恩替卡韦长疗程后联合或序贯IFNα治疗慢性乙型肝炎的效果与安全性分析

高胜利; 赵刚; 徐密琴; 沈燕; 俞净; 叶杨; 何丽华; 金文娟; 孙桂英; 钮志林

doi:10.3969/j.issn.1001-5256.2018.02.010

恩替卡韦长疗程后联合或序贯IFNα治疗慢性乙型肝炎的效果与安全性分析

DOI: 10.3969/j.issn.1001-5256.2018.02.010

南通大学附属吴江医院感染科

基金项目:

江苏省苏州市吴江区科技计划项目(WS201304)；

详细信息

中图分类号: R512.62
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出版历程
- 出版日期: 2018-02-20

Efficacy and safety of interferon-α given additionally or sequentially after long-term entecavir therapy in treatment of chronic hepatitis B

Department of Infectious Diseases, Wujiang Hospital Affiliated to Nantong University

Research funding:

摘要

摘要:
目的探讨经恩替卡韦（ETV）长期治疗,有效抑制HBV DNA后,采取序贯或联合IFNα治疗与单用ETV治疗的疗效与安全性比较。方法收集2013年1月-2015年12月南通大学附属吴江医院门诊和住院的慢性乙型肝炎患者27例,所有患者已经ETV抗病毒治疗3年或以上,HBV DNA阴性,无IFN治疗禁忌证,将纳入患者随机分为3组,每组9例。对照组:继续ETV治疗;序贯组:更换为IFNα序贯治疗;联合组:联合IFNα治疗。检测治疗0、12、24、36、48周时血清HBV DNA、HBV血清标志物、血常规、肝功能,观察治疗情况,记录结果并进行统计分析。计量资料多组间比较采用单因素方差分析,进一步两两比较采用Scheffe检验。结果无退出研究病例,无严重不良事件发生;序贯组有1例24周后出现了病毒反弹,但无临床症状,肝功能各项生化指标正常。治疗结束时,序贯组和联合组HBsAg下降的绝对值均显著高于对照组（P值均<0.001）;序贯组和联合组各有2例出现了HBsAg的阴转,阴转率22%;对照组未出现HBsAg的阴转病例。结论 ETV有效抑制病毒复制后的IFNα序贯或联合治疗可能是安全的,HBs...
- 肝炎,乙型,慢性 /
- 肝炎表面抗原,乙型 /
- 恩替卡韦 /
- 干扰素α /
- 治疗
Abstract:
Objective To investigate the efficacy and safety of interferon-α (IFN-α) given additionally or sequentially after effective inhibition of HBV DNA by long-term entecavir (ETV) therapy versus ETV alone in the treatment of chronic hepatitis B (CHB) .Methods A total of 27 CHB patients with negative HBV DNA who were admitted to department of infectious diseases in Wujiang Hospital Affiliated to Nantong University from January 2013 to December 2015 had been treated with ETV antiviral therapy for 3 or more years and had no contraindications for IFN-α therapy were enrolled and randomly divided into three groups, with 9 patients in each group.The patients in the control group were given ETV alone, those in sequential group were given IFN-α sequentially after ETV therapy, and those in the combination group were given IFN-α additionally after ETV therapy.Serum HBV DNA, HBV serum markers, routine blood test, and liver function were measured at 0, 12, 24, 36, and 48 weeks of treatment.The patients' treatment outcomes were observed and a statistical analysis was performed.A one-way analysis of variance was used for comparison between multiple groups, and the Scheffe test was used for further comparison between two groups.Results There were not drop-outs, and no patient experienced serious adverse reactions.One patient in the sequential group experienced viral rebound after 24 weeks of treatment without any clinical symptoms and had normal liver function parameters.At the end of treatment, the sequential group and the combination group had a significantly higher absolute value of the reduction in HBsAg than the control group (both P < 0.001) .Two patients each in the sequential group and the combination group achieved HBsAg clearance, resulting in a clearance rate of 22%.No patient in the control group achieved HBsAg clearance.Conclusion IFN-α given additionally or sequentially after effective inhibition by ETV is safe and may achieve a significantly greater reduction in HBsAg than ETV alone.A few patients even achieve clinical cure.
- hepatitis B, chronic /
- hepatitis B surface antigens /
- entecavir /
- interferon-alpha /
- therapy

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参考文献(15)

[1]FOURATI S, PAWLOTSKY JM.Recent advances in understanding and diagnosing hepatitis B virus infection[J].F1000Res, 2016, 5:F1000 Faculty Rev-2243.

[2]TESTONI B, DURANTEL D, ZOULIM F.Novel targets for hepatitis B virus therapy[J].Liver Int, 2017, 37 (Suppl 1) :33-39.

[3]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.

[4]CHENG J.Build confidence and head for a future“with the elimination of hepatitis B”[J/CD].Chin J Liver Dis:Electronic Edition, 2016, 8 (3) :1-4. (in Chinese) 成军.树立信心, 奔向“消灭乙型肝炎”的未来[J/CD].中国肝脏病杂志:电子版, 2016, 8 (3) :1-4.

[5]TAMAI H, IDA Y, SHINGAKI N, et al.Add-on pegylated interferon alpha-2a therapy in chronic hepatitis B Japanese patients treated with entecavir[J].Hepat Res Treat, 2017, 2017:2093847.

[6]LAMPERTICO P, CHAN HL, JANSSEN HL, et al.Review article:long-term safety of nucleoside and nucleotide analogues in HBV-monoinfected patients[J].Aliment Pharmacol Ther, 2016, 44 (1) :16-34.

[7]TAWADA A, KANDA T, YOKOSUKA O.Current and future directions for treating hepatitis B virus infection[J].World J Hepatol, 2015, 7 (11) :1541-1552.

[8]European Association for the Study of the Liver.EASL 2017 clinical practice guidelines on the management of hepatitis B virus infection[J].Hepatol, 2017, 67 (2) :370-398.

[9]YUAN T, JIANG Y, LI M, et al.Chronic hepatitis B surface antigen seroclearance-related immune factors[J].Hepatol Res, 2017, 47 (1) :49-59.

[10]LI YP.Effect ofα-interferon combined with entecavir for chronic hepatitis B[J/CD].Chin J Exp Clin Infect Dis:Electronic Edition, 2017, 16 (12) :1190-1192. (in Chinese) 李亚萍.α-干扰素联合恩替卡韦治疗慢性乙型肝炎的临床效果观察[J/CD].中华实验和临床感染病杂志:电子版, 2017, 16 (12) :1190-1192.

[11]PAYNE RJ, NOWAK MA, BLUMBERG BS.A cellular model to explain the pathogenesis of infection by the hepatitis B virus[J].Math Biosci, 1994, 123 (1) :25-58.

[12]BONHOEFFER S, MAY RM, SHAW GM, et al.Virus dynamics and drug therapy[J].Proc Natl Acad Sci U S A, 1997, 94 (13) :6971-6976.

[13]LU FM, WANG J, CHEN XM, et al.The potential use of serum HBV RNA to guide the functional cure of chronic heptitis B[J].Chin J Hepatol, 2017, 25 (2) :105-110. (in Chinese) 鲁凤民, 王杰, 陈香梅, 等.乙型肝炎病毒RNA病毒样颗粒的发现及其对抗病毒治疗临床实践的潜在影响[J].中华肝脏病杂志, 2017, 25 (2) :105-110.

[14]CHI ZC.Individualized antiviral therapy for chronic hepatitis B[J].J Clin Hepatol, 2010, 26 (1) :4-8. (in Chinese) 池肇春.慢乙肝抗病毒的个体化治疗[J].临床肝胆病杂志, 2010, 26 (1) :4-8.

[15]LI Q, ZHUO QB, HUANG YX, et al.Combination therapy and sequential therapy with interferons and nucleos (t) ide analogues against HBV[J].J Clin Hepatol, 2015, 31 (4) :495-499. (in Chinese) 李强, 卓其斌, 黄玉仙, 等.干扰素与核苷和核苷酸类药物联合或序贯治疗慢性乙型肝炎方案的探讨[J].临床肝胆病杂志, 2015, 31 (4) :495-499.

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