恩替卡韦治疗慢加亚急性乙型肝炎肝衰竭临床观察

doi:10.3969/.j.issn.1672-5069.2015.06.010

摘要/Abstract

摘要： 目的探讨恩替卡韦治疗慢加亚急性乙型肝炎肝衰竭（HBV-ACLF）患者的疗效。方法选择 2003年~2012年在本院住院并应用恩替卡韦抗乙型肝炎病毒治疗的HBV-ACLF患者37例作为治疗组,同时选择在本院住院未应用任何抗乙型肝炎病毒药物的HBV-ACLF患者37例作为对照组。采用回顾性研究方法比较两组患者临床体征、血生化指标、终末期肝病模型（MELD）评分、累积生存率和2 年内复发率情况。结果在入院时、治疗后4w、8w、12w时,治疗组患者外周血谷丙转氨酶（ALT）、谷草转氨酶（AST）、血总胆红素（TBIL）、血肌酐（Cr）,凝血酶原活动度（PTA）和MELD评分与对照组相比,差异均无统计学意义（P>0.05）;两组腹水、消化道出血、肝性脑病和肝肾综合征发生率比较,除在治疗4w末时,治疗组生存者腹水发病率为41.4%,低于对照组生存者的66.7%（P<0.05）,余无统计学差异（P>0.05）;在治疗8w、12w和24w时,37例抗病毒患者生存率分别为75.7%、75.7%和70.3%,均明显高于对照组的67.6%、56.8%和54.1%（P<0.05）;26例抗病毒的生存患者在2年内病情无复发,而20例未抗病毒的生存患者复发率为65.0%（P<0.001）。结论给予HBV-ACLF患者恩替卡韦抗病毒治疗,可提高生存率,减少病情复发。

关键词: 乙型肝炎, 慢加亚急性肝衰竭, 恩替卡韦, 治疗, 生存率

Abstract: ObjectiveTo investigate the efficacy of entecavir in treatment of patients with HBV-associated acute-on-chronic liver failure（HBV-ACLF）. Methods 74 patients with HBV-ACLF were enrolled in Third People’s Hospital,Nantong,from 2003 to 2012. Among them,37 patients were given entecavir while receiving liver-protecting treatment,and the other 37 cases were given only basic protecting treatment without any antiviral medication as control group. The clinical characteristic at administration,the results of liver function such as alanine transaminase （ALT）,aspartate transaminase（AST）,albumin （ALB）,creatine（Cr）,prothrombin time （PT） , the score of model for end-stage liver disease （MELD）,cumulative survival rates and recurrence rates within 24 months were compared between the two groups by means of t-test and Chi-Square test. ResultsThe serum levels of ALT,AST,ALB,Cr,plasma prothrombin activity（PTA） and MELD scores between the two groups had no statistical differences after 4-week,8-week and 12 week treatment;The morbidity of ascites,gastrointestinal bleeding,encephalopathy,and hepatorenal syndrome between the two groups had no statistical differences except the morbidity of ascites in the survivors of the entecavir group was 41.4%,lowwer than 66.7%（P<0.05） in the control group at the end of the fourth week;The survival rates in 37 patients receiving antiviral therapy at 8w,12w and 24w,were 75.7%,75.7% and 70.3%,much higher than 67.6%,56.8% and 54.1%（P<0.05）in the control;At the end of 2-year observation, there was no recurrence in 26 survivals with entecavir treatment, while the recurrence rate was 65.0%（P<0.001） in 20 patients without antiviral therapy in the control. ConclusionEnticavir treatment may improve the survival of patients with HBV-ACLF with less disease recurrence.

Key words: Hepatitis B, Acute-on-chronic liver failure, Entecavir, Therapy, Survival rate

任金才，宋建华，宋铮，邵建国，朱勇根. 恩替卡韦治疗慢加亚急性乙型肝炎肝衰竭临床观察[J]. 实用肝脏病杂志, 2015, 18(6): 603-606.

Ren Jincai， Song Jianhua， Song Zheng， et al.. Clinical observation of enticavir in treatment of patients with HBV-associated acute-on-chronic liver failure[J]. JOURNAL OF PRACTICAL HEPATOLOGY, 2015, 18(6): 603-606.

参考文献

[1] 中华医学会感染病学分会肝衰竭与人工肝学组和中华医学会肝病学分会重型肝病与人工肝学组. 肝衰竭诊治指南（2012年版）. 实用肝脏病杂志,2013,16（3）:210-216.
[2] Organization Committee of 13th Asia-Pacific Congress of Clinical Microbiology Infection. 13th Asia-Pacific Congress of Clinical Microbiology and Infection Consensus Guidelines for diagnosis and treatment of liver failure. Hepatobiliary Pancreatic Dis Int,2013,12（4）：346-354.
[3] Tenney DJ,Rose RE,Baldick CJ,et al. Long-term monitoring shows hepatitis B virus resistance to entecavir in nucleoside-naive patients is rare through 5 years of therapy. Hepatology,2009,49（5）：1503-1514.
[4] 舒欣,徐启桓,陈旎,等. 恩替卡韦在乙型肝炎慢加急性肝功能衰竭中的应用. 中华传染病杂志,2009,27（5）:281-286.
[5] 周秀云. 恩替卡韦治疗慢性乙型重型肝炎近期疗效观察. 实用肝脏病杂志,2007,10（5）:330-331.
[6] Wong VWS,Wong GLH,Chim AML,et al. Entecavir treatment in patients with severe acute exacerbation of chronic hepatitis B. J Hepatol,201,54（2）：236-242.
[7] 叶一农,高至良. 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（8）：638-640.
[8] 田辉,孙颖,滕光菊,等. 慢加急性乙型肝炎肝衰竭患者肝组织IFN-γ、TNF-α和IL-10的表达. 实用肝脏病杂志,2011,14（2）：116-118.
[9] Villeneuve JP,Condreay LD,Willems B,et al. Lamivudine treatment for decompensated cirrhosis resulting from chronic hepatitis B. Hepatology,2000,31（1）：207-210.
[10] Tillmann HL,Zachou K,Dalekos GN. Management of severe acute to fulminant hepatitis B:to treat or not to treat or when to treat Liver Int,2012,32（4）:544-553.
[11] 宋闽宁,闵峰,黄文琪. 拉米夫定治疗肝衰竭8年随访. 实用肝脏病杂志,2009,12（6）：427-429.
[12] 张骏飞,刘波,杨家宏,等. 拉米夫定治疗乙型肝炎肝衰竭的临床观察. 实用肝脏病杂志, 2010,13（6）:411-413.
[13] 黎志良,李金庚. 拉米夫定治疗慢加急性乙型肝炎肝衰竭28例临床分析. 实用肝脏病杂志,2011,14（5）:364-365.
[14] Chen TY,He YL,Liu XJ,et al. Nucleoside analogues improve the short-term and long-term prognosis of patients with hepatitis B virus-related acute-on-chronic liver failure. Clin Exp Med,2012,12（3）：159-164.
[15] Lin BL,Pan CQ,Xie DY,et al. Entecavir improves the outcome of acute-on-chronic liver failure due to the acute exacerbation of chronic hepatitis B. Hepatol Int,2013,7（2）：460-467.
[16] Ma K,Guo W,Han MF,et al. Entecavir treatment prevents disease progression in hepatitis B virus-related acute-on-chronic liver failure:establishment of a novel logistical regression model. Hepatol Int,2012,6（4）: 735-743.
[17] Liu CH,Ye J,Zhang MJ,et al. Entecavir and lamivudine therapy for severe acute chronic hepatitis B. Exp Therapeut Med,2013,5（2）: 545-548.
[18] Cui YL,Yan F,Wang YB,et al. Nucleoside analogue can improve the long-term prognosis of patients with hepatitis B virus infection-associated acute on chronic liver failure. Dig Dis Sci,2010,55（8）:2373-2380.
[19] Chen J,Han JH,Liu C,et al. Short-term entecavir therapy of chronic severe hepatitis B. Hepatobiliary Pancreat Dis Int,2009,8（3）:261-266.
[20] Yan Y,Mai L,Zheng YB,et al. What MELD score mandates use of entecavir for ACLF-HBV HBeAg-negative patients. World J Gastroenterol,2012,18（33）：4604-4609.