HBeAg阳性慢性乙型肝炎核苷(酸)类似物序贯干扰素治疗疗效的相关因素研究

Factors associated with efficacy of inucleoside analogues on sequential interferon therapy in HBeAg positive chronic hepatitis B patients

目的研究HBeAg阳性慢性乙型肝炎(chronic hepatitis B,CHB)患者核苷(酸)类似物[(nucleos(t)ide analogs,NA]序贯干扰素治疗疗效的影响因素。方法NA治疗的HBeAg阳性CHB向PEG-IFNα-2a转换(序贯治疗),二者联合应用3个月后单独应用PEG-IFNα-2a治疗,PEG-IFNα-2a 180μg每周1次皮下注射。监测序贯治疗前(基线)及序贯治疗的第12、24、36、48、及72周的HBsAg、HBeAg和HBV DNA含量。结果共有56例HBeAg阳性的CHB患者入组,其中5例(8.9%)获得HBsAg消失/血清学转换,获得组基线HBsAg含量显著低于非获得组(2.750 lg IU/ml vs 3.699 lg IU/ml,t=0.955,P=0.000);序贯治疗的第12、24、36、48周两组HBsAg下降幅度差异均有统计学意义(0.913 vs 0.149,2.847 vs 0.189,4.378 vs 0.248,4.587 vs 0.274,lg IU/ml)(t=-2.950、P=0.040;t=-8.732、P=0.009;t=-8.483、P=0.001;t=-8.214,P=0.003)。11例(19.6%)获得HBeAg消失/血清学转换,获得组基线HBeAg含量低于非获得患者(1.217 lgS/CO vs 1.884 lgS/CO,t=2.061,P=0.044);序贯治疗第24、36、48周两组HBsAg、HBeAg下降幅度差异均有统计学意义(1.330 vs 0.205,2.084 vs 0.258,1.972 vs 0.284,lg IU/ml;1.168 vs 0.455,1.363 vs 0.461,1.177 vs 0.447,lgS/CO)(t=2.238、p=0.049,t=2.619、P=0.025,t=2.278、P=0.048;t=2.273、P=0.043,t=3.415、P=0.001,t=2.271、P=0.049)。结论基线HBsAg、HBeAg以及其早期滴度下降均可预测HBeAg阳性的CHB患者应用核苷(酸)类似物序贯干扰素治疗的HBs(e)Ag消失/血清学转换率。

Objective To study the factors associated with efficacy of nucleos(t)ide analogues with sequential interferon in HBeAg positive chronic hepatitis B(CHB)patients.Method HBeAg positive CHB patients treated with nucleoside analogue(NA)treatment received PEG-IFNα-2a 180μg subcutaneously once weekly.NA was continually used with PEG-IFNα-2a during the first 12 weeks.HBsAg/HBeAg level and HBV DNA load were observed in the sequential pre-treatment(baseline)period,12 th,24 th,36 th,48 th and 72 nd weeks of sequential therapy in all patients.Result Of the 56 HBeAg-positive CHB patients,5(23.1%)achieved HBsAg loss/seroconversion,the baseline HBsAg level in HBsAg loss/seroconversion group was lower than that of the patients in the group that did not achieve HBsAg loss/seroconversion(2.750 lg IU/ml vs.3.699 lg IU/ml,t=0.955,P=0.000);the difference was statistically significant in HBsAg decreased at the 12 th,24 th,36 th,48 th week in the course of sequential therapy(0.913 vs 0.149,2.847 vs 0.189,4.378 vs 0.248,4.587 vs 0.274 lg IU/ml)(t=-2.950,P=0.040;t=-8.732,P=0.009;t=-8.483,P=0.001;t=-8.214,P=0.003);11(19.6%)achieved HBeAg loss/seroconversion,the HBeAg baseline level in HBeAg loss/seroconversion group was lower than the patients in the group that not achieved HBeAg loss/seroconversion(1.217 lgS/CO vs 1.884 lgS/CO,t=2.061,P=0.044);the difference was statistically significant in HBsAg,HBeAg decreased at 24 th,36 th,48 th week in the course of sequential therapy between the two groups(1.330 vs 0.205,2.084 vs 0.258,1.972 vs 0.284,lg IU/ml;1.168 vs 0.455,1.363 vs 0.461,1.177 vs 0.447,lg S/CO)(t=2.238,P=0.049;t=2.619,P=0.025;t=2.278,P=0.048);(t=2.273,P=0.043;t=3.415,P=0.001;t=2.271,P=0.049).Conclusions To HBeAg-positive CHB,lower baseline HBsAg,HBeAg level and HBsAg,HBeAg decreased earlier were could predict easier achievement of HBs(e)Ag loss/seroconversion.