长期口服恩替卡韦治疗的慢性乙型肝炎患者换用α干扰素治疗临床疗效随访研究

doi:10.3969/j.issn.1672-5069.2018.05.017

实用肝脏病杂志 ›› 2018, Vol. 21 ›› Issue (5): 721-724.doi: 10.3969/j.issn.1672-5069.2018.05.017

长期口服恩替卡韦治疗的慢性乙型肝炎患者换用α干扰素治疗临床疗效随访研究

王芳芳, 张国范, 郭春霞, 杨振浩, 潘延凤, 余祖江

473000河南省南阳市南阳医学高等专科学校第一附属医院感染性疾病科（王芳芳,张国范,郭春霞,杨振浩）; 郑州大学第一附属医院感染病科（潘延凤,余祖江）

收稿日期:2017-12-20 出版日期:2018-09-10 发布日期:2018-09-27
通讯作者: 张国范,E-mail:375199288@qq.com
作者简介:王芳芳，女，硕士研究生，主治医师。E-mail:375199288@qq.com

Clinical efficacy and safety of switching from entecavir to interferon-α in patients with hepatitis B

Wang Fangfang, Zhang Guofan, Guo Chunxia, et al.

Department of Infectious Diseases,First Affiliated Hospital,Nanyang Medical College,Nanyang 473000,Henan Province,China

Received:2017-12-20 Online:2018-09-10 Published:2018-09-27

摘要/Abstract

摘要： 目的对长期口服恩替卡韦治疗的慢性乙型肝炎（CHB）患者换用干扰素治疗,为临床上针对长期口服核苷（酸）类似物的CHB患者提供一种可行的安全停药方案。方法长期口服恩替卡韦治疗的CHB患者120例,接受恩替卡韦治疗时间为7~11（8.4±2.6）年。60例观察组患者采取口服恩替卡韦与注射重组人干扰素α2b联合治疗12 w,然后单独应用干扰素α2b至48 w,而60例对照组则继续口服恩替卡韦至48 w。两组均随访观察24 w。结果在停药随访24 w时,观察组病毒学复发率为11.7%,生化学复发率为8.3%,黄疸发生率为1.7%,均显著低于对照组的65.0%、43.3%和13.3%（P<0.05）;观察组血清HBsAg和HBeAg转阴率分别为18.3%和21.7%,而对照组无血清HBsAg和HBeAg阴转病例（0.0%和0.0%,P<0.05）;观察组血清HBV DNA复阳10例(16.7%),显著低于对照组的42例（70.0%,P<0.05）;治疗前,两组血清HBsAg水平无显著性差异（P>0.05）,而在治疗24 w、48 w和停药24 w时,观察组血清HBsAg水平分别为（1944.7±268.6）IU/ml、（530.7±261.3）IU/ml和（512.4±176.7）IU/ml, 均显著低于对照组【（3080.4±255.1）IU/ml、（3087.1±264.1）IU/ml和（3148.5±212.3）IU/ml,P<0.01】。结论针对长期口服恩替卡韦治疗有停药要求的CHB患者,在给予人干扰素α2b巩固治疗后,可在严密观察下停药,临床预后比较好。

关键词: 慢性乙型肝炎, 恩替卡韦, α-干扰素, 安全停药

Key words: Chronic hepatitis B, Entecavir, Interferon α, Safe discontinuation

王芳芳, 张国范, 郭春霞, 杨振浩, 潘延凤, 余祖江. 长期口服恩替卡韦治疗的慢性乙型肝炎患者换用α干扰素治疗临床疗效随访研究[J]. 实用肝脏病杂志, 2018, 21(5): 721-724.

Wang Fangfang, Zhang Guofan, Guo Chunxia, et al.. Clinical efficacy and safety of switching from entecavir to interferon-α in patients with hepatitis B[J]. JOURNAL OF PRACTICAL HEPATOLOGY, 2018, 21(5): 721-724.

参考文献

[1] 中华医学会肝病学分会和感染病学分会. 慢性乙型肝炎防治指南(2015 更新版).实用肝脏病杂志,2016,19(3):Ⅴ-XXⅢ.
[2] Geneva:World Health Organization. Guidelines for the prevention,care and treatment of persons with chronic hepatitis B infection. Free Books & Documents,2015.
[3] Yapali S,Talaat N,Lok AS.Management of hepatitis B:our practice and how it relates to the guidelines. Clin Gastroenterol Hepatol,2014,12(1):16-26.
[4] Liaw YF,Sung JJ,Chow WC,et al.Lamivudine for patients with chronic hepatitis B and advanced liver disease. N Engl J Med,2004,351(15):1521-1531.
[5] Marcellin P,Gane E,Buti M,et al.Regression of cirrhosis during treatment with tenofovir disoproxil fumarate for chronic hepatitis B:a 5-year open-label follow-up study. Lancet,2013,381(9865):468-475.
[6] 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. Gastroenterology,2010,139(2):491-498.
[7] Jeng WJ,Sheen IS,Chen YC,et al.Off-therapy durability of response to entecavir therapy in hepatitis B e antigen-negative chronic hepatitis B patients. Hepatology,2013,58(6):1888-1896.
[8] Seto WK,Hui AJ,Wong VW,et al.Treatment cessation of entecavir in Asian patients with hepatitis B e antigen negative chronic hepatitis B:a multicentre prospective study. Gut,2015,64(4):667-672.
[9] 周岳进,郑金莉, 肖扬等. 拉米夫定治疗CHB患者停药后病情加重的综合处理. 实用肝脏病杂志,2003,6(4):237-238.
[10] Nicole A,Weerd D,Nguyen T.The interferons and their receptors-distribution and regulation. Immunol Cell Biol,2012,90(5):483-491.
[11] Liaw YF,Kao JH,Piratvisuth T,et al.Asian-Pacific consensus statement on the management of chronic hepatitis B:a 2012 update. Hepatol Int,2012,6(3):531-561.
[12] Michailidis E,Kirby KA,Hachiya A,et al.Antiviral therapies: focus on hepatitis B reverse transcriptase. Int J Biochem Cell Biol,2012,44(7):1060-1071.
[13] Ji M,Hu K.Recent advances in the study of hepatitis B virus covalently closed circular DNA. Virol Sin,2017,32(6):454-464.
[14] Schreiner S,Nassal M.A role for the host DNA damage response in hepatitis B virus cccDNA formation-and beyond. Viruses,2017,9:125.
[15] Zeisel MB,Lucifora J,Mason WS,et al.Towards an HBV cure: state of-the-art and unresolved questions-report of the ANRS workshop on HBV cure. Gut,2015,64:1314-1326.
[16] Nassal M.HBV cccDNA:viral persistence reservoir and key obstacle for a cure of chronic hepatitis B. Gut,2015,64:1972-1984.
[17] Lu F,Wang J,Chen X,et al.Potential use of serum HBV RNA in antiviral therapy for chronic hepatitis B in the era of nucleos(t)ide analogs. Front Med,2017,11(4):502-508.
[18] Wang J,Sheng Q,Ding Y,et al.HBV RNA virion-like particles produced under nucleos(t)ide analogues treatment are mainly replication-deficient. J Hepatol,2017,78(17):324-331.
[19] van Campenhout MJH,van Bmmel F,Pfefferkorn M,et al. Host and viral factors associated with serum hepatitis B virus RNA levels among patients in need for treatment. Hepatology,2018[Epub ahead of print].
[20] Pei RJ,Chen XW Lu MJ. Control of hepatitis B virus replication by interferons and Toll-like receptor signaling pathways. World J Gastroenterol,2014,20(33):11618-11629.
[21] Haller O,Staeheli P,Kochs G.Interferon-induced Mx proteins in antiviral host defense. Biochimie,2007,89:812-818.
[22] Samuel CE.Antiviral actions of interferons. Clin Microbiol Rev,2001,14:778-809.
[23] Lucifora J,Xia Y,Reisinger F,et al.Specific and nonhepatotoxic degradation of nuclear hepatitis B virus cccDNA. Science,2014,343:1221-1228.
[24] Biron,CA.Role of early cytokines, including alpha and beta interferons IFN-(α/β),in innate and adaptive immune responses to viral infections. Semin Immunol,2016,5:383-390.
[25] Martinot-Peignoux M,Lapalus M,Asselah T,et al.HBsAg quantification:useful for monitoring natural history and treatment outcome. Liver Int,2014,34(Suppl 1):97-107.
[26] Belloni L,Allweiss L,Guerrieri F,et al.IFN-α inhibits HBV transcription and replication in cell culture and in humanized mice by targeting the epigenetic regulation of the nuclear cccDNA minichromosome. J Clin Invest,2012,122:529-537.

长期口服恩替卡韦治疗的慢性乙型肝炎患者换用α干扰素治疗临床疗效随访研究

Clinical efficacy and safety of switching from entecavir to interferon-α in patients with hepatitis B

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