应用糖皮质激素治疗核苷(酸)类似物撤药性肝炎患者临床疗效评价
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摘要
目的探讨应用糖皮质激素治疗因不当停止核苷(酸)类似物(NAs)引起的撤药性肝炎(WH)患者对阻止病情进展的作用。方法 2017年12月～2018年12月我科收治的因停用NAs导致的WH且符合肝衰竭前期患者23例,其中11例接受恩替卡韦抗病毒和内科综合治疗,另12例在前述治疗的基础上接受氢化可的松琥珀酸钠静脉滴注治疗,观察8周。结果在观察8周结束时,皮质激素治疗组因病情进展至肝衰竭死亡1例,常规治疗组死亡3例;皮质激素治疗组病情控制时间为(22.4±9.4) d,显著短于常规治疗组[(36.7±13.1) d,P<0.05];治疗前,两组血清TBIL、ALB、PTA和终末期肝病模型评分(MELD)水平无显著性差异(P>0.05),但在治疗8周时,皮质激素治疗组分别为(20.8±11.6)μmol/L、(38.3±5.2)g/L、(68.9±11.2)%和(4.8±2.2),与常规治疗组的【(56.7±81.4)μmol/L、(34.7±23.1)g/L、(55.5±34.8)%和(10.9±2.6),P<0.05】比,差异显著。结论应用糖皮质激素治疗处于肝衰竭前期的WH患者能快速阻断病情进展,大多预后良好,且无严重的并发症发生,值得进一步研究。
Objective The aim of this study was to investigate the clinical efficacy of glucosteroid on blocking disease progress in patients with nucleos(t)ide analogue(NAs) withdrawal hepatitis(WH). Methods 23 patients with NAsWH,who were diagnosed as in the tendency to hepatic failure owing to inappropriate NAs withdrawal,were recruited in this study,and 11 received conventional supporting therapy at base of enticavir antiviral treatment,and other 12 received hydrocortisone sodium pine succinate at dose of 100 mg daily and tapered as liver function improved. Results At the end of eight week observation,one patient in steroid-treated groupd,and three patients in the conventional treatment died because of progress to liver failure;the disease control time in the former was(22.4±9.4) d,significantly shorter than [(36.7±13.1) d,P<0.05] in the latter;at presentation,serum bilirubin,albumin,prothrombin time activities and model of end-stage liver disease scores in the two groups were not significantly different(P >0.05),while at the end of eight-week observation,they were(20.8 ±11.6) μmol/L,(38.3±5.2) g/L,(68.9±11.2)% and(4.8±2.2) in the former,significantly different as compared to [(56.7±81.4)μmol/L,(34.7 ±23.1)g/L,(55.5 ±34.8)% and(10.9 ±2.6),P <0.05] in the latter. Conclusion The application of steroid for blocking disease progress to liver failure in patients with NAsWH might be efficacious,which needs further investigation.
Objective The aim of this study was to investigate the clinical efficacy of glucosteroid on blocking disease progress in patients with nucleos(t)ide analogue(NAs) withdrawal hepatitis(WH). Methods 23 patients with NAsWH,who were diagnosed as in the tendency to hepatic failure owing to inappropriate NAs withdrawal,were recruited in this study,and 11 received conventional supporting therapy at base of enticavir antiviral treatment,and other 12 received hydrocortisone sodium pine succinate at dose of 100 mg daily and tapered as liver function improved. Results At the end of eight week observation,one patient in steroid-treated groupd,and three patients in the conventional treatment died because of progress to liver failure;the disease control time in the former was(22.4±9.4) d,significantly shorter than [(36.7±13.1) d,P<0.05] in the latter;at presentation,serum bilirubin,albumin,prothrombin time activities and model of end-stage liver disease scores in the two groups were not significantly different(P >0.05),while at the end of eight-week observation,they were(20.8 ±11.6) μmol/L,(38.3±5.2) g/L,(68.9±11.2)% and(4.8±2.2) in the former,significantly different as compared to [(56.7±81.4)μmol/L,(34.7 ±23.1)g/L,(55.5 ±34.8)% and(10.9 ±2.6),P <0.05] in the latter. Conclusion The application of steroid for blocking disease progress to liver failure in patients with NAsWH might be efficacious,which needs further investigation.
引文
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[18]Cui YL,Yan F,Wang YB,et al.Nucleoside analogue can improve the long-term prognosis of patients with hepatitis Bvirus infection associated acute on chronic liver failure.Dig Dis Sci,2010,55:2373-2380.
[19]Duseja A,Chawla YK,Dhiman RK.Non-hepatic insules are common acute precipitants in patients with acute on chronic liver failure(ACLF).Dig Dis Sci,2010,55:3188-3192.
[20]Kandiah PA,Olson JC,Subramanian RM.Emerging strategies for the treatment of patients with acute hepatic failure.Curr Opin Crit Care,2016,22(2):142-151.
[2]Heathcote EJ,Marcellin P,Buti M,et al.Three-year efficacy and safety of tenofovir disoproxil fumarate treatment for chronic hepatitis B.Gastroenterology,2011,140:132-143.
[3]Thompson AJ,Nguyen T,Iser D,et al.Serum hepatitis B surface antigen and hepatitis B e antigen titers:disease phase influences correlation with viral load and intrahepatic hepatitis B virus markers.Hepatology,2010,51:1933-1944.
[4]中华医学会感染病学分会,中华医学会肝病学分会.慢性乙型肝炎防治指南(2015年版).实用肝脏病杂志,2016,19(3):Ⅴ-ⅩⅥ.
[5]中华医学会感染病学分会肝衰竭与人工肝学组.肝衰竭诊治指南(2012年版).中华肝脏病杂志,2013,21(3):210-216.
[6]Locarnini S,Hatzakis A,Heathcote J,et al.Management of antiviral resistance in patients with chronic hepatitis B.Antiviral Ther,2004,9:679-693.
[7]Lee KM,Cho SW,Kim SW,et al.Effect of virological response on post-treatment durability of lamivudine-induced HBe Ag serocon-version.J Viral Hepat,2002,9:208-212.
[8]叶一农,高志良.乙型肝炎肝衰竭发生机制中的三重打击.中华肝脏病杂志,2009,17:638-640.
[9]Zheng YB,Huang ZL,Wu ZB,et al.Dynamic changes of clinical features that predict the prognosis of acut-on-chronic hepatitis B live failure:a retrospective cohort study.Int J Med Sci,2013,10:1658-1644.
[10]Sarin SK,Kumer A,AlMELDa JA,et al.Acute-on-chronic liver failure:consensus recommendations of the Asian Pacific Association for the study of the liver(APASL).Hepatol Int,2009,3:269-281.
[11]Lee WM,Stravitz RT,Larsin AM,et al.Introdution to the revised American Association for the Study of Liver Diseases Position Paper on acute liver failure 2011.Hepatology,2012,55:965-967.
[12]Baschant U,Tuckermann J.The role of the glucocorticoid receptor in inflammation and immunity.J Steroid Biochem,2010,120(2-3):69-75.
[13]Dejager L,Vandevyver S,Petta I,et al.Dominance of the strongest:inflammatory cytokines versus glucocorticoids.Cytok Growth Factor Rev,2014,25(1):21-33.
[14]Fede G,Spadaro L,Tomaselli T,et al.Adrenocortical dysfunction in liver disease:a systematic review.Hepatology,2012,55:1282-1291.
[15]Fujiwara K,Yokosuka O,Kojima H,et al.Importance of adequate immunosuppressive therapy for the recovery of patients with“life-threatening”severe exacerhation of chronic hepatitis B.World J Gastroenterol,2005,11:1109-1114.
[16]汤伟良,谢青.乙型肝炎相关性肝衰竭抗病毒治疗研究进展.中华肝脏病杂志,2012,20:408-410.
[17]Sun LJ,Yu JW,Zhao YH,et al.Influential of prognosis in lamivudine treatment for patients with acute-on-chronic hepatitis B liver failure.J Gastroenterol Hepatol,2010,25:583-590.
[18]Cui YL,Yan F,Wang YB,et al.Nucleoside analogue can improve the long-term prognosis of patients with hepatitis Bvirus infection associated acute on chronic liver failure.Dig Dis Sci,2010,55:2373-2380.
[19]Duseja A,Chawla YK,Dhiman RK.Non-hepatic insules are common acute precipitants in patients with acute on chronic liver failure(ACLF).Dig Dis Sci,2010,55:3188-3192.
[20]Kandiah PA,Olson JC,Subramanian RM.Emerging strategies for the treatment of patients with acute hepatic failure.Curr Opin Crit Care,2016,22(2):142-151.