替诺福韦治疗其他核苷（酸）类药物耐药或应答不佳慢性乙型肝炎48周疗效分析  

Efficacy of 48-week treatment of tenofovir disoproxil fumarate for chronic hepatitis B patients with resistance or suboptimal response to other nucleoside analogues

作　　者：袁国盛 杨年欢[2] 王欣欣[1] 姚红卫[3] 于文轩[1] 熊玲[1] 成姚 张浩[1] 王俊洁[1] 周福元[1] 周元平[1] 

机构地区：[1] 南方医科大学南方医院感染内科,广州510515 [2] 南方医科大学第一临床医学院 [3] 南方医科大学南方医院药剂科,广州510515

出　　处：《中华临床感染病杂志》2015年第1期4-8,共5页Chinese Journal of Clinical Infectious Diseases

基　　金：国家自然科学基金（81470856）;中国肝炎防治基金会项目（XJS20120601）

摘　　要：目的 探讨替诺福韦（TDF）挽救性治疗其他核苷（酸）类药物（NAs）治疗后耐药或应答不佳慢性乙型肝炎（CHB）患者的疗效和安全性.方法 回顾性分析2012年5月至2014年7月南方医科大学南方医院收治的经NAs治疗耐药（18例）和应答不佳（31例）的CHB患者的资料.所有患者均使用替诺福韦治疗,方法为300 mg,1次/d,疗程为48周.所有患者均在服药前及治疗后第4、12、24、48周测定生物化学和病毒学指标.采用重复测量方差分析比较不同时间点各项指标的差异,同时采用两独立样本t检验、Mann-Whitney U检验、x2检验和Fisher检验比较耐药组和应答不佳组在HBV DNA下降幅度、HBV DNA转阴率和ALT复常率等方面的差异.结果 49例CHB患者的HBVDNA水平在治疗第4、12、24和48周累积下降幅度分别为（0.83±0.88）、（2.02±1.80）、（2.74 ±2.11）和（3.65±2.23） lg U/mL,较基线水平均有明显下降（F =30.18,P＜0.01）.第48周HBV DNA累积转阴率为87.8％ （43/49）,ALT复常率为67.6％ （23/34）.耐药组与应答不佳组HBV DNA转阴中位时间分别为12和4周（x2=0.03,P＞0.05）,ALT复常中位时间分别为24和12周（x2=2.89,P＞0.05）.未记录到明显不良反应.结论 对于其他NAs治疗后耐药或应答不佳的CHB患者,TDF仍具有强效抗病毒作用,且无明显不良反应.Objective To evaluate the efficacy and safety of tenofovir disoproxil fumarate （TDF）therapy for chronic hepatitis B （CHB） patients with resistance or suboptimal response to other nucleoside analogues （NAs）.Methods Data of 49 CHB patients including 18 with resistance and 31 with suboptimal response to other NAs were collected from Nanfang Hospital,Southern Medical University during May 2012 and July 2014.All patients received TDF 300 mg/d for 48 weeks.Biochemical and virological indexes at baseline,week 4,week 12,week 24 and week 48 during treatment were collected for evaluation.The differences of investigated indexes among all time points were studied by repeated measures analysis of variance,while the differences in the decrease of HBV DNA loads,HBV DNA negative conversion rates and serum alanine aminotransferase （ALT） normalization rates between resistant group and suboptimal response group were evaluated by independent samples t test,Mann-Whitney U test,chi-square test and Fisher test.Results The cumulative decrease of HBV DNA load at week 4,week 12,week 24 and week 48 after treatment were （0.83 ± 0.88）,（2.02 ± 1.80）,（2.74 ± 2.11） and （3.65 ± 2.23） lg U/mL,which was statistically significant compared with the baseline value （F =30.18,P 〈 0.01）.The cumulative HBV DNA negative conversion rate and ALT normalization rate at week 48 was 87.8% （43/49） and 67.6% （23/34）,respectively.The median time to achieve HBV DNA negative conversion were 12 weeks in resistant group and 4 weeks in suboptimal response group （x2 =0.03,P 〉 0.05）,and the median time to achieve normal ALT level were 24 weeks in resistant group and 12 weeks in suboptimal group （x2 =2.89,P 〉 0.05）.No significant adverse reaction was recorded.Conclusion TDF is effective and safe for CHB patients who are resistant or with suboptimal response to other NAs.

关 键 词：肝炎 乙型 慢性 抗药性 替诺福韦 

分 类 号：R512.62[医药卫生—内科学]