摘要
目的 探讨经核苷（酸）类似物（NA）治疗并获得病毒学应答,且HBeAg仍为阳性的CHB患者对聚乙二醇干扰素-α-2a（peg-IFN-α-2a）治疗的效果及相关因素.方法 HBeAg阳性CHB并经NA只获得维持病毒学应答,于2008年10月至2013年4月转为peg-IFN-α-2a治疗的患者.peg-IFN-α-2a 180 μg皮下注射,每周1次.所有患者采用个性化疗程,对peg IFN-α-2a治疗期间HBsAg和（或）HBeAg持续下降者则继续治疗.患者入组和治疗前检测血清HBV DNA载量、HBV血清学标志物、外周血中性粒细胞和血小板计数、肝脏和肾脏功能指标.peg-IFN-α-2a治疗期间每3个月检测血清HBV DNA载量,HBV血清学标志物.peg-IFN-α-2a治疗结束时,以HBsAg消失或血清转换、HBsAg＜10 IU/mL为主要疗效评价指标;以HBeAg血清学转换、病毒学应答为次要疗效评价指标.每1～3个月监测外周血中性粒细胞和血小板计数,肝脏、肾脏和甲状腺功能.组间差异采用卡方检验,相关因素分析采用Logistic回归分析.结果 共入组81例患者,NA治疗中位时间38.6（25.7～102.9）周;peg-IFN-α-2a治疗中位时间82.0（52.9～109.2）周.在80例治疗结束的患者中,13.8％（11例）患者获得HBsAg消失,12.5％（10例）患者达到HBsAg＜10 IU/mL,23.8％（19例）患者获得HBeAg血清学转换.HBeAg消失患者的peg-IFN-α-2a治疗时间长于HBeAg未消失患者,两组比较差异有统计学意义（x^2 =3.809,P=0.000）.HBsAg消失患者基线水平低于HBsAg未消失患者,两组比较差异有统计学意义（x^2 =3.910,P=0.000）.基线HBsAg＜1 500 IU/mL患者预测治疗结束时HBsAg＜ 10 IU/mL（包括HBsAg消失）的曲线下面积（AUC）为0.784 9,敏感度和特异度为61.9％和86.7％;阳性预测值和阴性预测值为61.9％和86.7％.结论 peg-IFN-α-2a治疗可使经NA治疗获得病毒学应答的HBeAg阳性CHB的患者获得更高的免疫控制,基线HBsAg水平＜1 500 IU/mL可预测peg-IFN-α-2a的疗效.
Objective To investigate the efficacy and the correlation factors of peginterferon-α-2a （peg-IFN-α-2a） treatment in hepatitis B e antigen （HBeAg） positive chronic hepatitis B （CHB） patients who achieved viral response but still was HBeAg positive on nucleos （t）ide analogue （NA） therapy.Methods HBeAg-positive CHB patients who maintained viral response but failed to achieve HBeAg loss on NA treatment were switched to peg IFN-α-2a ther apy.peg-IFN-α-2a 180 μg was administered subcutaneously once weekly.All patients were treated with personalized duration.Patients who achieved sustained decrease of hepatitis B surface antigen （HBsAg） and/or HBeAg during peg-IFN-α-2a administration continued the treatment.Serum level of hepatitis B virus （HBV） DNA,HBV markers,peripheral polymorphonuclear leukocyte and platelet counts,liver and renal functions were measured at enrollment and before treatment.Serum HBV DNA load,HBsAg,anti HBs,HBeAg and anti HBe were detected before and every 3 months during peg-IFN-α-2a treatment.HBsAg loss or seroconversion and HBsAg〈 10 IU/mL at the end of treatment were considered as primary efficacy of response to the treatment.Secondary efficacy was defined as HBeAg seroconversion and virological response.Peripheral polymorphonuclear leukocyte and platelet counts,liver and renal functions and thyroid function were tested every 1-3 months.Inter-group differences were compared using Chi-square test.Correlation factors were analyzed using Logistic regression.Results Eighty one patients,with a median of 38.6 （25.7-102.9） weeks of NA treatment and 82.0 （52.9-109.2） weeks of peg-IFN-α-2a treatment,were consecutively enrolled.Of 80 cases who ended peg-IFN-α-2a treatment,13.8% （11/80） of patients achieved HBsAg loss and 12.5% of patients achieved HBsAg〈10 IU/mL at the end of peg-IFN-α-2a therapy.HBeAg seroconversion occurred in 23.8 % of patients.The duration of peg-IFN-α-2a treatment was significantly longer in patients who achieve HBeAg loss than those who did not （x^2 =3.809,P =0.000）.Baseline HBsAg level was significantly lower in patients who achieved HBsAg loss than those who did not （x^2 =3.910,P=0.000）.Area under curves （AUC） for baseline HBsAg〈1 500 IU/mL in predicting HBsAg〈 10 IU/mL （including HBsAg loss） at the end of peg-IFN-α-2a treatment was 0.784 9,with a sensitivity of 61.9 %,specificity of 86.7 %,positive predictive value of 61.9 % and negative predictive value of 86.7 %.Conclusion HBeAg-positive CHB patients who maintained viral response on NA treatment can achieve better immune control after switching to peg-IFN-α-2a treatment.The baseline HBsAg〈 1 500 IU/mL could effectively predict the response of peg-IFN α 2a therapy.
出处
《中华传染病杂志》
CAS
CSCD
北大核心
2014年第5期274-279,共6页
Chinese Journal of Infectious Diseases
