 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,HBV 感染与代谢综合征：事实还是虚构？Chia-Chi W,HBV感染与代谢综合征的相互关系：临床研究汇总,Chia-Chi Wang, et al. J Gastroenterol Hepatol. 2014 Aug 5. doi: 10.1111/jgh.12700. Epub ahead of print,HBV感染与

5、代谢综合征的相互关系：临床研究汇总研究设计样本,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 print,OR= 0.82,慢性HBV感染与代谢综合征相关性的荟萃分析Chia-Chi,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,风险,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,HBV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

6、. World J Gastroenterol 2007 ; 13(12): 1805-1810,A 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 regres

7、sion and synergy index to assess risks for LD.,HBV携带者合并超声下脂肪肝对肝脏损伤具有协同作用Yu-,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,

8、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.,合并NAFLD的CHB患者肝酶和肝组织学分期比不合并NAFL,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

9、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,慢性病毒性肝炎合并脂肪肝的治疗策略整体治疗的前提：最根本的治,获得持久病毒学应答的CHC患者的HCC累积发生率C 70/59（129）In the NAFLD group, increase in AST, ALT, stage (P = 0.慢性丙型肝炎合并脂肪肝的危害和治疗策略0002 between grade 2 and grade 1

10、or grade 0).ALT降低50%有效病毒性肝炎合并脂肪肝的流行病学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；L Castera, et al.Immunohistochemical staining for HCV core antigen in the infected Huh 7.40-86%的慢性丙型肝炎患者合并脂肪肝C 70/59（129）The prevalence of metabolic syndromeWong GL, et al.Thomas Karlas, et al.J Gastroenterol Hepa

11、tol.Antiviral Research 2014;105: 92995 mg/kg body weight/weekly and ribavirin 10001200 mg/daily) for at least three months for non-responders (same virological load before and after) and for 12 months if responders or partial responders (decrease in HCV-RNA 2 log 10)Both groups were closely matched

12、by the main clinical variables associated with insulin resistance and the degree of liver fibrosis.Intracytoplasmic fat accumulation in these cells was visualized by Nile red staining and electron microscopy then quantified by microfluorometry.,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

13、肝毒物质”。,施军平, 等. 实用肝脏病杂志, 2008; 11(4):278-280,获得持久病毒学应答的CHC患者的HCC累积发生率改变生活方式,抗炎保肝类药物治疗病毒性肝炎合并脂肪肝,应用IFN-类抗病毒治疗时，ALT10ULN，TBIL50mol/L的患者；或使用过程中ALT或AST继续上升10ULN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）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）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

14、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？,抗炎保肝类药物治疗病毒性肝炎合并脂肪肝应用IFN-类抗病毒,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,抗炎保肝药物显著改善乙肝合并脂肪肝患者的

15、肝生化指标选择病毒,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,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,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

16、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。,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HB,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,目 录病毒性肝炎合并脂肪肝的流行病学,HCV在脂肪肝发生过程中的作用,Anish Patel, and Stephen A. Harrison. Gastroenterology & Hepatolo

17、gy Volume 8, Issue 5 May 2012: 305-312,HCV在脂肪肝发生过程中的作用Anish Patel, a,HCV感染患者促炎性细胞因子分泌显著增多,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

18、-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,HCV感染患者促炎性细胞因子分泌显著增多A total o,促炎因子与胰岛素抵抗发生有关,A total of 28 consecutive nondiabetic patients with chronic h

19、epatitis 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 LECU

20、BE, et al. Diabetes Care 2006; 29:10961101,稳态胰岛素评价指数：HOMA-IR,促炎因子与胰岛素抵抗发生有关A total of 28 co,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 individuals,M. M. G. Godoy, et al. Journal of Viral

21、Hepatitis, 2010, 17, 854858,丙肝患者的核磁共振代谢组学,代谢组学分析：丙肝患者和对照组存在差别Classifica,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J Gastroenterol Hepatol.ALT降低50%有效针对病毒感染合并脂肪肝的患者，是否适用？J Gastroenterol Hepatol.Clin Liver Dis 18 (2014) 165178避免使用减肥和调脂药物诱发的肝胆损伤Wong GL, et al.他汀类药物：用于CHC合并脂肪肝的治疗需要更大型、前瞻性、随机研究数据评估。8 g/天)或

22、3x 2 胶囊，安慰剂每日使用24周，有效者（ALT 下降 50）继续治疗24周，176 病人完成试验: Hep.World J Gastroenterol.metabolic syndrome and HBV infection.Feyza Gunduz, et al.慢性乙型肝炎合并脂肪肝的危害和治疗策略中国实用内科杂志, 2014;34(2): 152-162胰岛素增敏剂：改善胰岛素抵抗；2014 Aug 5.基础治疗: a-干扰素Hep.多项研究提示改变生活方式有效改善脂肪肝Arezoo Estakhri, et al.,FFA促进HCV在肝细胞复制,Immunohistochemic

23、al staining for HCV core antigen in the infected Huh 7.5 cells in the presence of different concentrations of FAA after 15 days,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 accumulati

24、on 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-PCR,Feyza Gunduz, et a

25、l. Virology Journal 2012, 9:143,选择病毒性肝炎合并脂肪肝136例，慢性乙肝112例，慢性丙肝,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

26、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-PCR,Feyza Gunduz, et al. Virology Journal 2012, 9:143,游离脂肪酸降低IFN对HC

27、V的治疗作用HCV infecte,IR降低抗病毒治疗病毒学应答率：EVR,HOMA：稳态模式评估法，Homeostasis Model Assessment，用于评估胰岛素抵抗。,J . J . BLONSKY & S. A. HARRISON. Aliment Pharmacol Ther 27, 855865,To conduct a systematic, evidence-based review of the epidemiology, pathophysiology and potential treatments of coexistent NAFLD and CHC. The

28、 terms such as hepatitis C, fatty liver, NAFLD, nonalcoholic steatohepatitis and steatosis were searched on PubMed up to January 2008. References from selected articles and pertinent abstracts were also included.,IR降低抗病毒治疗病毒学应答率：EVRHOMA：稳态模式评估,IR降低抗病毒治疗病毒学应答率：SVR,HOMA：稳态模式评估法，Homeostasis Model Asses

29、sment，用于评估胰岛素抵抗。,J . J . BLONSKY & S. A. HARRISON. Aliment Pharmacol Ther 27, 855865,To conduct a systematic, evidence-based review of the epidemiology, pathophysiology and potential treatments of coexistent NAFLD and CHC. The terms such as hepatitis C, fatty liver, NAFLD, nonalcoholic steatohepatit

30、is and steatosis were searched on PubMed up to January 2008. References from selected articles and pertinent abstracts were also included.,IR降低抗病毒治疗病毒学应答率：SVRHOMA：稳态模式评估,脂肪肝分级不同，肝细胞癌累积发生率差异显著,P = 0.0002 between grade 2 and grade 1 or grade 0).,Atsushi Tanaka, et al. World J Gastroenterol 2007 Octobe

31、r 21; 13(39): 5180-5187,获得持久病毒学应答的CHC患者的HCC累积发生率,Grade 2，Grade 1，Grade 0 指肝脂肪变分级,脂肪肝分级不同，肝细胞癌累积发生率差异显著P = 0.00,小结：与NAFLD的相互关系,胰岛素抵抗相关IR影响抗病毒疗效,脂肪肝分级与CHC患者肝细胞癌风险相关,小结：与NAFLD的相互关系NAFLDHCV胰岛素抵抗相关脂,慢性病毒性肝炎合并脂肪肝的治疗现状,改变生活方式，包括运动和减重：但在HCV合并脂肪肝人群中尚缺乏正规的临床研究数据。1抗病毒治疗。2抗炎保肝类药物：保护肝细胞、拮抗氧应激脂质过氧化、抗炎、抗凋亡、抗纤维化，还避

32、免使用减肥和调脂药物诱发的肝胆损伤。2胰岛素增敏剂：改善胰岛素抵抗；提高持久病毒学应答率？需要进一步临床研究的证明。1他汀类药物：用于CHC合并脂肪肝的治疗需要更大型、前瞻性、随机研究数据评估。1,Anish Patel, and Stephen A. Harrison. Gastroenterology 11(4):278-280,慢性病毒性肝炎合并脂肪肝的治疗现状改变生活方式，包括运动和减,多项研究提示改变生活方式有效改善脂肪肝,Valerio Nobili, et al. BMC Medicine 2011, 9:70,多项研究提示改变生活方式有效改善脂肪肝Valerio No,通过生活

33、方式干预代谢综合征对抗病毒疗效的影响,Tarantino G, et al. Gut. 2006;55:585,病毒学应答率，HCV-RNA 2 log 10,n=17,n=15,All patients were offered standard combined antiviral therapy Peg-interferon alpha 2b 1.5 mg/kg body weight/weekly and ribavirin 10001200 mg/daily) for at least three months for non-responders (same virological

34、 load before and after) and for 12 months if responders or partial responders (decrease in HCV-RNA 2 log 10),P=0.035 X2,通过生活方式干预代谢综合征对抗病毒疗效的影响Taranti,有效的抗病毒治疗显著改善基因3型丙肝患者脂肪肝情况,L Castera, et al. Gut 2004;53:420424,A total of 151 patients (37 with HCV genotype 3; 114 with HCV non-3 genotypes) were sel

35、ected to study the relationship between steatosis evolution and HCV clearance after antiviral treatment in patients with chronic hepatitis C and paired liver biopsies,Improvement was defined as a decrease of at least one grade between the two biopsies; stability was defined as identical grades betwe

36、en the two biopsies; worsening of steatosis was defined as an increase of at least one grade between the two biopsies,有效的抗病毒治疗显著改善基因3型丙肝患者脂肪肝情况L Ca,FFA促进HCV在肝细胞复制FFA促进HCV在肝细胞复制Epub ahead of print.The effect of FFA treatment on HCV replication and IFN- antiviral response was measured by flow cytometr

37、ic analysis, Renilla luciferase activity, and real-time RT-PCRL Castera, et al.Feyza Gunduz, et al.Wong GL, et al.Thomas Karlas, et al.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.抗病毒药物治疗根本脂肪肝分级不同，肝细胞癌累积发生率差异显著International Journal of Infectious Diseases 2012;16 :e43

38、6e4418 g/天)或 3x 2 胶囊，安慰剂每日使用24周，有效者（ALT 下降 50）继续治疗24周，176 病人完成试验: Hep.抗病毒治疗后与脂肪肝改善相关的独立影响因素Metabolic syndrome in HBV patientsImprovement was defined as a decrease of at least one grade between the two biopsies;World J Gastroenterol 2007 October 21; 13(39): 5180-5187合并脂肪肝对慢性病毒性肝炎患者临床预后的影响HBV感染与代谢综合征的

39、相互关系：临床研究汇总,抗病毒治疗后与脂肪肝改善相关的独立影响因素,L Castera, et al. Gut 2004;53:420424,A total of 151 patients (37 with HCV genotype 3; 114 with HCV non-3 genotypes) were selected to study the relationship between steatosis evolution and HCV clearance after antiviral treatment in patients with chronic hepatitis C a

40、nd paired liver biopsies,FFA促进HCV在肝细胞复制抗病毒治疗后与脂肪肝改善相关的,服用胰岛素增敏剂二甲双胍有效改善基因1型丙肝患者胰岛素抵抗,Peg 干扰素-+利巴韦林+二甲双胍Peg 干扰素-+利巴韦林,Jian-Wu Yu, et al. International Journal of Infectious Diseases 2012;16 :e436e441,P0.01,服用胰岛素增敏剂二甲双胍有效改善基因1型丙肝患者胰岛素抵抗,胰岛素增敏剂能否提高抗病毒治疗应答率？,Kathrin Overbeck, et al. Journal of Hepatolog

41、y 2008;49 :295298,胰岛素增敏剂能否提高抗病毒治疗应答率？Kathrin Ov,胰岛素增敏剂吡格列酮对抗病毒疗效的影响与丙肝基因型的关系,Mahmoud Khattab, et al. Liver Int. 2010 Mar;30(3):447-54,Ninety-seven previously untreated patients with CHC and IR were randomly assigned into two arms; (arm A; n = 48) were given pioglitazone 30 mg/day combined with pegin

42、terferon (Peg-IFN)-a-2b/ ribavirin (RBV) for 48 weeks, and (arm B; n = 49) were given standard of care (Peg-IFN-a-2b/RBV for 48 weeks); HOMA index and hepatitis C virus RNA (HCV RNA) levels were measured at baseline, during therapy and follow-up,胰岛素增敏剂吡格列酮对抗病毒疗效的影响与丙肝基因型的关系M,胰岛素增敏剂二甲双胍对基因1型丙肝患者抗病毒治疗

43、疗效的影响,prospective, multicentered, randomized, double-blinded, placebo-controlled trial in 19 Spanish hospitals, including 123 consecutive patients with genotype 1 chronic hepatitis C and insulin resistance. Patients were randomized to receive either metformin (arm A; n =59) or placebo (arm B; n =64)

44、 in addition to peginterferon alfa-2a (180 g/week) and ribavirin (1000-1200 mg/day). The primary end point was SVR,Manuel Romero-G omez, et al. HEPATOLOGY 2009;50:1702-1708,胰岛素增敏剂二甲双胍对基因1型丙肝患者抗病毒治疗疗效的影响,他汀对丙肝抗病毒治疗疗效的影响,Ben Verpaalen, et al. Antiviral Research 2014;105: 9299,他汀对丙肝抗病毒治疗疗效的影响Ben Verpaa

45、len,保肝药物的治疗作用,保护肝细胞,拮抗氧化应激/脂质过氧化,抗纤维化,抗凋亡,避免使用减肥和调脂药物诱发的肝胆损伤,施军平, 等. 实用肝脏病杂志, 2008; 11(4):278-280,保肝药物的治疗作用保护肝细胞拮抗氧化应激/脂质过氧化抗纤维化,抗炎保肝药物的用药原则,应按照循证医学的原则选用，以提高疗效。不宜同时应用过多特别是同类抗炎保肝药物，以免加重肝脏负担及药物间相互作用。大多数药物以口服给入。但肝衰竭时多以静脉给药为主，对肝炎突发患者常见静脉滴注后改用口服的序贯疗法。用药期间应定期观察患者的症状、体征和肝功能变化，必要时及时调整用药方案。部分药物有一定不良反应。用于肝衰竭时

46、尤应谨慎并注意鉴别，以免误判误诊。,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,抗炎保肝药物的用药原则应按照循证医学的原则选用，以提高疗效。,多烯磷脂酰胆碱联合干扰素有效提高慢性丙肝患者生化应答率(24w),Niederau C et al: Hepato Gastroenterology 1998;45:797-804,ALT降低50%有效P=0.016,治疗24周时，慢性丙肝患者的生化（ALT）应答率,ALT降低50%的病人比例,试验发现， IFN+PPC组比 IFN+安慰剂组可实现更好的ALT治疗反应率。在 24

47、周时，ALT降低50%的病人比例IFN+PPC组显著多于IFN+安慰剂组。表明，多烯磷脂酰胆碱胶囊可以改善病毒性肝炎患者的肝功能水平，有效治疗病毒性肝炎。,基础治疗: a-干扰素Hep.B: 5 mio I.U. s.c. 3x 每周，24周，Hep.C: 3 mio I.U. s.c. 3x 每周，24周。试验药物:3 x 2 胶囊， PPC 每日使用 (1.8 g/天)或 3x 2 胶囊，安慰剂每日使用24周，有效者（ALT 下降 50）继续治疗24周，176 病人完成试验: Hep.B. 22/25（47）， Hep.C 70/59（129）,多烯磷脂酰胆碱联合干扰素有效提高慢性丙肝患者

48、生化应答率(2,多烯磷脂酰胆碱联合干扰素48周时慢性丙肝患者ALT复常率,Niederau C et al: Hepato Gastroenterology 1998;45:797-804,P=0.06,治疗24周时ALT降低50的病人，停用IFN，继续使用PPC（每日3次，每次2粒）或安慰剂治疗，第48周时的ALT复常率,ALT正常的病人比例,基础治疗: a-干扰素Hep.B: 5 mio I.U. s.c. 3x 每周，24周，Hep.C: 3 mio I.U. s.c. 3x 每周，24周。试验药物:3 x 2 胶囊， PPC 每日使用 (1.8 g/天)或 3x 2 胶囊，安慰剂每日使

49、用24周，有效者（ALT 下降 50）继续治疗24周，176 病人完成试验: Hep.B. 22/25（47）， Hep.C 70/59（129）,多烯磷脂酰胆碱联合干扰素48周时慢性丙肝患者ALT复常率N,基础治疗: a-干扰素Hep.0002 between grade 2 and grade 1 or grade 0).小结：丙肝合并脂肪肝的危害和治疗策略通过生活方式干预代谢综合征对抗病毒疗效的影响实用肝脏病杂志, 2008; 11(4):278-280Gut 2004;53:4204240002 between grade 2 and grade 1 or grade 0).J Gas

50、troenterol Hepatol.合并脂肪肝对慢性病毒性肝炎患者临床预后的影响治疗原发病和去除相关危险因素：肥胖、2型糖尿病游离脂肪酸降低IFN对HCV的治疗作用2004;21(3):235-7易善复治疗病毒性肝炎合并脂肪肝临床疗效评估.International Journal of Infectious Diseases 2012;16 :e436e441Cross-section针对病毒感染合并脂肪肝的患者，是否适用？慢性病毒性肝炎合并脂肪肝的治疗现状如何正确理解病毒肝与脂肪肝之间的关系？中国实用内科杂志, 2014; 34(2):152-162J Gastroenterol Hep