干扰素α治疗慢性丙型肝炎干扰素中和抗体的产生及其对抗病毒治疗疗效的影响

张文杰; 李朝霞; 田淑菊; 毛维武; 龚晏萱; 屈延

干扰素α治疗慢性丙型肝炎干扰素中和抗体的产生及其对抗病毒治疗疗效的影响

甘肃省第二人民医院感染科

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中图分类号: R512.63
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出版历程
- 出版日期: 2010-01-20

Generation of neutralizing anti-interferon antibodies and its influence on the interferon-alpha (IFN-alpha) treatment for chronic hepatitis C

摘要

摘要: 目的探讨干扰素中和抗体的产生与干扰素治疗慢性丙型肝炎临床疗效的关系。方法纳入92例初治慢性丙型肝炎患者,应用干扰素α-1b（IFNα-1b）、聚乙二醇化干扰素α-2a（PegIFNα-2a）开始（48-72）周的抗病毒治疗,用酶免疫法（EIA）检测治疗前及治疗不同时期血清中的干扰素总抗体,同时应用抗病毒中和生物鉴定法（ANB）检测干扰素中和抗体（NA）。结果92例患者中共有16例出现NA阳性,阳性率为17.39%,反弹组干扰素中和抗体的阳性率明显高于完全应答组（P<0.05）,而难治性丙肝患者中和抗体阳性率亦明显高于完全应答组（P<0.05）。多元Logistic回归分析显示,治疗前HCVRNA水平为NA阳性的影响因素。结论临床应用干扰素治疗慢性丙型肝炎患者出现反弹与NA阳性率显著相关。干扰素中和抗体的产生可能是导致难治性丙肝产生的因素之一。
- 慢性丙型肝炎 /
- 聚乙二醇化干扰素 /
- 干扰素中和抗体 /
- 难治性丙肝
Abstract: Objective The aim of this study was to evaluate the relationship between neutralizing antibodies to interferonalpha and its effect on the interferon antiviral treatment in patients with chronic hepatitis C.Methods The total anti-IFN Ab and neutralizing antibodies (NA) were detected by enzyme immunoassay (EIA) and antiviral neutralizing bioassay (ANB) , respectively.The antibodies were measured in the serum of 92 patients with chronic hepatitis C before treatment and in different periods during the treatment with IFN-α1b or PegIFNα-2a.Results Of the 92 patients, 16 were positive for NA during the treatment course, resulting in an overall NA occurrence rate of 17.39% .The positive rates of NA were significantly higher in group of responders with breakthrough than the group with sustained virological response (SVR) (P <0.05) ;meanwhile, the NA incidence rate was significantly higher in difficult-to-treat population in Hepatitis C than the group of SVR (P < 0.05) .Multinomial logistic regression analysis showed a positive correlation between the positive rates of NA and pretreatment HCV RNA level.Conclusion The phenomenon of break through during antiviral therapy with IFN-α seems to be an obvious consequence of anti-IFN neutralizing antibody.The development of NA may be one of the factors for difficult-to-treat population in Hepatitis C.
- Chronic hepatitis C /
- interferon /
- anti-interferon antibodies /
- neutralizing antibodies

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参考文献(23)

[1]李家斌, 姚阳, 李旭, 等.干扰素抗体产生规律性及对疗效影响初探[J].中华实验和临床病毒学杂志, 2000, 14 (2) ∶196-197.

[2]Jorns C, Holzinger D, Thimme R, et al.Rapid and simple detection of IFN-neutralizing antibodies in chronic hepatitis C non-respon-sive to IFN-alpha[J].J Med Virol, 2006, 78 (1) ∶74-82.

[3]Hou C, Chuang WL, Yu ML, et al.Incidence and associated factors of neutralizing anti-interferon antibodies among chronic hepatitis C patients treated with interferon in Taiwan[J].Scand J Gastroenterol, 2000, 35 (12) ∶1288-1293.

[4]白菡, 赵桂珍, 王贺玲, 等.干扰素治疗慢性丙型肝炎中出现反跳与干扰素抗体关系的研究[J].中国医科大学学报, 2001, 30 (4) ∶285-287.

[5]Arai K, Shindo M, Okuno T.Anti-interferon antibody in chronic hepatitis C[J].Nippon Rinsho, 1994, 52 (7) ∶1929-1934.

[6]Giannelli G, Antonelli G, Fera G, et al.Biological and clinical sig-nificance of neutralizing and binding antibodies to interferon-alpha (IFN-alpha) during therapy for chronic hepatitis C[J].Clin Exp Immunol, 1994, 97 (1) ∶4-9.

[7]Milella M, Antonelli G, Santantonio T, et al.Neutralizing antibodies to recombinant alpha-interferon and response to therapy in chronic hepatitis C virus infection[J].Liver, 1993, 13 (3) ∶146-150.

[8]李智伟, 刘沛, 白菡, 等.干扰素与病毒唑联合治疗慢性丙型肝炎疗效及与干扰素抗体关系的探讨[J].中国实用内科杂志, 2002, 22 (7) ∶399-40.

[9]Antonelli G, Giannelli G, Currenti M, et al.Antibodies to interferon (IFN) in hepatitis C patients relapsing while continuing recombinant IFN-alpha2therapy[J].Clin Exp Immunol, 1996, 104 (3) ∶384-387.

[10]Habu D, Mizuno M, Ohnishi K, et al.The influence of anti-in-terferon-alpha2a antibodies in initial daily four-week interferon-alpha2a therapy for chronic hepatitis C[J].Nippon Shokakibyo Gakkai Zasshi, 1997, 94 (5) ∶319-327.

[11]赵湘平, 邓万芳.观察丙型肝炎患者用干扰素治疗中干扰素抗体对疗效的影响[J].临床和实验医学杂志, 2006, 5 (3) ∶279.

[12]Leroy V, Baud M, de Traversay C, et al.Role of anti-interferon antibodies in breakthrough occurrence during alpha2a and2b therapy in patients with chronic hepatitis C[J].J Hepatol, 1998, 28 (3) ∶375-381.

[13]王健, 李朝品, 贾夫洋, 等.慢性丙肝患者血清干扰素抗体检测及其临床意义[J].山东医药, 2003, 43 (10) ∶1-3.

[14]Boo I, Fischer A E, Johnson D, et al.Neutralizing antibodies in pa-tients with chronic hepatitis C infection treated with (Peg) -inter-feron/ribavirin[J].J Clin Virol, 2007, 39 (4) ∶288-294.

[15]陈青锋, 郭振华, 杨彦麟, 等.慢性丙型肝炎干扰素抗体及血清分型与派罗欣疗效关系探讨[J].国际流行病学传染病学杂志, 2006, 33 (4) ∶232-234.

[16]陈青锋, 郭振华, 肖萍, 等.甘肃地区HCV血清分型与基因分型及干扰素抗体关系研究[J].国际检验医学杂志, 2006, 27 (7) ∶612-614.

[17]Ford JA, Cheong-Lee C.The role of hepatology nurse in the diffi-cult-to-treat hepatitis C population[J].Can J Gastroenterol, 2007, 21 (6) ∶353-354.

[18]Zeuzem S.Difficult-to-treat patients with chronic hepatitis C[J].Praxis, 2006, 95 (38) ∶1459-64.

[19]Bonetti P, Diodati G, Drago C, et al.Interferon antibodies in pa-tients with chronic hepatitic C virus infection treated with recombi-nant interferon alpha-2alpha[J].J Hepatol, 1994, 20 (3) ∶416-420.

[20]毛乾国, 骆抗先, 张明霞, 等.重组α-干扰素治疗慢性乙型肝炎时干扰素中和抗体的产生及影响因素[J].第一军医大学学报, 2003, 23 (12) ∶1319-1322.

[21]童福易, 唐永煌, 白敬羽, 等.病毒性肝炎患者α-干扰素中和抗体发生率及其时间规律的研究[J].临床肝胆病杂志, 1999, 15 (1) ∶38-40.

[22]陈慧.不同亚型干扰素抗体对乙型肝炎病毒疗效的影响[J].肝脏, 2003, 8 (4) ∶33.

[23]Bonino F, Baldi M, Negro F, et al.Clinical relevance of anti-in-terferon antibodies in the serum of chronic hepatitis C patients trea-ted with interferon-alpha[J].J Interferon Cytokine Res, 1997, 17 (1) ∶35-38.

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