慢性乙型肝炎患者恩替卡韦基因型耐药突变模式及其结果分析

肝脏 ›› 2024, Vol. 29 ›› Issue (12): 1472-1475.

慢性乙型肝炎患者恩替卡韦基因型耐药突变模式及其结果分析

王章云, 王延丽, 何行昌

214000 江苏上海交通大学医学院附属瑞金医院无锡分院感染和肝病科(王章云); 450000 河南郑州大学附属传染病医院感染科(王延丽); 476100 商丘市第一人民医院肝脏科(何行昌)

收稿日期:2024-07-23 出版日期:2024-12-31 发布日期:2025-02-19
通讯作者: 王延丽,Email:ayanlj1981@163.com
基金资助:
河南省医学科技攻关计划(联合共建)项目(LHGJ20191495)

An analysis on the characteristics of Entecavir resistance mutation in patients with chronic hepatitis B

WANG Zhang-yun¹, WANG Yan-li², HE Xing-chang³

1. Department of Infection and Hepatology, Wuxi Branch of Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Jiangsu 214000, China;
2. Department of Infectious Diseases, Infectious Disease Hospital Affiliated to Zhengzhou University, Henan 450000;
3. Department of Hepatology,Shangqiu First People's Hospital,Henan 476100, China

Received:2024-07-23 Online:2024-12-31 Published:2025-02-19
Contact: WANG Yan-li, ,Email:ayanlj1981@163.com

摘要/Abstract

摘要： 目的探讨慢性乙型肝炎(CHB)患者恩替卡韦(ETV)基因型耐药突变模式及其临床特征分析。方法 2020年10月—2023年5月上海交通大学医学院附属瑞金医院无锡分院诊治的CHB患者121例,CHB诊断符合要求。耐药突变需要符合HBV耐药位点rtL180M、rtM204V阳性(或仅rtM204I阳性)并且rtV173、rtT184、rtS202、rtV169和rtV250中任一个或一个以上阳性;经过口服LAM(LAM)、替比夫定(Ldt)、阿德福韦酯(ADV)、ETV(ETV)及富马酸替诺福韦二吡呋酯(TDF)等至少一种抗病毒药物或序贯应用多种抗病毒药物治疗至少12个月后HBV DNA至少处于低病毒状态。研究中抗病毒方案接受NAs治疗包括单药治疗、联合治疗和序贯治疗。结果 121例患者中ETV基因型耐药突变46例,耐药率为38.0%。具体耐药突变位点及其突变模式包括rtT184A/M204V/L180M 9例(19.6%)、rtT184L/M204V/L180M 8例(17.4%)、rtT184S/M204V/L180M 1例(2.2%)、rtS202G/M204V/L180M 18例(39.1%)、rtS202G/M204I/M240I 3例(6.5%)、rtM250V/M204V/L180M 3例(6.5%)、rtM250L/M204V/M204I 2例(4.3%)及rtT184/S202/M204V/L180M 2例(4.3%)。ETV基因型耐药突变患者使用NAs情况为LAM 17例(37.0%)、ADV 15例(32.6%)、Ldt 4例(8.7%)、ETV 3例(6.5%)、TDF 2例(4.3%),其余5例(10.7%)为联合或序贯治疗使用,以LAM、ADV为主。使用LAM耐药突变患者rtT184突变为11例(64.7%),显著高于ADV[3例(20.0%)],差异具有统计学意义(P<0.05)。结论 ETV耐药患者的主要基因突变模式为rtS202G/L180M突变,患者在接受NAs药物治疗过程中应接受谨慎周密的临床评估,防止耐药株的产生。

关键词: 慢性乙型肝炎, 恩替卡韦, 耐药

Abstract: Objective To explore the entecavir resistance mutation pattern and its clinical characteristics in patients with chronic hepatitis B.Methods Between October 2020 and May 2023, 121 patients were diagnosed with CHB and treated in Wuxi Branch of Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine. Drug-resistant mutations need to be positive for rtL180M, rtM204V (or only rtM204I) and any one or more of rtV173, rtT184, rtS202, rtV169 and rtV250; After at least 12 months of oral treatment with at least one antiviral drug such as lamivudine (LAM), telbivudine (Ldt), adefovir dipivoxil (ADV), entecavir (ETV) and tenofovir dipivoxil fumarate (TDF), HBV DNA is at least in a low viral load status. In the study, the antiviral regimen received NAs treatment including single drug therapy, combined therapy and sequential therapy.Results Among 121 patients, there were 46 cases of ETV drug-resistant mutation, and the drug-resistant rate was 38.0%. Specific drug-resistant mutation sites and their mutation patterns include 9 cases of rtT184A/M204V/L180M (19.6%), 8 cases of rtT184L/M204V/L180M (17.4%), 1 case of rtT184S/M204V/L180M (2.2%), 18 cases of rtS202g/M204V/L180m (39.1%), 3 cases of rtS202G/M204I/M240I (6.5%), 3 cases of rtM250V/M204V/L180M (6.5%), 2 cases of rtM250L/M204V/M204I (4.3%) and 2 cases of rtT184/S202/M204V/L180M (4.3%). In patients with drug-resistant mutations of ETV, 17 cases were shift to LAM (37.0%), 15 cases were shift to ADV (32.6%), 4 cases were shift to LDT (8.7%), 3 cases were shift to ETV (6.5%), 2 cases were shift to TDF (4.3%), and the remaining 5 cases (10.7%) were shift to combined or sequential therapy. There were 11 cases (64.7%) with rtT184 mutation in LAM-resistant patients, which was significantly higher than that in ADV-resistant patients [3 cases (20.0%)], and the difference was statistically significant (P<0.05).Conclusion The main gene mutation pattern of entecavir-resistant patients is rtS202G/L180M mutation. Patients should receive careful clinical evaluation during treatment with NAs to prevent the emergence of drug-resistant strains.

Key words: Chronic hepatitis B, Entecavir, Drug resistance

王章云, 王延丽, 何行昌. 慢性乙型肝炎患者恩替卡韦基因型耐药突变模式及其结果分析[J]. 肝脏, 2024, 29(12): 1472-1475.

WANG Zhang-yun, WANG Yan-li, HE Xing-chang. An analysis on the characteristics of Entecavir resistance mutation in patients with chronic hepatitis B[J]. Chinese Hepatolgy, 2024, 29(12): 1472-1475.

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