重组人干扰素α-1b单药及联合治疗e抗原阳性慢性乙型肝炎的疗效

A multicenter study of the effectiveness of interferon alpha-1b （Hapgen） in treating HBeAg positive chronic hepatitis B patients

目的 观察重组人干扰素（IFN）α-1b和重组人IFN α-1b联合拉米夫定（LAM）治疗HBeAg阳性慢性乙型肝炎患者的疗效,并分析影响疗效的因素.方法收集HBeAg阳性慢性乙型肝炎患者111例,其中49例为单药治疗组,给予重组人IFN α-1b治疗（50μg/次,隔日1次,肌肉注射）,62例为联合治疗组,给予重组人IFN α-1b（50μg/次,隔日1次,肌肉注射）加LAM（100 mg/d,口服）联合治疗,疗程为6～12个月或＞12个月.在治疗前、治疗后3、6、9、12、18个月及治疗结束时比较两组患者的HBV DNA低于检测下限率、HBeAg及HBsAg血清转换率.同时检测LAM的耐药变异情况.采用t检验和x2检验进行统计分析.结果 （1）治疗3、6、9、12、18个月后,单药治疗组HBeAg血清学转换率分别为6.1%、8.2%、14.3%、28.6%、36.7%,联合治疗组HBeAg血清学转换率分别为1.6%、8.1%、14.5%、29.0%、38.7%,两组比较,x2值分别为1.602、0.000、0.001、0.003、1.500,P值均＞0.05,差异均无统计学意义;（2）治疗3、6、9、12、18个月后,单药治疗组HBV DNA低于检测下限率分别为0、8.2、36.7%、53.1%、57.1%,联合治疗组HBV DNA低于检测下限率分别为30.7%、66.1%、79.0%、83.9%、88.7%,两组比较,x2值分别为25.205、38.150、20.465、12.073、14.459,P值均＜0.05,差异有统计学意义;（3）单药治疗组,男性患者组和女性患者组HBeAg血清学转换率分别为34.5%、40.0%两组比较,差异无统计学意义.年龄≥40岁和＜40岁的患者的HBeAg血清转换率分别为50.0%、34.9%,两组比较,差异无统计学意义.HBV DNA≥6 log10拷贝/ml和HBV DNA＜6 log10拷贝/ml的患者HBeAg血清转换率分别为52.4%、25.0%两组比较,x2=3.871,P＜0.05,差异有统计学意义.结论 （1）适当延长疗程有利于HBeAg阳性慢性乙型肝炎患者HBeAg血清学的转换;（2）联合治疗组HBV DNA低于检测下限率高于单药治疗组;（3）单药治疗组中,高HBVDNA载量患者HBeAg血清转换率比低HBV DNA载量患者低.

Objective To compare the efficacy and safety of interferon α -1b and interferon α-1b combined with lamivudine in the treatment of HBeAg positive chronic hepatitis B （CHB）, to analyze the impact of variable factors on the efficacy, and to investigate the individualized anti-viral regimen for CHB patients. Methods 111 CHB patients were enrolled and randomly divided into two groups. Group A：patients received interferon α -1b （49 patients, 50 μg I. M., qod. ）, Group B： interferon α -1b （idem）combined with lamivudine for 6-12 months or longer（62 patients, 100 mg, P. O., q. d. ）. Results （1） The HBeAg seroconversion rates of treatment by 12 and 18 months were 28.6% and 36.7% in group A, 29.0% and 38.7% in group B, respectively, no significant difference found between the two groups at the end of treatment（ x2 = 0.003, P 〉 0.05; x2 = 1.500, P 〉 0.05）. （2） The HBV DNA undetectable rates of treatment by 6months, 12 months and 18 months were 8.2%, 53.1% and 57.1% in group A,66.1%, 83.9% and 88.7% in group B, respectively, still no significant difference existed between the two groups （ x2 = 38.150, P 〈 0.05;x2 = 12.073, P 〈 0.05, x2 = 14.459, P 〈 0.05）. （3） In group A, the HBeAg seroconversion rates for male and female patients were 34.5% and 40.0% respectively, no significant difference found between. As regard ages the rates were 34.9% and 50.0% for patients younger or more than 40 years of age, no significant difference existed between. The HBeAg seroconversion rate was higher in patients with lower baseline serum HBV DNA loads （〈 6 log10copies/ml）. （4） The rates of patients with fever and blood abnormality were 36.7% and 34.7% in group A, 32.3% and 27.4% in group B, respectively. The total incidences of adverse events were similar between group A and B （ x2 = 0.244, P 〉 0.05; x2 = 0.682, P 〉 0.05）. （5） The ratio of drug resistance in group B was only 1.6%. Conclusion The adverse events of interferon α -1b treatment for CHB are low and mild. The HBeAg seroconversion rate persistently raises with the extension of interferon α -1b treatment course. The HBV DNA undetectable rate of interferon α -1b combined with lamivudine is significantly higher than that of interferon α -1b and the drug resistance of lamlvudine can be reduced obviously by combination therapy.