[重组α干扰素治疗慢性乙型肝炎患者中中和性抗干扰素抗体的临床意义]

[Clinical significance of neutralizing anti-interferon antibodies in chronic hepatitis B patients treated with recombinant interferon-alpha].

作者信息

Mao Qian-guo, Luo Kang-xian, Liu Ding-li, Zhang Ming-xia, Hou Jin-lin

机构信息

Department of Infectious Diseases, Nanfang Hospital, the First Military Medical University, Guangzhou 510515, China.

出版信息

Zhonghua Gan Zang Bing Za Zhi. 2004 Apr;12(4):205-7.

PMID:15099466

Abstract

OBJECTIVE

To investigate the clinical significance of neutralizing anti-interferon-alpha antibodies (NA) in chronic hepatitis B patients treated with recombinant interferon-alpha(rIFN-alpha).

METHODS

One hundred and eighty-one patients (128 male and 53 female) with histological proven chronic hepatitis B were treated with 5 MU recombinant interferon-alpha 1b (rIFN-alpha 1b) subcutaneously thrice weekly for 6 to 37 (median 10) months. For each patient, Specific detection of serum HBV DNA level with fluorescent-quantitative PCR, HBeAg with enzymoimmunoassay and NA with an antiviral neutralizing biological assay were performed during therapy.

RESULTS

NA was found in 61 (33.7%) of 181 patients. At the end of treatment, complete-response was achieved in 17 (27.9%) of 61 patients with NA and in 54 (45.0%) of 120 patients without NA, respectively (chi2=4.979). For NA positive patients, the complete-response rate was significantly lower in those who had not achieved partial-response prior to or at the same time as NA occurred than in those who did (3.8%, 1/26, vs. 45.7%, 16/35, chi2 = 7.457). Moreover, it was lower in patients who either had 20pg/ml of serum HBV DNA or above or HBV DNA had being reduced by less than 60% recent 3 months, but higher in those who had less than 20pg/ml of HBV DNA and HBV DNA had being reduced by 60% or above (20.0%, 9/45, vs. 56.3%, 9/16, chi2 = 11.009).

CONCLUSION

NA may negate the antiviral effects of rIFN-alpha in chronic hepatitis B patients treated with rIFN-alpha, especially if they appear before partial-response or at the occasion at which serum HBV DNA level was not below 20pg/ml or HBV DNA had being reduced by less than 60% recent 3 months.

摘要

目的

探讨在接受重组干扰素-α（rIFN-α）治疗的慢性乙型肝炎患者中，中和性抗干扰素-α抗体（NA）的临床意义。

方法

181例经组织学证实的慢性乙型肝炎患者（男128例，女53例），接受5MU重组干扰素-α1b（rIFN-α1b）皮下注射，每周3次，共治疗6至37（中位10）个月。治疗期间，对每位患者采用荧光定量PCR特异性检测血清HBV DNA水平，采用酶免疫法检测HBeAg，采用抗病毒中和生物学检测法检测NA。

结果

181例患者中，61例（33.7%）检测到NA。治疗结束时，61例有NA的患者中17例（27.9%）获得完全应答，120例无NA的患者中54例（45.0%）获得完全应答（χ2=4.979）。对于NA阳性患者，在NA出现之前或同时未达到部分应答的患者的完全应答率显著低于达到部分应答的患者（3.8%，1/26，对45.7%，16/35，χ2=7.457）。此外，血清HBV DNA水平≥20pg/ml或近3个月内HBV DNA下降<60%的患者完全应答率较低，而HBV DNA<20pg/ml且近3个月内HBV DNA下降≥60%的患者完全应答率较高（20.0%，9/45，对56.3%，9/16，χ2=11.009）。