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Characteristics of resistance-associated mutation in treatment-experienced chronic hepatitis B patients with low-level viremia
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Jian-Jun Wang1, Dong Ji1, *, Le Li2, Lan-Lan Si2, Rong-Juan Chen2, Yuan-Hua Li1, Fei-Lin Ge1, Zeng-Tao Yao2, Dong-Ping Xu2, Yan Liu2, *
Medical Journal of Chinese People’s Liberation Army | 2023, 48(2) : 138 - 142
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Medical Journal of Chinese People’s Liberation Army | 2023, 48(2): 138-142
• The diagnosis, treatment and prognosis of chronic hepatitis B •
Characteristics of resistance-associated mutation in treatment-experienced chronic hepatitis B patients with low-level viremia
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Jian-Jun Wang1, Dong Ji1, *, Le Li2, Lan-Lan Si2, Rong-Juan Chen2, Yuan-Hua Li1, Fei-Lin Ge1, Zeng-Tao Yao2, Dong-Ping Xu2, Yan Liu2, *
Affiliations
  • 1Department of Liver Diseases, the Fifth Medical Center of Chinese PLA General Hospital, Beijing 100039, China
  • 2Department of Infectious Diseases, the Fifth Medical Center of Chinese PLA General Hospital, Beijing 100039, China
Published: 2023-02-28 doi: 10.11855/j.issn.0577-7402.2023.02.0138
Outline
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Objective To analyze the genotypic characteristics of resistance-associated mutation in reverse-transcriptase(RT) domain of hepatitis B virus (HBV) in treatment-experienced chronic hepatitis B (CHB) patients with low-level viremia (LLV). Methods CHB patients with LLV, who admitted to the Fifth Medical Center of Chinese PLA General Hospital from September 2007 to August 2019, were retrospectively enrolled. Their serum HBV DNA was extracted, and a nested PCR was used to amplify an HBV RT fragment, 1225 bp in length (nt54-nt1278), containing the HBV RT gene (nt130-nt1161) and S gene (nt155-nt835).PCR products were bidirectionally sequenced, and a molecular evolutionary tree analysis of the RT/S gene sequence was performed with MEGA 4 software, with the Hepacivirus database (http://www.ncbi.nlm.nih.gov/projects/genotyping/formpage.Cgi) with the standard sequence as the reference for HBV genotyping. Results Among the 2096 patients, 82.4% were male, mean age was(45.6±12.0) years, HBV DNA was (2.5±0.5) log10 IU/ml. Lamivudine resistance related mutations accounted for 58.0%, with M204V and L180M+M204V as the main forms; Adefovir dipivoxil resistance associated mutations accounted for 21.2%, with A181V and N36T as the predominant forms; Entecavir resistance associated mutations accounted for 17.9%, with L180M+M204I/V+T184L/A/S/I and L180M+M204V+S202G being the predominant forms; Multidrug resistance accounted for 2.9%, with L180M+M204I/V+A181V and L180M+M204V+A181V+N236T+S202G being the predominant forms. Conclusion Lamivudine and Adefovir resistance are the main drug-resistant mutation genotypes in the treated CHB patients with LLV, which reduces the gene barrier of entecavir resistance and increases the proportion of entecavir resistance. Therefore, the first-line nucleos(t)ide analogues with strong effect and low resistance should be selected for antiviral treatment.

hepatitis B, chronic  /  low level viremia  /  drug-resistant  /  mutation
Jian-Jun Wang, Dong Ji, Le Li, Lan-Lan Si, Rong-Juan Chen, Yuan-Hua Li, Fei-Lin Ge, Zeng-Tao Yao, Dong-Ping Xu, Yan Liu. Characteristics of resistance-associated mutation in treatment-experienced chronic hepatitis B patients with low-level viremia[J]. Medical Journal of Chinese People’s Liberation Army, 2023 , 48 (2) : 138 -142 . DOI: 10.11855/j.issn.0577-7402.2023.02.0138
Funding
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  • National Natural Science Foundation of China(81721002)
  • National Natural Science Foundation of China(81930110)
  • National Major Science and Technology Special Project of China(2018ZX10725506)
  • Capital Characteristic Clinic Project of Beijing Municipal Science and Technology Commission(Z181100001718034)
  • Medical Big Data and Artificial Intelligence Development Fund of Chinese PLA General Hospital(2019MBD-024)
  • Key Project of Jumei Special Fund for Hepatobiliary Disease Prevention and Treatment, China Social Assisstance Foundation(2018JM12603003)
Appendix
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Year 2023 volume 48 Issue 2
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202
86
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Article Info
doi: 10.11855/j.issn.0577-7402.2023.02.0138
  • Receive Date：2021-05-03
  • Online Date：2025-12-03
  • Published：2023-02-28
Article Data
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History
  • Received：2021-05-03
  • Accepted：2021-07-07
Funding
National Natural Science Foundation of China(81721002)
National Natural Science Foundation of China(81930110)
National Major Science and Technology Special Project of China(2018ZX10725506)
Capital Characteristic Clinic Project of Beijing Municipal Science and Technology Commission(Z181100001718034)
Medical Big Data and Artificial Intelligence Development Fund of Chinese PLA General Hospital(2019MBD-024)
Key Project of Jumei Special Fund for Hepatobiliary Disease Prevention and Treatment, China Social Assisstance Foundation(2018JM12603003)
Affiliations
    1Department of Liver Diseases, the Fifth Medical Center of Chinese PLA General Hospital, Beijing 100039, China
    2Department of Infectious Diseases, the Fifth Medical Center of Chinese PLA General Hospital, Beijing 100039, China

Corresponding:

* Liu Yan, E-mail:
Ji Dong, E-mail:
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表12种不同金属材料的力学参数
科
Family		 属数
Number of
genus		 种数
Number of
species		 占总种数比例
Percentage of
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Genus		 种数
Number of
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Percentage of total
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鹅膏菌科Amanitaceae 2 11 5.26 鹅膏菌属 Amanita 10 4.78
小菇科 Mycenaceae 2 12 5.74 丝盖伞属 Inocybe 5 2.39
多孔菌科 Polyporaceae 8 14 6.70 蜡蘑属 Laccaria 5 2.39
红菇科 Russulaceae 3 23 11.00 小皮伞属 Marasmius 6 2.87
小菇属 Mycena 11 5.26
光柄菇属 Pluteus 5 2.39
红菇属 Russula 17 8.13
栓菌属 Trametes 5 2.39
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