HBeAg阳性慢性乙型肝炎患者替比夫定相关耐药的临床特点

肝脏 ›› 2018, Vol. 23 ›› Issue (7): 583-586.

HBeAg阳性慢性乙型肝炎患者替比夫定相关耐药的临床特点

金坤, 刘秋霞, 王磊

230001 合肥中国科学技术大学第一附属医院安徽省立医院感染病科(金坤);山东大学第二医院感染/肝病科(刘秋霞,王磊)

收稿日期:2018-03-13 发布日期:2020-04-28
通讯作者: 王磊,Email:wlcrb@sdu.edu.cn
基金资助:
艾滋病和病毒性肝炎等重大传染病防治和“十二五”国家科技重大专项“山东省乙型病毒性肝炎防治综合示范区规模化现场流行病学和干预研究”项目(2013ZX10004902)之子课题——乙肝感染者队列随访和治疗研究。

Clinical characteristics of HBeAg-positive chronic hepatitis B patients developed telbivudine resistance

JIN Kun, LIU Qiu-xia, WANG Lei

Department of infectious diseases, Anhui Provincial Hospital, The First Affiliated Hospital of University of Science and Technology of China, Hefei 230001, China; Department of Infectious Diseases/Hepatology, Second Hospital of Shandong University, Jinan 250033, China

Received:2018-03-13 Published:2020-04-28
Contact: WANG Lei,Email:wlcrb@sdu.edu.cn

摘要/Abstract

摘要： 目的探究HBeAg阳性慢性乙型肝炎(CHB)患者替比夫定治疗导致耐药变异的临床特点。方法对62例接受单一替比夫定抗病毒治疗出现相关耐药的HBeAg阳性CHB患者的抗病毒治疗基线、治疗过程和发生病毒学突破时的资料进行分析,探究替比夫定耐药突变的临床特点。结果替比夫定耐药患者病毒学突破的中位时间为78周,其血清HBV DNA、ALT水平在发生病毒学突破时与基线水平相比,差异有统计学意义;单一位点耐药突变和多位点耐药突变血清HBV DNA水平在发生病毒学突破时相比,差异有统计学意义(u=315.50,P=0.03);检测到8个耐药突变位点、11种组合模式,均含有M204I位点突变。替比夫定耐药组较对照组,年龄、性别、HBeAg、ALT基线水平,差异有统计学意义;替比夫定耐药组12周、24周的HBV DNA阴转率、HBeAg阴转率、HBeAg转换率换均低于对照组患者,差异有统计学意义。结论高龄、男性、HBeAg、ALT基线水平低患者易出现替比夫定耐药;早期实现病毒学转阴及血清学转阴、转换的患者不易耐药。

关键词: 慢性乙型肝炎, 替比夫定, 抗病毒治疗, 耐药突变

Abstract: Objective To investigate clinical characteristics of hepatitis B e antigen (HBeAg) -positive chronic hepatitis B (CHB) patients developed telbivudine resistance. Methods Clinical data of HBeAg-positive CHB patients receiving telbivudine monotherapy at baseline, during treatment and at virological breakthrough was analyzed for investigating clinical characteristics of telbivudine resistance. Results The median time of virological breakthrough occurrence in patients developed telbivudine resistance was 78 weeks. Levels of serum hepatitis B virus (HBV) DNA and alanine aminotransferase (ALT) were significantly lower in patients at virological breakthrough than that at baseline. There was a significant difference in HBV DNA levels between patients with single-site and multiple-site drug resistance mutations when virological breakthrough occurred (u=315.50, P=0.03). Eight drug resistance mutation sites and 11 combination patterns were detected, all containing M204I site mutation. Between telbivudine-resistant group and control group, there were statistically significant differences in age, gender, baseline levels of HBeAg and ALT. Rates of HBV DNA undetectable, HBeAg loss and HBeAg seroconversion in telbivudine-resistant group were significantly lower than those in control group at week 12 and week 24, respectively. Conclusion Patients of older age, male gender, lower baseline levels of HBeAg and ALT were predisposed to develop telbivudine resistance. However, patients who achieved virological and serological response in the early stages are unlikely to develop telbivudine resistance.

Key words: Chronic hepatitis B, Telbivudine, Antiviral therpay, Drug resistance mutation

金坤, 刘秋霞, 王磊. HBeAg阳性慢性乙型肝炎患者替比夫定相关耐药的临床特点[J]. 肝脏, 2018, 23(7): 583-586.

JIN Kun, LIU Qiu-xia, WANG Lei. Clinical characteristics of HBeAg-positive chronic hepatitis B patients developed telbivudine resistance[J]. Chinese Hepatolgy, 2018, 23(7): 583-586.

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