【摘要】 目的观察PEG-IFNα-2a单药治疗HBeAg阳性慢性乙型肝炎(CHB)患者48周血清学应答不佳序贯应用替诺福韦酯(TDF)治疗24周的疗效。方法纳入2015年6月-2016年2月就诊于上海市公共卫生临床中心,经PEG-IFNα-2a 180μg/周治疗48周HBeAg未发生血清学转换的CHB患者共21例。其中11例患者加用TDF 300 mg/d,12周后停用PEG-IFNα-2a,继续予TDF单药治疗12周;10例患者序贯阿德福韦酯(ADV)10 mg/d单药治疗24周。治疗12、24周时检测HBV DNA,肝、肾功能,HBV血清学标志物等指标,对比两组疗效。两组计量资料比较,满足正态分布的组间比较采用独立样本t检验,组内比较采用配对t检验;不满足正态分布的采用Mann-Whithey U检验。计数资料比较采用Fisher确切概率法。结果治疗12、24周时,两组患者的HBs Ag、HBeAg水平差异无统计学意义(P值均>0.05)。治疗24周时,TDF组患者HBeAg转换率(18.2%,2/11)与ADV组(10.0%,1/10)比较差异无统计学意义(P>0.05);TDF组患者治疗12、24周时HBeAg分别为(1.75±0.59)log10S/CO、(1.61±0.70)log10S/CO,较基线[(1.86±0.58)log10S/CO]明显下降,差异均有统计学意义(P值分别为0.017、0.027);治疗24周时TDF组患者ALT水平低于ADV组,差异有统计学意义[21.0(15.0~27.0)U/L vs 33.0(21.5~63.5)U/L;U=-2.616,P=0.046]。两组患者e GFR水平在治疗12、24周差异均无统计学意义(P值均>0.05)。结论对于PEG-IFNα-2a单药治疗48周HBeAg血清学应答不佳的CHB患者,加用TDF 12周后再单用TDF 12周较直接序贯ADV治疗,短期内更有助于降低血清ALT和HBeAg水平。更多还原

【Abstract】 Objective To investigate the clinical effect of 24- week tenofovir disoproxil fumarate( TDF) sequential therapy in HBeAg- positive chronic hepatitis B( CHB) patients with suboptimal serological response to 48- week pegylated interferon- α- 2a( Peg- IFN- α- 2a) monotherapy. Methods A total of 21 patients who did not achieve HBeAg seroconversion after the 48- week Peg- IFN- α- 2a monotherapy at a dose of 180 μg / week were enrolled. Among these patients,11 were given TDF 300 mg / d in addition,the withdrawal of Peg- IFN- α- 2a after 12 weeks,and TDF monotherapy for 12 weeks; 10 were given sequential adefovir dipivoxil( ADV) monotherapy at a dose of 10 mg / d for 24 weeks. The indicators including HBV DNA,liver and renal function,and HBV serological markers were measured at weeks 12 and 24 of treatment,and the clinical outcome was compared between the two groups. The independent samples t- test was used for comparison of normally distributed continuous data between groups and the paired t- test was used for comparison of normally distributed continuous data within one group; the Mann- Whitney U test was used for comparison of non- normally distributed continuous data between groups. The Fisher’s exact test was used for comparison of categorical data. Results At weeks 12 and 24 of treatment,there were no significant differences in HBs Ag and HBeAg levels between groups( both P > 0. 05). At week 24 of treatment,there was no significant difference in HBeAg seroconversion rate between the TDF group and the ADV group [18. 2%( 2 /11) vs 10. 0%( 1 /10),P > 0. 05]. At weeks 12 and 24 of treatment,the TDF group had significant reductions in HBeAg compared with baseline( 1. 75 ± 0. 59 log10 S / CO、1. 61 ± 0. 70 log10 S / CO vs1. 86 ± 0. 58 log10 S / CO,P = 0. 017 and 0. 027). At week 24 of treatment,the TDF group had a significantly lower alanine aminotransferase( ALT) level than the ADV group[21. 0( 15.0-27.0) U/L vs 33. 0( 21. 5-63. 5) U/L,P =0.046]. There were no significant differences in estimated glomerular filtration rate at weeks 12 and 24 of treatment between the two groups( both P > 0. 05). Conclusion As for CHB patients with suboptimal serological response to 48- week Peg- IFN- α- 2a monotherapy,addition of TDF for 12 weeks and then TDF monotherapy for 12 weeks helps to achieve greater reductions in serum ALT and HBeA g levels compared with sequential ADV therapy.更多还原