聚乙二醇化干扰素α-2a治疗慢性乙型肝炎的临床研究

Pegylated interferon alpha 2a in treating chronic hepatitis B patients

目的评价聚乙二醇化干扰素(PEG-IFN)α-2a治疗慢性乙型肝炎(CHB)的疗效和安全性。方法72例CHB患者随机分配到治疗组和对照组。治疗组(30例)予PEG-IFNα2a 180μg皮下注射,每周1次,疗程48周。对照组(42例)予普通干扰素500MU,皮下注射,隔日1次,疗程48周,治疗结束后随访48周。结果治疗12周时,治疗组乙型肝炎e抗原(HBeAg)的阴转率达到30%,明显高于对照组,x^2=4．162,P＜0．05,HBeAg定量及乙型肝炎病毒(HBV DNA)定量对数值明显低于治疗前水平,t值分别为2．689、4．080,P＜0．01,而对照组治疗12周时与治疗前相比,差异无统计学意义,t值分别为1．229、1．009,P＞0．05；治疗24周时,治疗组乙型肝炎e抗原(HBeAg)阴转率明显高于对照组,x^2=6．190,P＜0．05,HBeAg定量和HBV DNA定量的对数值均明显低于对照组,t值分别为2．215、2．122,P＜0．05；治疗48周时,治疗组除上述观察指标优于对照组外,HBeAg/抗-HBe血清转换率、丙氨酸氨基转移酶的复常率及完全应答率也明显高于对照组,x^2值分别为5．771、5．617、5．308,P＜0．05；治疗结束后随访48周时,治疗组HBeAg的阴转率、HBeAg定量、HBV DNA定量对数值、HBeAg/抗-HBe血清转换率、丙氨酸氨基转移酶的复常率及完全应答率均明显优于对照组,分别为x^2=11．943、t=3．439、t=6．111、x^2、9．930、x^2=9．522、x^2=7．920,P值均＜0．01,而且保持持续应答,而对照组的应答率则有所下降；治疗组9例患者于治疗前后做2次肝活组织检查,治疗前肝组织中的乙型肝炎表面抗原及核心抗原阳性率分别为88．89%和66．67%,治疗结束时分别为22．22%和33．33%,乙型肝炎表面抗原较治疗前明显减少,x^2=8．001,P＜0．01；治疗前后肝组织的炎症活动度、纤维化程度及胶原表达无明显差异。治疗组有3例出现HBsAg阴转,阴转率为10%,其中2例出现在治疗后32周,1例出现在治疗结束后24周,对照组无一例阴转。PEG-IFNα-2a的不良反应与对照组相似。结论PEG IFNα-2a治疗慢性乙型肝炎能有效地抑制其病毒复制,且能持续应答,治疗48周内安全且耐受性良好。

Objective To evaluate the efficacy and safety of pegylated interferon alpha 2a （PEG-IFN α -2a） in treating patients with chronic hepatitis B. Method Seventy-two patients with chronic hepatitis B were assgned to a PEG-IFN α -2a （experimental） group （n=42） and an interferon α （control） group （n=30） randomly. Each patient in the experimental group received 180 μg PEG-IFN α -2a every week. Each patient in the control group received 500 MU interferon a every day. All the patients were treated for 48 weeks, and then were followed for another 48 weeks with no treatment. Results At the end of the 12th week, the rate of HBeAg negative cases was 30% in the PEG-IFN α -2a group, which was much higher than in the control group （ x^ 2 = 4.162, P 〈 0.05）. The values of HBeAg and the log value of HBV DNA in the PEG-IFN α -2a group were much lower than the values before the treatment （t = 2.689, t = 4.080, P 〈 0.01）, but there was no difference between before and after treatment in the control group （ t = 1.229, t = 1.009, P 〉 0.05）. At the end of the 24th week, the rate of HBeAg negative cases in the PEG-IFN α -2a group was much higher than that in the control group （ x^2 = 6.190, P 〈 0.05）. The value of HBeAg and the log value of HBV DNA in the PEG-IFN α -2a group were much lower than in the control group （t = 2.215, t = 2.122, P 〈 0.05）.At the end of the 48th week, besides the reduction mentioned above, the rate of cases with HBeAg/antiHBe seroconversion and normalization of ALT and complete responsiveness in the PEG-IFN α -2a group were all much higher than those in the control group （ x^ 2 = 5.771, x ^2 = 5.617, x ^2 = 5.308, P 〈 0.05）. At the end of 48 weeks with no treatment, all the parameters mentioned above in the PEG-IFN α-2a group were much better than those in the control group and they remained so, but they were different in the control group （ x^ 2 = 11.943, t = 3.439, t = 6.111, x^ 2 = 9.930, x^ 2 = 9.522, x^ 2 = 7.920, P 〈 0.01）. Nine patients in the PEG-IFN α -2a group had liver biopsies before their treatment and also at the end of their treatment. The expressions of HBsAg and HBcAg were decreased at the end of the treatment. The rate of expression of HBsAg in the liver tissues before the treatment was 88.9% but only 22.2% at the end of the treatment （ x^2 = 8.001, P 〈 0.01）. The rate of expression of HBcAg in the livers before treatment was 66.7% but only 33.3% at the end of the treatment. Before and at the end of the PEG-IFN α -2a treatment, there were no significant changes in the degrees of inflammation and fibrosis and the quantity of collagen in the liver tissues. Three patients in the PEG-IFN α -2a group （10%） were HbsAg negative. Two of them were found so at the end of 32 weeks with treatment and one patient was found at the end of 24 weeks with no treatment, but there were no HBsAg negative patients in the control group. The adverse reactions that occured in the PEG-IFN α -2a and in the control groups were similar. Conclusion PEG-IFN α-2a was effective in inhibiting HBV replication. The effect of PEG-IFN α -2a was lasting. PEG-IFN α-2a was well tolerated during our treatment.