,*,xxxx,教授,中国医大一院老年消化内分泌科主任 教授、博士生导师,中国医师协会脂肪肝专家委员会 副主任委员,中华消化学会老年协作组 副组长,中华消化学会肝胆协作组 组员,中华医学会辽宁省消化分会 副主任委员,辽宁省中西医结合肝病学会 副主任委员,辽宁省医学会肝病分会 常委,辽宁省免疫学会老年免疫分会 主任委员,xxxx 教授中国医师协会脂肪肝专家委员会,The effect of glucocorticoid in,Alcoholic hepatitis,Wang Bing Yuan(xxx),Department of Geriatric Gastroenterology,The First Hospital of China Medical University,Shenyang,CHINA,（,中国医科大学附属第一医院老年消化科,沈阳，中国,）,The effect of glucocorticoid i,Heavy drinkers are at risk for a spectrum of histologic alcohol-related liver injury:,Steatosis,Alcoholic steatohepatitis(ASH),alcohol-related fibrosis,and,cirrhosis.,Alcoholic hepatitis(AH),the clinical entity associated with severe ASH,has high short-term mortality.,Introduction,Heavy drinkers are at risk for,Pathogenesis of AH,Pathogenesis of AH,Bernd Schnabl.Hepatology 2016.,Bernd Schnabl.Hepatology 2016,Clinical and Laboratory Features of AH,Clinical and Laboratory Featur,Yeluru,et al.Alcohol Clin Exp Res,2016:pp 246255,Common Clinical and Laboratory Features of AH,Intrahepatic cholestasis,IHC,Yeluru,et al.Alcohol Clin Ex,Histological characteristics of AH,Histological characteristics o,Yeluru,et al.Alcohol Clin Exp Res,2016:pp 246255,An integrated approach to treating alcoholic hepatitis.,antioxidant,Metadoxine,baclofen,The management of liver disease complications and supportive care,1.,5,7.,10.,4.,3.,2.,9.,6.,8.,Yeluru,et al.Alcohol Clin Ex,抗炎,保肝药物的分类,.,王宇明,.,抗炎保肝药物的作用机制及地位,.,中华肝脏病杂志,2011,19(1):76-77.,抗炎保肝药物的分类.王宇明.抗炎保肝药物的作用机制及地位.中,ROS,启动,Caspase,（,8,）,LOX,前列腺素,白三烯,血栓素,NF-kB,TNF,/Fas,SOD,异甘草酸镁,易善复,谷胱甘肽,NADPH II,氧化酶,ONOO-,iNOS,溶血磷脂胆碱,LPC,脂质神经酰胺,3,种抗炎保肝药物的作用靶点,启动 Caspase（8）LOX前列腺素NF-kBTNF/,Yeluru,et al.Alcohol Clin Exp Res,2016:pp 246255,An integrated approach to treating alcoholic hepatitis.,Europe:,methylprednisolone 40mg,iv,qd,28d,our experience:,methylprednisolone,120mg,iv,3d and 7d.,TBiL:decreased by 10%on days 3 or decreased by 30%on days 7,continue to DF down to 32 or less,gradually decrease the dosage or stop.,Lille score 0.45,10.,Yeluru,et al.Alcohol Clin Ex,The effect of glucocorticoid,The effect of glucocorticoid,Prognostic scoring systems of alcoholic hepatitis,Prognostic scoring systems of,Please remember,：,Please remem,From 1971 through 2014,13 randomized trials and 4 meta-analyses investigated the,effects of corticosteroids in patients with AH.,Although these studies produced many,results,controversy persisted over the use of corticosteroid therapy in these patients.,Advocates cite reductions in short-to medium-term mortality,whereas detractors raise,concerns about risks of sepsis and gastrointestinal hemorrhage.,From 1971 through 2014,13 ran,The largest placebo-controlled study of the effects of corticosteroids,in 90 patients with,AH,found prednisolone to provide no benefit compared with placebo.,This study was,hampered by its inclusion of patients with moderate and severe AH or end-stage,alcoholic liver disease.,In studies that required histological confirmation of AH,prednisolone was associated with a short-term decrease in mortality,but there was no,reduction in mortality over 6 months,N.Engl.J.Med.,184,，,311,The largest placebo-controlled,Systematic reviews of these clinical trials,generated conflicting results.,A Cochrane meta-analysis reported a trend toward,but not,a not statistically significant,increase in survival.,However a re-analysis of the 3 largest,studies indicated that corticosteroids significantly increased survival of patients with AH.In this study,15%of patients with DF values of 32 or more given prednisolone died within 28 days,compared to 35%of patients given placebo.,Gut.2011;60:255-260.,Systematic reviews of these cl,In an attempt to resolve the controversy over the use of steroids or pentoxifylline,a,double blind,factorial 2 x 2,multicenter trial was conducted in the United Kingdom,between 2011 and 2014 in patients with a diagnosis of AH(the,STOPAH,trial).,This,study reported a borderline reduction in mortality at 28 days for patients given,prednisolone 40 mg daily for 28 days compared with control patients.,N Engl J Med.2015;372:1619-28.,In an attempt to resolve the c,However,survival curves converged after 28 days such that prednisolone therapy provided no,benefit to patients after 90 days or 1 year.,Data from this trial and previous studies were,incorporated into a network meta-analysis,which confirmed that corticosteroids do not,benefit patients beyond the first month of treatment.,Gastroenterology.2015;149:958,However,survival curves conve,Two factors potentially limit the efficacy of corticosteroid use:increased susceptibility to,infection and recidivism.In the STOPAH trial,incident infections classified as serious,adverse events were more common among subjects given prednisolone than controls.,Infections of the respiratory tract were particularly more common.However,in the metaanalysis,of Singh et al,infection was not any more common among patients treated with,vs without corticosteroids.,This apparent discrepancy could have been caused by,differ