摘要目的 探讨恩替卡韦经治后低HBsAg水平慢性乙型肝炎患者(CHB)联合聚乙二醇干扰素α-2b(Peg IFNα-2b)治疗后的临床疗效.方法 选取2014年1月至2016年1月浦江县人民医院和浙江大学医学院附属第一医院门诊治疗的69例恩替卡韦经治的CHB患者作为研究对象,所有患者HBsAg＜2 000 IU/mL且HBV DNA＜100 IU/mL,将患者随机分为Peg IFNα-2b(1.5 μg/kg,皮下注射,1次/周)联合恩替卡韦(0.5 mg/d)治疗组39例(联合治疗组)与恩替卡韦(0.5 mg/d)继续治疗组30例(恩替卡韦组).观察两组患者血清HBsAg定量、HBsAg阴转、HBeAg血清学转化和丙氨酸转氨酶(ALT)的基线以及治疗后12、24、48、72及96周时的水平.结果 联合治疗组HBsAg水平随着治疗时间的延长逐渐下降,治疗24周时与恩替卡韦组相比,差异具有统计学意义( Z＝－2.566, P＜0.05),在治疗48、72和96周时HBsAg下降幅度明显高于恩替卡韦组( Z＝－3.499、－3.825和－3.864,P＜0.01).联合治疗组在治疗24周出现HBsAg阴转,阴转率为7.70%(3/39),在第96周HBsAg阴转率为28.20%(11/39),恩替卡韦组在治疗96 周才出现HBsAg 阴转,阴转率为3.30%(1/30),联合治疗组在48、72和96周HBsAg阴转率均高于恩替卡韦组组( P＜0.05或＜0.01).联合治疗组临床治愈11例,临床显效11例,临床有效17例;恩替卡韦组临床治愈1例,临床显效1例,临床有效28例,联合治疗组疗效优于恩替卡韦组(χ2＝18.496,P＜0.01).联合治疗组HBeAg在治疗12周阴转率为30.00%(6/20),在治疗96周时为65.00%(13/20),恩替卡韦组在治疗48周出现2例HBeAg阴转(2/18),在治疗96 周4例出现HBeAg阴转(4/18),两组在治疗12、24、72 和96 周HBeAg阴转率差异均具有统计学意义(P＜0.05或＜0.01).联合治疗组在12周、24周时ALT均有升高,与恩替卡韦组差异具有统计学意义(Z＝－1.236和－2.658,P＜0.05),在治疗48周后ALT水平逐渐下降,与恩替卡韦组无统计学差异.预测因素分析提示恩替卡韦联合Peg IFNα-2b治疗、基线HBeAg水平低能提高HBsAg阴转率(P值均＜0.01).结论 恩替卡韦经治后HBsAg低水平的CHB患者联合Peg IFNα-2b治疗能有效提高HBeAg阴转率及临床治愈率.

abstractsObjective To analyze the efficacy of entecavir (ETV) combined with Peg IFNα-2b in chronic hepatitis B ( CHB) patients with low levels HBsAg following initial ETV treatment.Methods Sixty-nine CHB outpatients achieving serum HBsAg ＜2 000 IU/mL and HBV DNA＜100 IU/mL following initial ETV treatment in Pujiang People's Hospital and the First Affiliated Hospital of Zhejiang University School of Medicine from January 2014 to January 2016 were enrolled.Patients were randomly assigned in two groups: 39 patients in combination group received ETV (0.5 mg/d ) and Peg IFNα-2b (1.5 μg· kg－1· week －1, hypodermic injection), and 30 patients in ETV group received ETV (0.5 mg/d) alone.Serum HBsAg quantification, negative conversion rate of HBsAg and HBeAg , and levels of aminotransferase (ALT) were measured at baseline , 12th, 24th, 48th, 72th and 96th week after treatment.Results The levels of HBsAg in the combination group decreased gradually with the prolongation of therapy , which were lower than those in ETV group 24 week after treatment (Z＝－2.566,P＜0.05),and at 48th, 72th and 96th week (Z＝－3.499,－3.825 and －3.864,P＜0.01).Clearance of HBsAg appeared in the combination group at 24th week,the clearance rates were 7.70%(3/39) and 28.20%(11/39) at 24th and 96th week, respectively;while the clearance of HBsAg occurred in ETV group at 96th week, the clearance rate was only 3.30%(1/30).The negative conversion rates of HBsAg in combination group were higher than those in ETV group at 48th,72th and 96th week (P＜0.05 or＜0.01).In the combination group, there were 11 cases of clinical cure , 11 cases of clinical efficacy and 17 cases of clinical effectiveness , while there were 1, 1 and 28 cases in ETV group,respectively.The treatment effect of the combination group was better than that of ETV group(χ2＝18.496,P＜0.01).Serological conversion rates of HBeAg were 30.00%(6/20) and 65.00%(13/20) in combination group at 12th and 96th week, while those were 11.11%(2/18) and 22.22%(4/18) in ETV group at 48th and 96th week.There were significant differences in the HBeAg serological conversion rates at 12th, 24th, 72th and 96th week between two groups (P＜0.05 or ＜0.01). The levels of ALT in combination group increased at 12th and 24th week, which had significant difference compared with ETV group (Z＝－1.236 and －2.658,P＜0.05), and the ALT levels gradually declined 48 week after treatment in combination group and there were no statistical differences between two groups at other time points.The ETV combined with Peg IFNα-2b and low baseline HBeAg levels were associated with the clearance rate of HBsAg (both P＜0.01).Conclusions CHB patients with low HBsAg levels following initial ETV monotherapy can achieve high negative conversion rate of HBeAg and HBsAg with the combination treatment of ETV and Peg IFN α-2b.