基于乙型肝炎病毒前基因组 RNA 的核苷酸序列,慢性乙型肝炎患者从水合恩替卡韦加富马酸替诺福韦阿非那酰胺联合疗法转为富马酸替诺福韦阿非那酰胺单药疗法。

IF 3.9 3区 医学 Q1 GASTROENTEROLOGY & HEPATOLOGY
Shunsuke Yamada, Yoshihito Uchida, Jun-Ichi Kouyama, Kayoko Naiki, Shohei Tsuji, Hayato Uemura, Kayoko Sugawara, Nobuaki Nakayama, Yukinori Imai, Tomoaki Tomiya, Suguru Mizuno, Satoshi Mochida
{"title":"基于乙型肝炎病毒前基因组 RNA 的核苷酸序列,慢性乙型肝炎患者从水合恩替卡韦加富马酸替诺福韦阿非那酰胺联合疗法转为富马酸替诺福韦阿非那酰胺单药疗法。","authors":"Shunsuke Yamada,&nbsp;Yoshihito Uchida,&nbsp;Jun-Ichi Kouyama,&nbsp;Kayoko Naiki,&nbsp;Shohei Tsuji,&nbsp;Hayato Uemura,&nbsp;Kayoko Sugawara,&nbsp;Nobuaki Nakayama,&nbsp;Yukinori Imai,&nbsp;Tomoaki Tomiya,&nbsp;Suguru Mizuno,&nbsp;Satoshi Mochida","doi":"10.1111/hepr.14036","DOIUrl":null,"url":null,"abstract":"<div>\n \n \n <section>\n \n <h3> Aim</h3>\n \n <p>Patients with chronic hepatitis B virus (HBV) infection experiencing viral breakthrough (BTH) or partial response (PR) during lamivudine (LAM) or entecavir hydrate (ETV) administration often took ETV plus tenofovir alafenamide fumarate (TAF) due to the emergence of a drug-resistance mutation. However, in patients lacking drug-resistance mutation against TAF, sufficient antiviral effects may be achievable with TAF monotherapy. We assessed the drug-resistance profile through nucleotide sequences of HBV pregenome RNA, and subsequently changed to TAF monotherapy from ETV plus TAF.</p>\n </section>\n \n <section>\n \n <h3> Methods</h3>\n \n <p>This prospective study included 25 patients with serum HBV-DNA below 20 IU/mL under ETV plus TAF administration. Pregenome RNA nucleotide sequences of HBV in the sera were analyzed using direct sequencing and deep sequencing. ETV was discontinued in patients without rtA194T and rtS106C + rtH126Y + rtD134E + rtL269I quadruple mutations in direct sequencing.</p>\n </section>\n \n <section>\n \n <h3> Results</h3>\n \n <p>LAM-PR, LAM-BTH, ETV-PR, and ETV-BTH were observed in 1, 16, 7, and 1 patient(s), respectively. Pregenome RNA nucleotide sequences were analyzable in 20 patients. Among the 12 patients classified as LAM-BTH, six patients showed rtL180M + rtM204V/I in direct sequencing, and one patient showed minor clones containing rtL180M + rtM204V + A194T in deep sequencing at a frequency of 0.3%. In the six patients classified as ETV-PR, one patient harbored rtM204I. No clones showing rtS106C + rtH126Y + rtD134E + rtL269I quadruple mutation were detected in deep sequencing. Subsequently, ETV was discontinued, and serum HBV-DNA remained undetectable up to 48 weeks in all patients.</p>\n </section>\n \n <section>\n \n <h3> Conclusion</h3>\n \n <p>Patients receiving ETV plus TAF due to partial response or BTH during initial LAM or ETV administration were able to safely transition to TAF monotherapy based on nucleotide sequences of HBV pregenome RNA in the sera.</p>\n </section>\n </div>","PeriodicalId":12987,"journal":{"name":"Hepatology Research","volume":null,"pages":null},"PeriodicalIF":3.9000,"publicationDate":"2024-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/hepr.14036","citationCount":"0","resultStr":"{\"title\":\"Switching from combination therapy with entecavir hydrate plus tenofovir alafenamide fumarate to tenofovir alafenamide fumarate monotherapy in patients with chronic hepatitis B based on nucleotide sequences of hepatitis B virus pregenome RNA\",\"authors\":\"Shunsuke Yamada,&nbsp;Yoshihito Uchida,&nbsp;Jun-Ichi Kouyama,&nbsp;Kayoko Naiki,&nbsp;Shohei Tsuji,&nbsp;Hayato Uemura,&nbsp;Kayoko Sugawara,&nbsp;Nobuaki Nakayama,&nbsp;Yukinori Imai,&nbsp;Tomoaki Tomiya,&nbsp;Suguru Mizuno,&nbsp;Satoshi Mochida\",\"doi\":\"10.1111/hepr.14036\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div>\\n \\n \\n <section>\\n \\n <h3> Aim</h3>\\n \\n <p>Patients with chronic hepatitis B virus (HBV) infection experiencing viral breakthrough (BTH) or partial response (PR) during lamivudine (LAM) or entecavir hydrate (ETV) administration often took ETV plus tenofovir alafenamide fumarate (TAF) due to the emergence of a drug-resistance mutation. However, in patients lacking drug-resistance mutation against TAF, sufficient antiviral effects may be achievable with TAF monotherapy. We assessed the drug-resistance profile through nucleotide sequences of HBV pregenome RNA, and subsequently changed to TAF monotherapy from ETV plus TAF.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Methods</h3>\\n \\n <p>This prospective study included 25 patients with serum HBV-DNA below 20 IU/mL under ETV plus TAF administration. Pregenome RNA nucleotide sequences of HBV in the sera were analyzed using direct sequencing and deep sequencing. ETV was discontinued in patients without rtA194T and rtS106C + rtH126Y + rtD134E + rtL269I quadruple mutations in direct sequencing.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Results</h3>\\n \\n <p>LAM-PR, LAM-BTH, ETV-PR, and ETV-BTH were observed in 1, 16, 7, and 1 patient(s), respectively. Pregenome RNA nucleotide sequences were analyzable in 20 patients. Among the 12 patients classified as LAM-BTH, six patients showed rtL180M + rtM204V/I in direct sequencing, and one patient showed minor clones containing rtL180M + rtM204V + A194T in deep sequencing at a frequency of 0.3%. In the six patients classified as ETV-PR, one patient harbored rtM204I. No clones showing rtS106C + rtH126Y + rtD134E + rtL269I quadruple mutation were detected in deep sequencing. Subsequently, ETV was discontinued, and serum HBV-DNA remained undetectable up to 48 weeks in all patients.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Conclusion</h3>\\n \\n <p>Patients receiving ETV plus TAF due to partial response or BTH during initial LAM or ETV administration were able to safely transition to TAF monotherapy based on nucleotide sequences of HBV pregenome RNA in the sera.</p>\\n </section>\\n </div>\",\"PeriodicalId\":12987,\"journal\":{\"name\":\"Hepatology Research\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":3.9000,\"publicationDate\":\"2024-03-22\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://onlinelibrary.wiley.com/doi/epdf/10.1111/hepr.14036\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Hepatology Research\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://onlinelibrary.wiley.com/doi/10.1111/hepr.14036\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"GASTROENTEROLOGY & HEPATOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Hepatology Research","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1111/hepr.14036","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"GASTROENTEROLOGY & HEPATOLOGY","Score":null,"Total":0}
引用次数: 0

摘要

目的:慢性乙型肝炎病毒(HBV)感染患者在服用拉米夫定(LAM)或恩替卡韦水合物(ETV)期间出现病毒突破(BTH)或部分应答(PR)时,由于出现耐药突变,通常会在服用 ETV 的同时服用富马酸替诺福韦阿非那胺(TAF)。然而,对于对 TAF 缺乏耐药性突变的患者,单用 TAF 治疗也能达到足够的抗病毒效果。我们通过HBV前基因组RNA的核苷酸序列评估了耐药情况,随后将ETV加TAF改为TAF单药治疗:这项前瞻性研究纳入了25名血清HBV-DNA低于20 IU/mL、接受ETV加TAF治疗的患者。采用直接测序法和深度测序法分析了血清中 HBV 的前基因组 RNA 核苷酸序列。在直接测序中未发现 rtA194T 和 rtS106C + rtH126Y + rtD134E + rtL269I 四重突变的患者停用 ETV:在 1、16、7 和 1 例患者中分别观察到 LAM-PR、LAM-BTH、ETV-PR 和 ETV-BTH。20名患者的前基因组RNA核苷酸序列可进行分析。在被归类为LAM-BTH的12名患者中,有6名患者在直接测序中显示出rtL180M + rtM204V/I,1名患者在深度测序中显示出含有rtL180M + rtM204V + A194T的小克隆,频率为0.3%。在归类为 ETV-PR 的六名患者中,有一名患者携带 rtM204I。在深度测序中未检测到出现 rtS106C + rtH126Y + rtD134E + rtL269I 四重突变的克隆。随后,停用了 ETV,所有患者的血清 HBV-DNA 均在 48 周内检测不到:结论:根据血清中 HBV 前基因组 RNA 的核苷酸序列,因部分应答或在初始 LAM 或 ETV 治疗期间出现 BTH 而接受 ETV 加 TAF 治疗的患者能够安全地过渡到 TAF 单药治疗。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Switching from combination therapy with entecavir hydrate plus tenofovir alafenamide fumarate to tenofovir alafenamide fumarate monotherapy in patients with chronic hepatitis B based on nucleotide sequences of hepatitis B virus pregenome RNA

Switching from combination therapy with entecavir hydrate plus tenofovir alafenamide fumarate to tenofovir alafenamide fumarate monotherapy in patients with chronic hepatitis B based on nucleotide sequences of hepatitis B virus pregenome RNA

Switching from combination therapy with entecavir hydrate plus tenofovir alafenamide fumarate to tenofovir alafenamide fumarate monotherapy in patients with chronic hepatitis B based on nucleotide sequences of hepatitis B virus pregenome RNA

Aim

Patients with chronic hepatitis B virus (HBV) infection experiencing viral breakthrough (BTH) or partial response (PR) during lamivudine (LAM) or entecavir hydrate (ETV) administration often took ETV plus tenofovir alafenamide fumarate (TAF) due to the emergence of a drug-resistance mutation. However, in patients lacking drug-resistance mutation against TAF, sufficient antiviral effects may be achievable with TAF monotherapy. We assessed the drug-resistance profile through nucleotide sequences of HBV pregenome RNA, and subsequently changed to TAF monotherapy from ETV plus TAF.

Methods

This prospective study included 25 patients with serum HBV-DNA below 20 IU/mL under ETV plus TAF administration. Pregenome RNA nucleotide sequences of HBV in the sera were analyzed using direct sequencing and deep sequencing. ETV was discontinued in patients without rtA194T and rtS106C + rtH126Y + rtD134E + rtL269I quadruple mutations in direct sequencing.

Results

LAM-PR, LAM-BTH, ETV-PR, and ETV-BTH were observed in 1, 16, 7, and 1 patient(s), respectively. Pregenome RNA nucleotide sequences were analyzable in 20 patients. Among the 12 patients classified as LAM-BTH, six patients showed rtL180M + rtM204V/I in direct sequencing, and one patient showed minor clones containing rtL180M + rtM204V + A194T in deep sequencing at a frequency of 0.3%. In the six patients classified as ETV-PR, one patient harbored rtM204I. No clones showing rtS106C + rtH126Y + rtD134E + rtL269I quadruple mutation were detected in deep sequencing. Subsequently, ETV was discontinued, and serum HBV-DNA remained undetectable up to 48 weeks in all patients.

Conclusion

Patients receiving ETV plus TAF due to partial response or BTH during initial LAM or ETV administration were able to safely transition to TAF monotherapy based on nucleotide sequences of HBV pregenome RNA in the sera.

求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
Hepatology Research
Hepatology Research 医学-胃肠肝病学
CiteScore
8.30
自引率
14.30%
发文量
124
审稿时长
1 months
期刊介绍: Hepatology Research (formerly International Hepatology Communications) is the official journal of the Japan Society of Hepatology, and publishes original articles, reviews and short comunications dealing with hepatology. Reviews or mini-reviews are especially welcomed from those areas within hepatology undergoing rapid changes. Short communications should contain concise definitive information.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信