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重组α干扰素治疗慢性乙型肝炎病毒学反弹与干扰素中和抗体的相关性研究 被引量:9

Viral breakthrough and neutralizing anti-interferon antibody production in chronic hepatitis B patients treated with recombinant interferon-alpha
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摘要 目的 观察和分析重组α干扰素(rIFNα)治疗CHB过程中出现病毒学反弹与干扰素中和抗体(NAb)产生的关系。方法 485例经肝穿刺活组织检查证实的CHB患者,给予rIFNα1b治疗,每次5×106U,每周3次,疗程个体化(6-37个月,中位数10个月),疗程中1-3个月检测1次肝功能,并以PCR荧光定量测定HBV DNA、Abbott EIA试剂检测HBeAg、抗病毒生物中和法检测NAb。结果 485例患者中,66例(13.6%)于治疗过程中出现病毒学反弹,NAb阳性98例(20.2%),病毒学反弹组NAb阳性率68.2%(45/66),显著高于未发生病毒学反弹组的12.6%(53/415),差异有统计学意义(x^2=109.06,P〈0.01)。NAb阳性组病毒学反弹的发生率为45.9%(45/98),显著高于NAb阴性组的5.4%(21/387),差异有统计学意义(x^2=109.06, P〈0.01)。病毒学反弹的时间与NAb检出的时间存在相关性及一致性(CR=98.3%,P〈0.01)。多因素分析表明,NAb的检出是病毒学反弹发生的相关因素之一(P〈0.01),患者的年龄和治疗前HBeAg状态亦可影响病毒学反弹的发生。结论 rIFNα治疗CHB过程中病毒学反弹的发生率约13.6%,病毒学反弹的发生与NAb的产生密切相关,患者的年龄和治疗前HBeAg水平亦可影响病毒学反弹的发生。 Objective To investigate the relationship of virological breakthrough and production of neutralizing anti-interferon antibody (NAb) in chronic hepatitis B patients treated with recombinant interferon-alpha (rIFN-alpha). Method Four hundred eighty-five patients with histological proven chronic hepatitis B were treated with 5 MU recombinant interferon-alpha lb (rIFN- α lb) thrice weekly for 6-37 months (median 10). Serum HBV DNA, HBeAg and NAb levels of the patients were detected by fluoresecent-quantitative PCR, enzymoimmunoassay and antiviral neutralizing biological assay respectively during the therapy. Results Virological breakthrough occurred in 66 patients (13.6%), and NAb was found in 98 patients (20.2%) of the total 485 patients. The rate of NAb positivity was higher in patients with viral breakthrough than those without it (68.2%, 45/66, vs 12.6%, 53/419, x^2 = 109.06, P 〈 0.01), and viral breakthrough occurred more in patients with positive NAb than with negative NAb (45.9%, 45/98, vs 5.4%, 21/387, x^2 = 109.06, P 〈 0.01). The time of the viral breakthrough occurrence and the time of NAb production had a significant correlation (P 〈 0.01). The occurrence of viral breakthrough was also influenced by the age of patients (P 〈 0.05) and HBeAg status (P 〈 0.01) before they were treated. Conclusion Viral breakthrough occurred in 13.6% of our 485 chronic hepatitis B patients treated with recombinant interferon-alpha. Their viral breakthrough and production of NAb production had a significant correlation.
出处 《中华肝脏病杂志》 CAS CSCD 北大核心 2007年第6期422-424,共3页 Chinese Journal of Hepatology
关键词 肝炎 乙型 慢性 干扰素I型 重组 抗体 病毒学反弹 Hepatitis B, chronic Interferon type I, recombinant Antibodies Viral rebound
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参考文献7

  • 1中华医学会传染病与,寄生虫病学分会,肝病学分会.病毒性肝炎防治方案[J].中华肝脏病杂志,2000,8(6):324-329. 被引量:14021
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  • 4Leroy V, Baud M, de Traversay C, et al. Role of anti-interferon antibodies in breakthrough occurrence during alpha 2a and 2b therapy in patients with chronic hepatitis C. J Hepatol, 1998, 28: 375-381.
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二级参考文献11

  • 1Lai C L,J Gastroenterol Hepatol,1999年,14卷,增刊,S19页
  • 2Porres JC, Carreno V, Ruiz M, et al. Interferon antibodies in patients with chronic HBV infection treated with recombinant interferon. J Hepatol, 1989, 8: 351-357.
  • 3Lok AS, Lai CL, Leung EK. Interferon antibodies may negate the antiviral effects of recombinant alpha-interferon treatment in patients with chronic hepatitis B virus infection. Hepatology, 1990,12: 1266-1270.
  • 4Leroy V, Baud M, de Traversay C, et al. Role of anti-interferon antibodies in breakthrough occurrence during alpha 2a and 2b therapy in patients with chronic hepatitis C. J Hepatol, 1998, 28: 375-381.
  • 5Stancek D, Fuchsberger N, Oltman M, et al. Significance of antiinterferon-alpha2 and sICAM-1 activities in the sera of viral hepatitis B and C patients treated with human recombinant interferonatpha2. Acta Virol, 2001, 45: 287-292.
  • 6Antonelli G, Simeoni E, Currenti M, et al. Interferon antibodies in patients with infectious diseases. Anti-interferon antibodies.Biotherapy, 1997, 10: 7-14.
  • 7Antonelli G, Currenti M, Turriziani O, et al. Neutralizing antibodies to interferon-alpha. Relative frequency in patients treated with different interferon preparations. J Infect Dis, 199t, 163: 882-885.
  • 8Stancek D, Fuchsberger N, Oltman M, et al. Significance of antiinterferon-alpha2 and sICAM-1 activities in the sera of viral hepatitis B and C patients treated with human recombinant interferonalpha2. Acta Virol, 2001, 45: 287-292.
  • 9许正锯,王崇国,李旭红,杨红,张启华.干扰素抗体与干扰素α-2a治疗慢性乙型肝炎疗效的关系[J].中华传染病杂志,1998,16(3):178-179. 被引量:12
  • 10刘定立,张明霞,冯筱榕,章廉.重组α干扰素治疗慢性病毒性肝炎干扰素中和抗体的产生[J].解放军医学杂志,2000,25(1):14-15. 被引量:7

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