PMID- 29630974
OWN - NLM
STAT- MEDLINE
DCOM- 20190729
LR  - 20190729
IS  - 1872-9096 (Electronic)
IS  - 0166-3542 (Linking)
VI  - 154
DP  - 2018 Jun
TI  - Hepatitis B virus rtA181T/sW172non-stop mutation may increase resistance fold to 
      adefovir- and entecavir-resistant mutants compared to rtA181T/sW172* mutation.
PG  - 26-34
LID - S0166-3542(17)30787-8 [pii]
LID - 10.1016/j.antiviral.2018.04.003 [doi]
AB  - The study aimed to characterize rtA181T/sW172stop (*) and rtA181T/sW172non-stop 
      mutations of hepatitis B virus (HBV). Total of 22,009 patients who visited 
      Beijing 302 Hospital from 2007 to 2016 were enrolled. These patients all received 
      nucleos(t)ide analogues (NAs) treatment and their serum samples were collected 
      for sequence analysis of HBV reverse-transcriptase (RT) and S regions. The 
      rtA181T mutation was detected in 5.37% (1182/22,009) of the patients' samples. 
      The rtA181T-causative sW172*, sW172non-stop (sW172 L/S), and mixed 
      sW172*/non-stop mutations occupied 82.91%, 7.70%, and 9.39%, respectively. The 
      patients with rtA181T/sW172non-stop mutants had a higher HBV DNA level compared 
      to those with rtA181T/sW172* mutants. 44.33% (524/1182) rtA181T-positive samples 
      were detected with signature drug-resistant mutations, including 325 with 
      adefovir-resistant mutation rtA181V/N236T, 57 with lamivudine-resistant mutation 
      rtM204V/I, 99 with entecavir-resistant mutation rtM204V/I plus rt184/202/250 
      substitution(s), and 43 with multidrug-resistant mutation 
      rtA181V/N236T + rtM204V/I +/- rt184/202/250 substitution(s). The 
      rtA181T/sW172non-stop mutation had a higher ratio of coexistence with 
      adefovir-resistant mutation compared to rtA181T/sW172* mutation (42.86% vs. 
      24.59%, P < 0.05). rtA181T/sW172S + rtN236T and rtA181T/sW172L + rtN236T mutants 
      exhibited higher HBV DNA production and adefovir resistance fold than that of 
      rtA181T/sW172* + rtN236T mutant (98.02% and 85.5% vs. 42.1% in HBV DNA 
      production, and 7.38-fold and 5.49-fold vs. 3.69-fold in half maximal effective 
      concentration of wild-type strain); rtA181T/sW172L + rtS202G + rtM204V strain 
      exhibited higher HBV DNA production and entecavir resistance fold than that of 
      rtA181T/sW172* + rtS202G + rtM204V strain (50.98% vs. 34.49%, 524.00-fold vs. 
      69.33-fold). In conclusion, rtA181T/sW172non-stop mutation may increase 
      resistance fold of adefovir- and entecavir-resistant mutants compared to 
      rtA181T/sW172* mutation and might influence clinical presentation of NAs-treated 
      patients.
CI  - Copyright (c) 2018. Published by Elsevier B.V.
FAU - Zhao, Li
AU  - Zhao L
AD  - Research Center for Clinical and Translational Medicine, Beijing 302 Hospital, 
      Beijing 100039, China; Clinical Medical School, Guilin Medical University, Guilin 
      541004, Guangxi Zhuang Autonomous Region, China.
FAU - Li, Xiaodong
AU  - Li X
AD  - Research Center for Clinical and Translational Medicine, Beijing 302 Hospital, 
      Beijing 100039, China.
FAU - Cheng, Yongqian
AU  - Cheng Y
AD  - Institute of Infectious Diseases, Beijing 302 Hospital, Beijing 100039, China.
FAU - Chen, Rongjuan
AU  - Chen R
AD  - Research Center for Clinical and Translational Medicine, Beijing 302 Hospital, 
      Beijing 100039, China.
FAU - Shao, Jinman
AU  - Shao J
AD  - Research Center for Clinical and Translational Medicine, Beijing 302 Hospital, 
      Beijing 100039, China.
FAU - Zhou, Yi
AU  - Zhou Y
AD  - Research Center for Clinical and Translational Medicine, Beijing 302 Hospital, 
      Beijing 100039, China.
FAU - Li, Qi
AU  - Li Q
AD  - Clinical Medical School, Guilin Medical University, Guilin 541004, Guangxi Zhuang 
      Autonomous Region, China.
FAU - Liao, Hao
AU  - Liao H
AD  - Institute of Infectious Diseases, Beijing 302 Hospital, Beijing 100039, China.
FAU - Zhao, Yangyang
AU  - Zhao Y
AD  - Research Center for Clinical and Translational Medicine, Beijing 302 Hospital, 
      Beijing 100039, China.
FAU - Liu, Lujie
AU  - Liu L
AD  - Research Center for Clinical and Translational Medicine, Beijing 302 Hospital, 
      Beijing 100039, China.
FAU - Su, Heling
AU  - Su H
AD  - Clinical Medical School, Guilin Medical University, Guilin 541004, Guangxi Zhuang 
      Autonomous Region, China.
FAU - Liu, Yongming
AU  - Liu Y
AD  - Clinical Medical School, Guilin Medical University, Guilin 541004, Guangxi Zhuang 
      Autonomous Region, China.
FAU - Liu, Yan
AU  - Liu Y
AD  - Research Center for Clinical and Translational Medicine, Beijing 302 Hospital, 
      Beijing 100039, China. Electronic address: liuyan5360@163.com.
FAU - Xu, Dongping
AU  - Xu D
AD  - Research Center for Clinical and Translational Medicine, Beijing 302 Hospital, 
      Beijing 100039, China; Clinical Medical School, Guilin Medical University, Guilin 
      541004, Guangxi Zhuang Autonomous Region, China; Institute of Infectious 
      Diseases, Beijing 302 Hospital, Beijing 100039, China. Electronic address: 
      xudongping302@sina.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20180406
PL  - Netherlands
TA  - Antiviral Res
JT  - Antiviral research
JID - 8109699
RN  - 0 (Antiviral Agents)
RN  - 0 (DNA, Viral)
RN  - 0 (Organophosphonates)
RN  - 5968Y6H45M (entecavir)
RN  - 5Z93L87A1R (Guanine)
RN  - 6GQP90I798 (adefovir)
RN  - EC 2.7.7.49 (RNA-Directed DNA Polymerase)
RN  - JAC85A2161 (Adenine)
MH  - Adenine/*analogs & derivatives/pharmacology
MH  - Adult
MH  - Antiviral Agents/*pharmacology
MH  - DNA, Viral/genetics
MH  - Drug Resistance, Viral/*genetics
MH  - Female
MH  - Genotype
MH  - Guanine/*analogs & derivatives/pharmacology
MH  - Hepatitis B virus/*drug effects/*genetics
MH  - Hepatitis B, Chronic/drug therapy
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Mutation
MH  - Organophosphonates/*pharmacology
MH  - RNA-Directed DNA Polymerase/genetics
OTO - NOTNLM
OT  - Adefovir
OT  - Entecavir
OT  - Hepatitis B virus
OT  - Resistance
OT  - rtA181T/sW172 mutation
EDAT- 2018/04/10 06:00
MHDA- 2019/07/30 06:00
CRDT- 2018/04/10 06:00
PHST- 2017/11/22 00:00 [received]
PHST- 2018/03/07 00:00 [revised]
PHST- 2018/04/03 00:00 [accepted]
PHST- 2018/04/10 06:00 [pubmed]
PHST- 2019/07/30 06:00 [medline]
PHST- 2018/04/10 06:00 [entrez]
AID - S0166-3542(17)30787-8 [pii]
AID - 10.1016/j.antiviral.2018.04.003 [doi]
PST - ppublish
SO  - Antiviral Res. 2018 Jun;154:26-34. doi: 10.1016/j.antiviral.2018.04.003. Epub 
      2018 Apr 6.