切换至 "中华医学电子期刊资源库"

中华实验和临床感染病杂志(电子版) ›› 2016, Vol. 10 ›› Issue (05) : 527 -533. doi: 10.3877/cma.j.issn.1674-1358.2016.05.004

所属专题: 指南共识

指南

慢性乙型肝炎核苷(酸)类似物经治患者抗病毒治疗专家共识:2016年更新
慢性乙型肝炎核苷(酸)类似物经治患者抗病毒治疗专家委员会   
  • 收稿日期:2016-08-22 出版日期:2016-10-15
  • 基金资助:
    北京市医院管理局扬帆计划项目(肝炎专业)(No. ZYLX201402); 登峰计划项目(肝病专业)(No. DFL20151701)

Expert consensus on antiviral therapy in nucleos(t)ide analogues experienced patients with chronic hepatitis B: 2016 update

Committee of experts on antiviral therapy in nucleos(t)ide analogues experienced patients with chronic hepatitis B   

  • Received:2016-08-22 Published:2016-10-15
引用本文:

慢性乙型肝炎核苷(酸)类似物经治患者抗病毒治疗专家委员会. 慢性乙型肝炎核苷(酸)类似物经治患者抗病毒治疗专家共识:2016年更新[J]. 中华实验和临床感染病杂志(电子版), 2016, 10(05): 527-533.

Committee of experts on antiviral therapy in nucleos(t)ide analogues experienced patients with chronic hepatitis B. Expert consensus on antiviral therapy in nucleos(t)ide analogues experienced patients with chronic hepatitis B: 2016 update[J]. Chinese Journal of Experimental and Clinical Infectious Diseases(Electronic Edition), 2016, 10(05): 527-533.

多数慢性乙型肝炎患者经过核苷(酸)类似物抗病毒治疗后,远期预后可获得显著改善,但仍有部分患者在治疗后发生原发无应答、应答不佳以及复发。为规范慢性乙型肝炎经治患者的再治疗,2013年我们组织国内部分专家讨论并形成了《慢性乙型肝炎核苷(酸)类似物经治患者抗病毒治疗专家共识》。近3年来,符合循证医学原则的研究数据不断增加,对慢性乙型肝炎核苷(酸)类似物(NAs)经治患者抗病毒治疗的认识亦有提高;因此,我们再次组织专家对相关最新资料进行分析整理,形成本共识的2016年更新。

Nucleos(t)ide analogues (NAs) are potent in inhibiting hepatitis B virus replication and improving prognosis in most patients with chronic hepatitis B. But primary non-response, suboptimal response, and relapse may occur in some patients. To optimize the management of NAs experienced patients, the committee for antiviral therapy in nucleos(t)ide analogues experienced patients with chronic hepatitis B published the consensus on antiviral therapy in nucleos(t)ide analogues experienced patients with chronic hepatitis B in 2013. With more and more evidence in management of these patients in the late 3 years, the committee of antiviral therapy in nucleos(t)ide analogues experienced patients with chronic hepatitis B updated the consensus to provide the updated recommendation for management NAs experienced patients.

表1 循证医学证据等级[3,4]
表2 CHB抗病毒治疗原发无应答的定义
表3 CHB相关指南中应答不佳的类似定义
表4 CHB经治复发的定义
1
乙型肝炎病毒耐药专家委员会. 乙型肝炎病毒耐药专家共识: 2009年更新[J]. 中华实验和临床感染病杂志:电子版,2009,3(1):72-79.
2
乙型肝炎病毒耐药讨论专家委员会. 核苷和核苷酸类药物治疗慢性乙型肝炎的耐药及其管理[J]. 中华实验和临床感染病杂志:电子版,2012,6(6):116-123.
3
Guyatt GH, Oxman AD, Vist GE, et al. Rating quality of evidence and strength of recommendations: GRADE: an emerging consensus on rating quality of evidence and strength of recommendations[J]. BMJ,2008,336(7650):924.
4
Shiffman RN, Shekelle P, Overhage JM, et al. Standardized reporting of clinical practice guidelines: a proposal from the Conference on Guideline Standardization[J]. Ann Intern Med,2003,139(6):493-498.
5
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年版)[J/CD]. 中国肝脏病杂志:电子版,2015,7(3):1-18.
6
Lok AS, McMahon BJ. Chronic hepatitis B: update 2009[J]. Hepatology,2009,50(3):661-662.
7
Sarin SK, Kumar M, Lau GK, et al. Asian-Pacific clinical practice guidelines on the management of hepatitis B: a 2015 update[J]. Hepatol Int,2016,10(1):1-98.
8
EASL clinical practice guidelines: Management of chronic hepatitis B virus infection. European Association For The Study Of The Liver[J]. J Hepatol,2012,57(1):167-185.
9
Zoulim F, Perrillo R. Hepatitis B: reflections on the current approach to antiviral therapy[J]. J Hepatol,2008,48 (Suppl 1):S2-S19.
10
Chevaliez S, Rodriguez C, Pawlotsky JM. New virologic tools for management of chronic hepatitis B and C[J]. Gastroenterology,2012,142(6):1303-1313.
11
Wang F, Wang H, Shen H, et al. Evolution of hepatitis B virus polymerase mutations in a patient with HBeAg-positive chronic hepatitis B virus treated with sequential monotherapy and add-on nucleoside/nucleotide analogues[J]. Clin Ther,2009,31(2):360-366.
12
吴珍萍,韩涛,高英堂, 等. 拉米夫定耐药后序贯治疗中HBV准种的演变[J]. 世界华人消化杂志,2010,18(8):779-785.
13
刘霖,汤影子,李俊刚, 等. 拉米夫定与恩替卡韦序贯治疗中的乙型肝炎病毒准种动力学[J]. 中华肝脏病杂志,2010,18(6):423-427.
14
Chen L, Zhang Q, Yu DM, et al. Early changes of hepatitis B virus quasispecies during lamivudine treatment and the correlation with antiviral efficacy[J]. J Hepatol,2009,50(5):895-905.
15
Liu F, Chen L, Yu DM. Evolutionary patterns of hepatitis B virus quasispecies under different selective pressures: correlation with antiviral efficacy[J]. Gut,2011,60(9):1269-1277.
16
Lampertico P, Vigano M, Manenti E, et al. Low resistance to adefovir combined with lamivudine: a 3-year study of 145 lamivudine-resistant hepatitis B patients[J]. Gastroenterology,2007,133(5):1445-1451.
17
Keeffe EB, Zeuzem S, Koff RS, et al. Report of an international workshop: roadmap for management of patients receiving oral therapy for chronic hepatitis B[J]. Clin Gastroenterol Hepatol,2007,5(8):890-897.
18
替比夫定中国路线图专家讨论组. 替比夫定治疗慢性乙型肝炎中国路线图[J]. 中华肝脏病杂志,2008,16(5):323-325.
19
Liaw YF. On-treatment outcome prediction and adjustment during chronic hepatitis B therapy: now and future[J]. Antivir Ther,2009,14(1):13-22.
20
Lai CL, Gane E, Liaw YF, et al. Telbivudine versus lamivudine in patients with chronic hepatitis B[J]. N Engl J Med,2007,357(25):2576-2588.
21
Chae HB, Kim MJ, Seo EG. High efficacy of adefovir and entecavir combination therapy in patients with nucleoside-refractory hepatitis B[J]. Korean J Hepatol,2012,18(1):75-83.
22
Liang LB, Chen LL, Chen EQ, et al. Genotypic resistance profiles in Chinese patients with chronic hepatitis B virus infection and the efficacy of nucleoside analog rescue therapy[J]. Ther Clin Risk Manag,2015,11:417-423.
23
Baran B, Soyer OM, Ormeci AC, et al. Efficacy of tenofovir in patients with lamivudine failure is not different from that in nucleoside/nucleotide analogue-naïve patients with chronic hepatitis B[J]. Antimicrob Agents Chemother,2013,57(4):1790-1796.
24
Park JH, Jung SW, Park NH, et al. Efficacy of tenofovir-based rescue therapy in lamivudine-resistant chronic hepatitis B patients with failure of lamivudine and adefovir combination[J]. Clin Ther,2015,37(7):1433-1442.
25
Tenney DJ, Rose RE, Baldick CJ, et al. Long-term monitoring shows hepatitis B virus resistance to entecavir in nucleoside-naïve patients is rare through 5 years of therapy[J]. Hepatology,2009 49(5):1503-1514.
26
Nguyen NH, Trinh HN, Nguyen TT, et al. Safety and efficacy of entecavir in adefovir-experienced patients[J]. J Gastroenterol Hepatol,2015,30(1):43-50.
27
李兰娟,侯金林. 核苷(酸)类药物联合治疗慢性乙型肝炎专家建议[J]. 中华临床感染病杂志,2011,4(2):65-68.
28
Hou J, Sun J, Xie Q, et al. Virological breakthrough and genotypic resistance in a roadmized, controlled, study on telbivudine treatment applying roadmap concept in CHB: W76 interim analysis of effort study[J]. J Hepatol,2012,56(Supp1 2):S203-S204.
29
Piratvisuth T, Komolmit P, Tanwandee T, et al. 1-year results of telbivudine roadmap study demonstrated maximizing antiviral efficacy and minimizing resistance in HBeAg positive chronic hepatitis B patients[C]. 2011. EASL.
30
Chen EQ, Zhou TY, Bai L, et al. Lamivudine plus adefovir or telbivudine plus adefovir for chronic hepatitis B patients with suboptimal response to adefovir[J]. Antivir Ther,2012,17(6):973-979.
31
Levrero M, Cimino L, Lampertico P, et al. OptiB--a multicenter prospective open label study on tenofovir for chronic hepatitis B patients with suboptimal response to adefovir or ADV/LAM treatment[C]. 2011. EASL.
32
Chang TT, Gish RG, de Man R, et al. A comparison of entecavir and lamivudine for HBeAg-positive chronic hepatitis B. N Engl J Med,2006,354(10):1001-1010.
33
Marcellin P, Heathcote EJ, Buti M, et al. Tenofovir disoproxil fumarate versus adefovir dipivoxil for chronic hepatitis B. N Engl J Med,2008,359(23):2442-2455.
34
Lok AS, Trinh H, Carosi G, et al. Entecavir (ETV) monotherapy for 96 weeks is comparable to combination therapy with ETV plus tenofovir[J]. J Clin Gastroenterol,2016,50(4):338-344.
35
Peng J, Cao J, Yu T, et al. Predictors of sustained virologic response after discontinuation of nucleos(t)ide analog treatment for chronic hepatitis B[J]. Saudi J Gastroenterol,2015,21(4):245-253.
36
Lu J, Li J, Liu Y, et al. Study on Post-treatment relapse in HBeAg positive CHB patients[J]. PLoS One,10(11):e0141072.
37
胡伯斌,江建宁,付嘉鑫, 等. HBeAg阳性慢性乙型肝炎患者经核苷和核苷酸类药物治疗达标停药后复发的相关因素[J]. 临床肝胆病杂志,2016,32(5):885-889.
38
Reijnders JG, Perquin MJ, Zhang N, et al. Nucleos(t)ide analogues only induce temporary hepatitis B e antigen seroconversion in most patients with chronic hepatitis B[J]. Gastroenterology,2010,139(2):491-498.
39
van Nunen AB, Hansen BE, Suh DJ, et al. Durability of HBeAg seroconversion following antiviral therapy for chronic hepatitis B: relation to type of therapy and pretreatment serum hepatitis B virus DNA and alanine aminotransferase[J]. Gut,2003,52(3):420-424.
40
Song BC, Suh DJ, Lee HC, et al. Hepatitis B e antigen seroconversion after lamivudine therapy is not durable in patients with chronic hepatitis B in Korea[J]. Hepatology,2000,32(4 Pt 1):803-806.
41
Dienstag JL, Cianciara J, Karayalcin S, et al. Durability of serologic response after lamivudine treatment of chronic hepatitis B[J]. Hepatology,2003,37(4):748-755.
42
Yoon SK, Jang JW, Kim CW, et al. Long-term results of lamivudine monotherapy in Korean patients with HBeAg-positive chronic hepatitis B: response and relapse rates, and factors related to durability of HBeAg seroconversion[J]. Intervirology,2005,48(6):341-349.
43
Shin JW, Park NH, Park JH, et al. Efficacy of lamivudine re-treatment for relapsed patients after an initial lamivudine therapy in HBeAg-positive chronic hepatitis B[J]. J Viral Hepat,2005,12(4):393-397.
44
Fung J, Lai CL, Yuen J, et al. Randomized trial of lamivudine versus entecavir in entecavir-treated patients with undetectable hepatitis B virus DNA: outcome at 2 years[J]. Hepatology,2011,53(4):1148-1153.
45
Wang Z, Wu XL, Zeng WZ, et al. Lamivudine plus adefovir is a good option for chronic hepatitis B patients with viral relapse after cessation of lamivudine treatment[J]. Virol J,2011,8:388.
46
万谟彬,翁心华. 拉米夫定优化治疗慢性乙型肝炎专家共识[J]. 中华传染病杂志,2012,30(7):387-390.
[1] 高建松, 陈晓晓, 冯婷, 包剑锋, 魏淑芳, 潘林. 基于超声瞬时弹性成像的多参数决策树模型评估慢性乙型肝炎患者肝纤维化等级[J]. 中华医学超声杂志(电子版), 2023, 20(09): 923-929.
[2] 吴方园, 孙霞, 林昌锋, 张震生. HBV相关肝硬化合并急性上消化道出血的危险因素分析[J]. 中华普外科手术学杂志(电子版), 2024, 18(01): 45-47.
[3] 阿冲罗布, 陈颖, 谢德坤. 腹腔镜外囊完整剥离术治疗肝包虫病效果及对患者肝功能、预后的影响[J]. 中华普外科手术学杂志(电子版), 2023, 17(06): 666-669.
[4] 崔占斌, 乔军利, 张丽丽, 韩明强. 尿碘水平与甲状腺乳头状癌患者术后复发危险度分层的相关性[J]. 中华普外科手术学杂志(电子版), 2023, 17(06): 615-618.
[5] 陈垚, 徐伯群, 高志慧. 改良式中间上入路根治术治疗甲状腺癌的有效性安全性研究[J]. 中华普外科手术学杂志(电子版), 2023, 17(06): 619-622.
[6] 邢晓伟, 刘雨辰, 赵冰, 王明刚. 基于术前腹部CT的卷积神经网络对腹壁切口疝术后复发预测价值[J]. 中华疝和腹壁外科杂志(电子版), 2023, 17(06): 677-681.
[7] 姜明, 罗锐, 龙成超. 闭孔疝的诊断与治疗:10年73例患者诊疗经验总结[J]. 中华疝和腹壁外科杂志(电子版), 2023, 17(06): 706-710.
[8] 张文华, 陶焠, 胡添松. 不同部位外生型肝癌临床病理特点及其对术后肝内复发和预后影响[J]. 中华肝脏外科手术学电子杂志, 2023, 12(06): 651-655.
[9] 何吉鑫, 杨燕妮, 王继伟, 李建国, 谢铭. 肠道菌群及肠道代谢产物参与慢性便秘发生机制的研究进展[J]. 中华结直肠疾病电子杂志, 2023, 12(06): 495-499.
[10] 张政赢, 鞠阳, 刘晓宁. 二甲双胍对2型糖尿病患者大肠腺瘤术后复发的影响[J]. 中华消化病与影像杂志(电子版), 2023, 13(06): 485-488.
[11] 易成, 韦伟, 赵宇亮. 急性肾脏病的概念沿革[J]. 中华临床医师杂志(电子版), 2023, 17(08): 906-910.
[12] 周婷, 孙培培, 张二明, 安欣华, 向平超. 北京市石景山区40岁及以上居民慢性阻塞性肺疾病诊断现状调查[J]. 中华临床医师杂志(电子版), 2023, 17(07): 790-797.
[13] 孔凡彪, 杨建荣. 肝脏基础疾病与结直肠癌肝转移之间关系的研究进展[J]. 中华临床医师杂志(电子版), 2023, 17(07): 818-822.
[14] 孙培培, 张二明, 时延伟, 赵春燕, 宋萍萍, 张硕, 张克, 周玉娇, 赵璨, 闫维, 吴蓉菊, 宋丽萍, 郭伟安, 马石头, 安欣华, 包曹歆, 向平超. 北京市石景山区40岁及以上居民慢性阻塞性肺疾病患病情况及相关危险因素分析[J]. 中华临床医师杂志(电子版), 2023, 17(06): 711-719.
[15] 符梅沙, 周玉华, 李慧, 薛春颜. 淋巴细胞免疫治疗对复发性流产患者外周血T淋巴细胞亚群分布与PD1/PD-L1表达的影响及意义[J]. 中华临床医师杂志(电子版), 2023, 17(06): 726-730.
阅读次数
全文


摘要