停用核苷和核苷酸类药物抗HBV后诱发慢加急性肝衰竭的临床特征

胡高飞; 李小鹏; 吴振平; 梅清; 李丹; 张文苑; 余婷婷; 程娜; 张伦理

doi:10.3969/j.issn.1001-5256.2017.07.023

停用核苷和核苷酸类药物抗HBV后诱发慢加急性肝衰竭的临床特征

DOI: 10.3969/j.issn.1001-5256.2017.07.023

南昌大学第一附属医院感染病科江西省肝脏再生医学重点实验室

基金项目:

江西省科技支撑计划社发项目(20151BBG70221)；

详细信息

中图分类号: R512.62;R575.3
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出版历程
- 收稿日期: 2017-01-16
- 出版日期: 2017-07-20

Clinical features of acute-on-chronic liver failure induced by withdrawal of nucleos (t) ide analogues

Department of Infectious Diseases, The First Affiliated Hospital of Nanchang University & Jiangxi Key Laboratory of Liver Regenerative Medicine

Research funding:

摘要

摘要:
目的探讨患者停用核苷和核苷酸类药物（NAs）抗HBV后诱发慢加急性肝衰竭（ACLF）的临床特征。方法回顾性分析2014年6月-2016年10月南昌大学第一附属医院收治的确诊为ACLF的患者865例,其中因停药诱发ACLF的患者137例（停药组）,非停用NAs诱发ACLF的患者728例（非停药组）,详细记录患者抗病毒药物种类、规范抗病毒持续时间、停药方式、停药至发生肝衰竭时间、停药后监测情况、肝脏基础疾病、进展为ACLF后30 d病死率等。计量资料组间比较采用t检验;计数资料组间比较采用χ2检验。结果非停药组728例患者中治愈或好转、死亡或无效分别为389例和339例。137例停药组患者中慢性病毒性肝炎基础69例,其中治愈或好转、死亡或无效分别为40例和29例;肝硬化基础68例,其中治愈或好转、死亡或无效分别为16例和52例,差异有统计学意（χ2=16.81,P<0.001）。137例停药患者中停药前服用拉米夫定占24.09%（33/137）,阿德福韦酯占34.31%（47/137）,拉米夫定联合阿德福韦酯占11.68%（16/137）,...
- 肝功能衰竭 /
- 肝炎病毒,乙型 /
- 核苷类 /
- 核苷酸类
Abstract:
Objective To investigate the clinical features of patients with hepatitis B virus-related acute-on-chronic liver failure (ACLF) induced by the withdrawal of nucleos (t) ide analogues (NAs) .Methods A retrospective analysis was performed for the clinical data of 865 patients who were admitted to The First Affiliated Hospital of Nanchang University from June 2014 to October 2016 and diagnosed with ACLF.Among these patients, 137 experienced ACLF induced by drug withdrawal (withdrawal group) and 728 experienced ACLF not induced by drug withdrawal (non-withdrawal group) .The type of antiviral drugs, duration of standard antiviral therapy, withdrawal way, time from withdrawal to the development of liver failure, monitoring after withdrawal, underlying liver diseases, and 30-day mortality after progression to ACLF were recorded in detail.The t-test was used for comparison of continuous data between groups, and the chi-square test was used for comparison of categorical data between groups.Results Of all the 728 patients in the non-withdrawal group, 389 were cured or improved and 339 died or had no response.Of all the 137 patients in the withdrawal group, 69 had chronic viral hepatitis, among whom 40 were cured or improved and 29 died or had no response;68 had liver cirrhosis, among whom 16 were cured or improved and 52 died or had no response;there was a significant difference (χ2=16.81, P<0.001) 6="" 16="" 25="" 32="" 33="" 37="" 47="" 79="" 137="" .of="" all="" the="" patients="" in="" withdrawal="" before="" used="" adefovir="" lamivudine="" combined="" with="" and="" entecavir.of="" when="" they="" developed="" had="" a="" duration="" of="" drug="" 6-12="">12 months.Conclusion Improper withdrawal of NAs can easily induce ACLF.The changes in virologic parameters, liver function parameters, and liver imaging findings should be closely monitored for patients with hepatitis B within 6 months after withdrawal.Underlying liver diseases determine the development and prognosis of ACLF after withdrawal, and long-term standard antiviral therapy is of great importance in patients with liver cirrhosis.
- liver failure /
- hepatitis B virus /
- nucleosides /
- nucleotides

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参考文献(17)

[1]Chinese Society of Hepatology and Chinese Society of Infectious Diseases, Chinese Medical Association.The guideline of prevention and treatment for chronic hepatitis B:a 2015 update[J].J Clin Hepatol, 2015, 31 (12) :1941-1960. (in Chinese) 中华医学会肝病学分会, 中华医学会感染病学分会.慢性乙型肝炎防治指南 (2015年更新版) [J].临床肝胆病杂志, 2015, 31 (12) :1941-1960.

[2]ZHAN DA, LIU H, CHEN XJ, et al.The clinical efficacy of telbivudine and adefovir ester combination therapy of hepatitis B patients with high viral loads[J].Int J Virol, 2016, 23 (1) :17-19. (in Chinese) 詹东昂, 刘华, 陈秀记, 等.替比夫定联用阿德福韦酯在高病毒载量乙肝患者中的应用效果[J].国际病毒学杂志, 2016, 23 (1) :17-19.

[3]ZHANG Y, YU YS, TANG ZH, et al.Clinical study of entecavir combined with kushenin improving the Th1/Th2 imbalance in patients with HBe Ag-positive chronic hepatitis B[J].Chin J Clin Pharmacol Ther, 2016, 21 (10) :1168-1172. (in Chinese) 张毅, 余永胜, 汤正好, 等.恩替卡韦联合苦参素改善HBe Ag阳性慢性乙型肝炎患者Th1/Th2失平衡临床研究[J].中国临床药理学与治疗学, 2016, 21 (10) :1168-1172.

[4] Liver Failure and Artificial Liver Group, Chinese Society of Infectious Diseases, CMA;Severe Liver Disease and Artificial Liver Group, Chinese Society of Hepatology, CMA.Guideline for diagnosis and treatment of liver failure (2012 version) [J].Chin J Clin Infect Dis, 2012, 5 (6) :321-327. (in Chinese) 中华医学会感染病学分会肝衰竭与人工肝治疗组, 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) [J].中华临床感染病杂志, 2012, 5 (6) :321-327.

[5]FENG H, HE GP.The study of the compliance of patients with chronic hepatitis B and influence factors[J].Chin J Nurs, 2005, 40 (12) :891-894. (in Chinese) 冯辉, 何国平.慢性乙型病毒性肝炎患者治疗依从性及其影响因素分析[J].中华护理杂志, 2005, 40 (12) :891-894.

[6]SHOUVAL D, LAI CL, CHANG TT, et al.Relapse of hepatitis B in HBe Ag-negative chronic hepatitis B patients who discontinued successful entecavir treatment:the case for continuous antiviral therapy[J].J Hepatol, 2008, 50 (2) :289-295.

[7]HADZIYANNIS SJ, TASSOPOULOS NC, HEATHCOTE EJ, et al.Long-term therapy with adefovirdipivoxil for HBe Ag-negative chronic hepatitis B[J].N Eng J Med, 2005, 352 (26) :2673-2681.

[8]LIU XY, CHEN J, XIAO L, et al.Clinical features of HBV-associated acute-on-chronic liver failure induced by discontinuation of nucleoside analogues[J].J Clin Hepatol, 2016, 32 (9) :1766-1769. (in Chinese) 刘晓燕, 陈婧, 肖珑, 等.停用核苷和核苷酸类药物诱发HBV相关慢加急性肝衰竭患者的临床特点分析[J].临床肝胆病杂志, 2016, 32 (9) :1766-1769.

[9] LI XP, LEI W, ZHANG LL, et al.The clinical significance of stop using nucleotide (acid) antiviral drugs ininduced factors of severe hepatitis[C].The 16th national congress of viral hepatitis and liver disease in China, 2013. (in Chinese) 李小鹏, 雷湾, 张伦理, 等.停用核苷 (酸) 类抗病毒药物在重型肝炎诱发因素中的临床意义[C].中华医学会第十六次全国病毒性肝炎及肝病学术会议论文汇编, 2013.

[10]PHILLIPS S, CHOKSHI S, RIVA A, et al.CD8 (+) T cell control of hepatitis B virus replication:direct comparison between cytolytic and noncytolyticfunctions[J].J Immunol, 2010, 184 (1) :287-295.

[11]BONI C, LACCABUE D, LAMPERTICO P, et al.Restored function of HBV-specific T cells afterlong-term effective therapy with nucleos (t) ide analogues[J].Gastroenterology, 2012, 143 (4) :963-973, e969.

[12]LIU BX, ZHANG LL, ZHANG WF.Changes of hepatitis B core antigen-specific cytotoxic T lymphocytes in chronic hepatitis B patients during antiviral treatment and relapse after withdrawal of treatment[J].Chin J Infect Dis, 2016, 34 (8) :480-484. (in Chinese) 刘碧霞, 张伦理, 张文峰.慢性乙型肝炎患者抗病毒治疗与停药复发后体内乙型肝炎核心抗原特异性T淋巴细胞变化[J].中华传染病杂志, 2016, 34 (8) :480-484.

[13]SEEGER C, MASON WS.Molecular biology of hepatitis B virus infection[J].Virology, 2015, 479-480:672-686.

[14]LIU BX, ZHANG LL, LI XP, et al.Curative effect of chronic hepatitis B second treatment with entecavir when non-standarded stopantiviral therapy[J].Guangdong Med J, 2015, 36 (8) :1263-1265. (in Chinese) 刘碧霞, 张伦理, 李小鹏, 等.慢性乙型肝炎不规范停用恩替卡韦复发后再次恩替卡韦治疗的效果[J].广东医学, 2015, 36 (8) :1263-1265.

[15]TSOCHATZIS EA, BOSCH J, BURRROUGHS AK.Liver cirrhosis[J].Lancet, 2014, 383 (9930) :1749-1761.

[16]WU GC, ZHOU WP, ZHAO YR, et al.A study on the long-term outcome of hepatitis B e antigen-negative chronic hepatitis B compared with that of hepatitis B e antigen-positive chronic hepatitis B[J].Chin J Infect Dis, 2007, 25 (3) :166-168. (in Chinese) 巫贵成, 周卫平, 赵有蓉, 等.乙型肝炎e抗原阴性和阳性慢性乙型肝炎患者临床转归的回顾性分析[J].中华传染病杂志, 2007, 25 (3) :166-168.

[17]KANG W, PARK JY.When to stop nucleos (t) ide analogues treatment for chronic hepatitis B?Durability of antiviral response[J].World J Gastroenterol, 2014, 20 (23) :7207-7212.

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