聚乙二醇干扰素α-2a治疗非活动性HBsAg携带者HBsAg清除与血清粒-巨噬细胞集落刺激因子水平的关系

曹振环; 鲁俊锋; 武亚丽; 郑燕红; 陈新月

doi:10.3969/j.issn.1001-5256.2018.05.015

聚乙二醇干扰素α-2a治疗非活动性HBsAg携带者HBsAg清除与血清粒-巨噬细胞集落刺激因子水平的关系

DOI: 10.3969/j.issn.1001-5256.2018.05.015

首都医科大学附属北京佑安医院

基金项目:

“十三五”国家重大科技专项(2017ZX10202201)；首都临床特色应用研究(Z161100000516018);首都临床特色应用研究(Z171100001017062)；首都卫生发展科研重点专项项目(首发2016-1-2183)；北京市自然科学基金(7182073)；首都卫生发展科研专项(首发2018-2-2183)；北京市医院管理局青年人才培养“青苗”计划(QML20161701)；北京市教委科技发展基金(11720674)；

详细信息

中图分类号: R512.62
计量
- 文章访问数: 2184
- HTML全文浏览量: 12
- PDF下载量: 406
- 被引次数: 0
出版历程
- 收稿日期: 2017-11-20
- 出版日期: 2018-05-20

Association between HBsAg clearance and serum level of granulocyte-macrophage colony stimulating factor in inactive HBsAg carriers receiving pegylated interferon alpha-2a

Beijing YouAn Hospital, Capital Medical University

Research funding:

摘要

摘要: 目的探讨聚乙二醇干扰素（PEG-IFN）α-2a治疗非活动性HBs Ag携带者（IHC）发生HBs Ag清除与血清粒-巨噬细胞集落刺激因子（GM-CSF）水平的关系。方法收集2013年1月-2016年1月就诊于首都医科大学附属北京佑安医院门诊的IHC患者20例,经PEG-IFNα-2a治疗24周后13例获得HBs Ag清除（R组）,7例未获得HBs Ag清除（NR组）。用Luminex技术检测患者基线、治疗12周和治疗24周血清GM-CSF水平。同时检测11例健康人（HC组）血清GM-CSF水平。计量资料2组间比较采用t检验,多组间比较采用方差分析,进一步两两比较采用Bonferroni检验。计数资料组间比较采用χ2检验。结果 R组、NR组及HC组基线血清GM-CSF水平分别为（42.63±11.24）pg/ml、（46.77±10.52）pg/ml（11.97±3.85）pg/ml,3组之间比较差异具有统计学意义（F=4.482,P=0.02）,R组与NR组GM-CSF水平均明显高于HC组（P值均<0.05）。PEG-IFNα-2a治疗后12周和24周,R组血清GM-CSF水平...
- 肝炎病毒,乙型 /
- 肝炎表面抗原,乙型 /
- 聚乙烯二醇类 /
- 干扰素类 /
- 粒细胞巨噬细胞集落刺激因子
Abstract: Objective To investigate the association between HBs Ag clearance and serum level of granulocyte-macrophage colony stimulating factor ( GM-CSF) in inactive HBs Ag carriers receiving pegylated interferon ( PEG-IFN) alpha-2 a. Methods A total of 20 inactive HBs Ag carriers who visited Beijing You An Hospital, Capital Medical University, from January 2013 to January 2016 were enrolled, and after 24 weeks of PEG-IFN alpha-2 a treatment, 13 achieved HBs Ag clearance ( R group) and 7 did not achieve HBs Ag clearance ( NR group) . The Luminex technique was used to measure the serum level of GM-CSF at baseline and at weeks 12 and 24 of treatment. The serum level of GM-CSF was also measured for 11 healthy controls ( HC group) . The t-test or an analysis of variance was used for comparison of continuous data between groups, and the Bonferroni test was used for further comparison between two groups. The chi-square test was used for comparison of categorical data between groups. Results The R and NR groups had a significantly higher serum GM-CSF level than the HC group ( 42. 63 ±11. 24 pg/ml and 46. 77 ± 10. 52 pg/ml vs 11. 97 ± 3. 85 pg/ml) , and there was a significant difference between the three groups ( F = 4. 482, P = 0. 02) . At weeks 12 and 24 of PEG-IFNα-2 a treatment, the R group had a significantly higher serum GM-CSF level than the NR group ( t = 22. 422 and 17. 782, both P < 0. 05) . In the R group, the serum GM-CSF level was 42. 63 ± 11. 25 pg/ml at baseline, significantly increased to 83. 31 ± 14. 20 pg/ml at week 12 of treatment, and then significantly decreased to 32. 34 ± 8. 06 pg/ml at week 24 of treatment ( F =7. 655, P =0. 002) . In the NR group, the serum GM-CSF level was 46. 77 ± 10. 52 pg/ml at baseline and significantly decreased to25. 90 ± 7. 06 pg/ml at week 12 of treatment and 9. 43 ± 2. 45 pg/ml at week 24 of treatment ( F = 5. 264, P = 0. 016) . Conclusion In inactive HBs Ag carriers receiving PEG-IFN alpha-2 a treatment, the increase in serum GM-CSF level may indicate HBs Ag clearance.
- hepatitis B virus /
- hepatitis b surface antigens /
- polyethylene glycols /
- interferons /
- granulocyte-macrophage colony-stimulating factor

HTML全文

参考文献(21)

[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]TERRAULT NA, BZOWEI NH, CHANG KM, et al.AASLD guidelines for treatment of chronic hepatitis B[J].Hepatology, 2016, 63 (1) :261-283.

[3] 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.

[4]CHU CM, LIAW YF.Spontaneous relapse of hepatitis in inactive HBs Ag carriers[J].Hepatol Int, 2007, 1 (2) :311-315.

[5]CHEN JD, YANG HI, IIOEIE UH, et al.Carriers of inactive hepatitis B virus are still at risk for hepatocellular carcinoma and liverrelated death[J].Gastroenterology, 2010, 138 (5) :1747-1754.

[6]CHUNG SJ, KIM JK, PARK MC, et al.Reactivation of hepatitis B viral infection in inactive HBs Ag carriers following anti-tumor necrosis factor-alpha therapy[J].J Rheumatol, 2009, 36 (11) :2416-2420.

[7]HWANG JP, LOK AS.Management of patients with hepatitis B who require immunosuppressive therapy[J].Nat Rev Gastroenterol Hepatol, 2014, 11 (4) :209-219.

[8]ZHOU K, TERRAULT N.Management of hepatitis B in special populations[J].Best Pract Res Clin Gastroenterol, 2017, 31 (3) :311-320.

[9]CAO Z, LIU Y, MA L, et al.A potent hepatitis B surface antigen response in subjects with inactive hepatitis B surface antigen carrier treated with pegylated-interferon alpha[J].Hepatology, 2017, 66 (4) :1058-1066.

[10]HABERSETZER F, MOENNE-LOCCOZ R, MEYER N, et al.Loss of hepatitis B surface antigen in a real-life clinical cohort of patients with chronic hepatitis B virus infection[J].Liver Int, 2015, 35 (1) :130-139.

[11]OLIVERI F, SURACE L, CAVALLONE D, et al.Long-term outcome of inactive and active, low viraemic HBe Ag negative-hepatitis B virus infection:benign course towards HBs Ag clearance[J].Liver International, 2017, 37 (11) :1622-1631.

[12]GUARDIOLA ARVALO A, GMEZ RODRGUEZ R, ROMERO GUTIRREZ M, et al.Characteristics and course of chronic hepatitis B e antigen-negative infection[J].Gastroenterol Hepatol, 2017, 40 (2) :59-69.

[13]ZACHARAKIS GH, KOSKINAS J, KOTSIOU S, et al.Natural history of chronic HBV infection:a cohort study with up to12 years follow-up in North Greece (part of the Interreg III/EC-project) [J].J Med Virol, 2005, 77 (2) :173-179.

[14]CHU CM, LIAW YF.Incidence and risk factors of progression to cirrhosis in inactive carriers of hepatitis B virus[J].Am J Gastroenterol, 2009, 104 (7) :1693-1699.

[15]WANG X, DONG A, XIAO J, et al.Overcoming HBV immune tolerance to eliminate HBs Ag-positive hepatocytes via pre-administration of GM-CSF as a novel adjuvant for a hepatitis B vaccine in HBV transgenic mice[J].Cell Mol Immunol, 2016, 13 (6) :850-861.

[16]ROOZBEH J, BAGHERI-LANKARANI K, MOHAGHEGH P, et al.A randomized pilot trial on the effect of granulocyte-colony stimulating factor on antibody response in hemodialysis patients who had not responded to routine hepatitis B virus vaccine[J].J Nephropathol, 2015, 4 (1) :13-17.

[17]QING Y, CHEN M, ZHAO J, et al.Construction of an HBV DNA vaccine by fusion of the GM-CSF gene to the HBV-S gene and examination of its immune effects in normal and HBV-transgenic mice[J].Vaccine, 2010, 28 (26) :4301-4307.

[18]YU GD.New regimens for antiviral/immunoregulatory therapy in treatment-naive patients with HBe Ag-positive chronic hepatitis B[D].Hangzhou:Zhejiang Univ, 2016. (in Chinese) 俞国栋.HBe Ag阳性慢性乙型肝炎初治患者抗病毒/免疫调节治疗新方案的研究[D].杭州:浙江大学, 2016.

[19]CAI H.New regimens for antiviral therapy/immunotherapy reduce ccc DNA level in hepatocytes in treatment-naive patients with HBe Ag-positive chronic hepatitis B[D].Hangzhou:Zhejiang Univ, 2016. (in Chinese) 蔡欢.抗病毒/免疫治疗新方案降低HBe Ag阳性慢乙肝初治患者肝细胞ccc DNA水平研究[D].杭州:浙江大学, 2016.

[20] CHI CP.WANG YM, WANG YF, et al.A preliminary study on the clinical effect of IFNα-2b combined with rh GM-CSF in treatment of chronic hepatitis B[C].The 14th National Academic Conference on Interferons and Cytokines, 2004. (in Chinese) 迟春萍, 王玉梅, 王艳芬, 等.IFNα-2b联合rh GM-CSF治疗慢性乙肝的初步临床研究[C].第14次全国干扰素及细胞因子学术会议, 2004.

[21]ZHAO W, ZHOU X, ZHAO G, et al.Enrichment of Ly6Chi monocytes by multiple GM-CSF injections with HBV vaccine contributes to viral clearance in a HBV mouse model[J].Hum Vaccin Immunother, 2017, 13 (12) :2872-2882.

施引文献

资源附件(0)

访问统计