核苷类药物初治应答不佳的慢性乙型肝炎患者换用替诺福韦的疗效和安全性研究

肝脏 ›› 2022, Vol. 27 ›› Issue (12): 1300-1304.

核苷类药物初治应答不佳的慢性乙型肝炎患者换用替诺福韦的疗效和安全性研究

陈彤彤, 范蕊芳, 杨雅萱, 张烨琼, 许文雄, 彭亮, 李杨湄

510630 广州中山大学附属第三医院(陈彤彤,范蕊芳,杨雅萱,张烨琼,许文雄,彭亮,李杨湄);570311海南省人民医院感染科(陈彤彤)

收稿日期:2022-01-10 发布日期:2023-01-30
通讯作者: 李杨湄,Email:spice205@163.com
作者简介:共同第一作者:范蕊芳
基金资助:
国家自然科学基金面上项目(82070611和81873572);中山大学5010临床研究项目(2020007和218009)

A study on the efficacy and safety of switching initial poor-responsive nucleoside analogues to Tenofovir treatment in chronic hepatitis B patients

CHEN Tong-tong^1,2, FAN Rui-fang¹, YANG Ya-xuan¹, ZHANG Ye-qiong¹, XU Wen-xiong¹, PENG Liang¹, LI Yang-mei¹

1. The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, China;
2. Hainan General Hospital,Haikou 570311, China

Received:2022-01-10 Published:2023-01-30
Contact: LI Yang-mei, Email:spice205@163.com

摘要/Abstract

摘要： 目的观察核苷类药物(nucleoside analogues, NAs)治疗后病毒学应答不佳的慢性乙型肝炎(chronic hepatitis B, CHB)患者换用替诺福韦(Tenofovir, TDF)的疗效和安全性。方法本研究经筛选后纳入108例患者,分为恩替卡韦(Entecavir, ETV)治疗后继续ETV治疗组(ETV to ETV组)(32例)、ETV治疗后换用TDF组(ETV to TDF组)(30例)和非ETV的NAs治疗后换用TDF组(Non-ETV to TDF组)(46例)。观察各组在基线前后各个随访点HBV DNA累计不可检测率、HBV DNA定量等病毒学指标,丙氨酸氨基转移酶、血清肌酐等生化指标的差异。结果 ETV to TDF组与ETV to ETV组相比,第24周HBV DNA定量对数为2.0(2.0~2.0)IU/mL vs. 2.0(2.0~2.5)IU/mL(P=0.034);第24周HBV DNA累计不可检测率为83.3% vs. 56.3%,差异有统计学意义(χ²=5.34, P=0.021),ETV to TDF组明显优于ETV to ETV组;两组之间的总体的HBV DNA不可检测耗时分布的差异不具有统计学意义(χ²=2.366, P=0.124),但HBV DNA不可检测耗时平均值两组分别为(24.8±3.57)和(36.4±5.35)周。ETV to TDF组与Non-ETV to TDF组相比,24和48周的HBV DNA累计不可检测率分别为83.3% vs.82.8%(P=0.935)和90% vs.93.5%(P=0.675),差异均无统计学意义。换药前ETV疗程在48~96周内在换用TDF后HBV DNA转阴时间之间差异无统计学意义(P=0.270)。所有随访患者均未发生病毒学突破。所有随访患者均未发生严重的不良反应,如横纹肌溶解等。结论换用TDF治疗其他核苷类药物初治后病毒学应答不佳的患者是一种疗效好,安全性高的治疗方法。换用TDF治疗可能在一定程度上比继续ETV治疗更快促进ETV应答不佳患者的HBV DNA阴转。ETV疗程在48至96周内可能并不会影响后续换用TDF疗效。

关键词: 慢性乙型肝炎, 替诺福韦, 恩替卡韦, 应答不佳

Abstract: Objective To observe the efficacy and safety of switching poor virological responsive nucleoside analogues (NAs) to Tenofovir (TDF) treatment in chronic hepatitis B (CHB) patients.Methods One hundred and eight CHB patients were enrolled after screening. They were divided into the following three groups based on their drug switch regimes: ETV to ETV group (n=32), ETV to TDF group (n=30) and NON-ETV to TDF group (n=46). The differences of cumulative HBV DNA undetectable rate, HBV DNA quantification load and other viral indicators, alanine aminotransferase, serum creatinine and other biochemical parameters in each group at baseline and at each follow-up point were observed and compared.Results The quantitative logarithms of HBV DNA at week 24 were 2.0 (2.0-2.0) IU/mL in the ETV-to-TDF group compared with that of 2.0 (2.0-2.50) IU/mL in the ETV-to-ETV group (P=0.034). At week 24, the cumulative undetectable rate of HBV DNA in ETV to TDF group was 83.3%, which was significantly higher than that of 56.3% in ETV to ETV group (χ²=5.34, P=0.021). There was no significant difference in the duration of HBV DNA undetectable time between the two groups(24.8±3.57 vs. 36.4±5.35 weeks, P=0.124). The cumulative undetectable rates of HBV DNA at 24 and 48 weeks of the ETV to TDF group compared with those of the non-ETV to TDF group were 83.3% vs. 82.8% (P=0.935) and 90% vs. 93.5% (P=0.675), respectively, and the differences were not statistically significant. There was no statistical correlation between the course of ETV treatment within 48 to 96 weeks and the HBV DNA negative conversion time after switching to TDF (P=0.270). No virological breakthrough occurred in any of the patients. None of the patients had serious adverse reactions such as rhabdomyolysis.Conclusion TDF is an effective and safety treatment for patients with poor virological response to initial treatment with other nucleoside drugs. Switching to TDF therapy rather than continuing ETV therapy may promote HBV DNA negative conversion in patients with poor responsiveness to ETV treatment. The course of ETV treatment within 48 to 96 weeks may not affect the efficacy of switching to TDF treatment thereafter.

Key words: Chronic hepatitis B, Tenofovir, Entecavir, Poor responsiveness

陈彤彤, 范蕊芳, 杨雅萱, 张烨琼, 许文雄, 彭亮, 李杨湄. 核苷类药物初治应答不佳的慢性乙型肝炎患者换用替诺福韦的疗效和安全性研究[J]. 肝脏, 2022, 27(12): 1300-1304.

CHEN Tong-tong, FAN Rui-fang, YANG Ya-xuan, ZHANG Ye-qiong, XU Wen-xiong, PENG Liang, LI Yang-mei. A study on the efficacy and safety of switching initial poor-responsive nucleoside analogues to Tenofovir treatment in chronic hepatitis B patients[J]. Chinese Hepatolgy, 2022, 27(12): 1300-1304.

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