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  

Generation of neutralizing anti-interferon antibodies and factors influencing their production in chronic hepatitis B patients receiving recombinant interferon-alpha treatment

作　　者：毛乾国[1] 骆抗先[1] 张明霞[1] 刘定立[1] 候金林[1] 

机构地区：[1]第一军医大学南方医院感染内科,广东广州510515

出　　处：《第一军医大学学报》2003年第12期1319-1322,共4页Journal of First Military Medical University

摘　　要：目的观察重组α-干扰素(rIFN-α)治疗慢性乙型肝炎时干扰素中和抗体(NA)的发生率、阳性率,并分析影响NA产生的因素.方法对181例经肝穿刺活检证实的慢性乙型肝炎患者给予rIFN-α1b治疗,每次5 MU,每周3次,治疗时间6～37个月(中位数10.0月),自治疗第3个月起至治疗结束以抗病毒生物中和法每1～3个月检测血清NA.结果181例中61例产生NA,发生率33.7%.不同治疗时段发生率无显著性差异,阳性率有显著性差异(χ2=98.051,P=0.000),阳性率与治疗时段正相关(r=0.855,P＜0.001).男性发生率(39.1%)高于女性(20.8%)(χ2=5.622,P＜0.02).二分类Logistic回归分析表明,性别、年龄、肝组织炎症活动度分级、纤维化程度分期、丙氨酸氨基转移酶、草酰乙酸氨基转移酶、HBeAg阳性、乙型肝炎病毒DNA水平、治疗时段诸因素中仅性别人选回归方程,提示男性较易发生NA.结论不同治疗时段NA发生率相同,阳性率随治疗时间延长升高;男性发生率高于女性.Objective To investigate the generation of neutralizing anti-interferon-alpha antibodies (NA) in patients withchronic hepatitis B in the course of interferon-alpha treatment, and analyze the factors influencing the production of theantibodies. Methods A total of 181 patients with histologically confirmed chronic hepatitis B were enrolled in this study.Recombinant interferon-alpha 1b (rIFN-alpha 1b) was given subcutaneously 3 times a week (5 MU once) in a treatmentcourse lasting for 6 to 37 months (median 10.0 months). In each case, serum NA was detected with antiviral neutralizationbioassay, HBeAg with enzyme-linked immunoassay (EIA) and hepatitis B virus DNA with fluorescent quantitative PCR every 1 to 3 months starting from 3 months after the initiation of the treatment. Results Of the 181 patients, 61 were positive for NAduring the treatment course, resulting in an overall NA occurrence rate of 33.7%. The overall incidence rate, as well as theoverall prevalence rate, was significantly higher in male than in female patients (39.1% vs20.8%, χ2=5.622, P=0.018), and nocorrelations of NA generation was observed with age, pretreatment serum ALT level, serum HBeAg, serum HBV DNA level,liver histological findings or treatment course. Binary logistic regression analysis showed that the only factor in relation withNA production was gender. The prevalence rates of NA varied significantly with the treatment courses ( χ2=98.051, P=0.000).Bivariate correlation analysis showed that the prevalence rate of NA, but not the incidence of NA, was strongly related withthe treatment course (r=0.855, P<0.001). Conclusions In chronic hepatitis B patients treated with rIFN-alpha 1b, theprevalence rate of NA, instead of the incidence of NA, is significantly related to the treatment course. NA was more likely todevelop in male patients to contribute to their poorer antiviral response in comparison with the female patients.

关 键 词：重组α-干扰素 药物治疗 慢性乙型肝炎 抗体 影响因素 

分 类 号：R512.6[医药卫生—内科学]