Lan-Lan Si, Zhen-Ping Fan, Wen-Hui Liu, Rong-Juan Chen, Xue-Yuan Chen, Dong Ji, Le Li, Chun Chen, Hao Liao, Jun Wang, Dong-Ping Xu, Jun Zhao, Yan Liu
{"title":"乙型肝炎病毒rtCYE/rtCYEI突变可能导致有限的替诺福韦耐药性：对中国患者大样本的分析","authors":"Lan-Lan Si, Zhen-Ping Fan, Wen-Hui Liu, Rong-Juan Chen, Xue-Yuan Chen, Dong Ji, Le Li, Chun Chen, Hao Liao, Jun Wang, Dong-Ping Xu, Jun Zhao, Yan Liu","doi":"10.4254/wjh.v17.i8.107456","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Whether rtS106C+H126Y+D134E/rtS106C+H126Y+D134E+L269I (rtCYE/rtCYEI) mutations in the hepatitis B virus (HBV) reverse-transcriptase (RT) region are associated with tenofovir disoproxil fumarate (TDF) resistance is controversial.</p><p><strong>Aim: </strong>To evaluate the presence of the rtCYE/rtCYEI mutations in a large cohort of Chinese patients with chronic HBV infection.</p><p><strong>Methods: </strong>A total of 28236 patients who underwent drug resistance testing at the Fifth Medical Center of Chinese PLA General Hospital from 2007 to 2019 were enrolled. All patients received nucleoside/nucleotide analogues (NAs) therapy, and serum samples were collected for sequence analysis of the HBV RT domain with mutation analysis.</p><p><strong>Results: </strong>The detection rates of a single mutation of rtS106C, rtH126Y, rtD134E, and rtL269I were 8.21%, 3.20%, 2.55% and 61.49% in 23718 genotype C patients, and 1.31%, 1.76%, 0.21%, and 92.33% in 4266 genotype B patients, respectively. The combined mutations of rtCYE/rtCYEI were only detected in 12 genotype C patients, accounting for 0.042% of all patients. These 12 patients had received NA treatments except TDF before testing. Among them, 6 patients had coexisting rtCYE/rtCYEI and lamivudine-resistance mutations, and 2 patients had coexisting rtCYE/rtCYEI and adefovir-resistance mutations. Compared with the wild-type (WT) strain, the replication capacity of rtCYE/rtCYEI mutants from representative patients decreased by 41.1%-71.8%, and TDF susceptibility reduced by less than 2-fold, but rtCYEI+rtA181V/N236T mutants exhibited a 6.2-/9.9-fold decrease in TDF susceptibility. Molecular modeling showed that rtCYE/rtCYEI mutants had a slight decrease in binding energy to TDF compared to the WT strain. In the clinic, emergence of the rtCYE/rtCYEI mutations was not specifically associated with TDF treatment.</p><p><strong>Conclusion: </strong>HBV rtCYE/rtCYEI mutations have a limited effect on TDF susceptibility and are not sufficient to cause TDF resistance.</p>","PeriodicalId":23687,"journal":{"name":"World Journal of Hepatology","volume":"17 8","pages":"107456"},"PeriodicalIF":2.5000,"publicationDate":"2025-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12400389/pdf/","citationCount":"0","resultStr":"{\"title\":\"Hepatitis B virus rtCYE/rtCYEI mutations may contribute limited tenofovir resistance: Analysis of a large sample of Chinese patients.\",\"authors\":\"Lan-Lan Si, Zhen-Ping Fan, Wen-Hui Liu, Rong-Juan Chen, Xue-Yuan Chen, Dong Ji, Le Li, Chun Chen, Hao Liao, Jun Wang, Dong-Ping Xu, Jun Zhao, Yan Liu\",\"doi\":\"10.4254/wjh.v17.i8.107456\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Whether rtS106C+H126Y+D134E/rtS106C+H126Y+D134E+L269I (rtCYE/rtCYEI) mutations in the hepatitis B virus (HBV) reverse-transcriptase (RT) region are associated with tenofovir disoproxil fumarate (TDF) resistance is controversial.</p><p><strong>Aim: </strong>To evaluate the presence of the rtCYE/rtCYEI mutations in a large cohort of Chinese patients with chronic HBV infection.</p><p><strong>Methods: </strong>A total of 28236 patients who underwent drug resistance testing at the Fifth Medical Center of Chinese PLA General Hospital from 2007 to 2019 were enrolled. All patients received nucleoside/nucleotide analogues (NAs) therapy, and serum samples were collected for sequence analysis of the HBV RT domain with mutation analysis.</p><p><strong>Results: </strong>The detection rates of a single mutation of rtS106C, rtH126Y, rtD134E, and rtL269I were 8.21%, 3.20%, 2.55% and 61.49% in 23718 genotype C patients, and 1.31%, 1.76%, 0.21%, and 92.33% in 4266 genotype B patients, respectively. The combined mutations of rtCYE/rtCYEI were only detected in 12 genotype C patients, accounting for 0.042% of all patients. These 12 patients had received NA treatments except TDF before testing. Among them, 6 patients had coexisting rtCYE/rtCYEI and lamivudine-resistance mutations, and 2 patients had coexisting rtCYE/rtCYEI and adefovir-resistance mutations. Compared with the wild-type (WT) strain, the replication capacity of rtCYE/rtCYEI mutants from representative patients decreased by 41.1%-71.8%, and TDF susceptibility reduced by less than 2-fold, but rtCYEI+rtA181V/N236T mutants exhibited a 6.2-/9.9-fold decrease in TDF susceptibility. Molecular modeling showed that rtCYE/rtCYEI mutants had a slight decrease in binding energy to TDF compared to the WT strain. In the clinic, emergence of the rtCYE/rtCYEI mutations was not specifically associated with TDF treatment.</p><p><strong>Conclusion: </strong>HBV rtCYE/rtCYEI mutations have a limited effect on TDF susceptibility and are not sufficient to cause TDF resistance.</p>\",\"PeriodicalId\":23687,\"journal\":{\"name\":\"World Journal of Hepatology\",\"volume\":\"17 8\",\"pages\":\"107456\"},\"PeriodicalIF\":2.5000,\"publicationDate\":\"2025-08-27\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12400389/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"World Journal of Hepatology\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.4254/wjh.v17.i8.107456\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"GASTROENTEROLOGY & HEPATOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"World Journal of Hepatology","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.4254/wjh.v17.i8.107456","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"GASTROENTEROLOGY & HEPATOLOGY","Score":null,"Total":0}
Hepatitis B virus rtCYE/rtCYEI mutations may contribute limited tenofovir resistance: Analysis of a large sample of Chinese patients.
Background: Whether rtS106C+H126Y+D134E/rtS106C+H126Y+D134E+L269I (rtCYE/rtCYEI) mutations in the hepatitis B virus (HBV) reverse-transcriptase (RT) region are associated with tenofovir disoproxil fumarate (TDF) resistance is controversial.
Aim: To evaluate the presence of the rtCYE/rtCYEI mutations in a large cohort of Chinese patients with chronic HBV infection.
Methods: A total of 28236 patients who underwent drug resistance testing at the Fifth Medical Center of Chinese PLA General Hospital from 2007 to 2019 were enrolled. All patients received nucleoside/nucleotide analogues (NAs) therapy, and serum samples were collected for sequence analysis of the HBV RT domain with mutation analysis.
Results: The detection rates of a single mutation of rtS106C, rtH126Y, rtD134E, and rtL269I were 8.21%, 3.20%, 2.55% and 61.49% in 23718 genotype C patients, and 1.31%, 1.76%, 0.21%, and 92.33% in 4266 genotype B patients, respectively. The combined mutations of rtCYE/rtCYEI were only detected in 12 genotype C patients, accounting for 0.042% of all patients. These 12 patients had received NA treatments except TDF before testing. Among them, 6 patients had coexisting rtCYE/rtCYEI and lamivudine-resistance mutations, and 2 patients had coexisting rtCYE/rtCYEI and adefovir-resistance mutations. Compared with the wild-type (WT) strain, the replication capacity of rtCYE/rtCYEI mutants from representative patients decreased by 41.1%-71.8%, and TDF susceptibility reduced by less than 2-fold, but rtCYEI+rtA181V/N236T mutants exhibited a 6.2-/9.9-fold decrease in TDF susceptibility. Molecular modeling showed that rtCYE/rtCYEI mutants had a slight decrease in binding energy to TDF compared to the WT strain. In the clinic, emergence of the rtCYE/rtCYEI mutations was not specifically associated with TDF treatment.
Conclusion: HBV rtCYE/rtCYEI mutations have a limited effect on TDF susceptibility and are not sufficient to cause TDF resistance.
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