All Issue

2020 Vol.50, Issue 3

Review Article

Overview of anti-Hepatitis B virus agents
Hye-won Lee1
,
Yong-kwang Park1
,
Yongwook Choi1†
1Division of Viral Disease Research, Center for Infectious Disease Research, Korea National Institute of Health
*wook0202@korea.kr
30 September 2020. pp. 141-149
PDF XML Citation
Abstract

Since the first FDA approval of Lamivudine in 1998, many nucleo(t)side analogs such as Lamivudine, Adefovir, and Entecavir have been used. However, they only inhibit DNA synthesis, and if their administration is stopped a viral breakthrough can develop, making long-term administration necessary, ultimately followed by the development of resistance. Tenofovir has been developed and drug-resistant mutations have decreased significantly, but the problem of resistance due to long-term drug use still remains, along with the drug safety problem. In this review, we introduce the recent trend in the development of hepatitis B treatment agents and the Korea National Research Institute of Health (KNIH) research for the development of a novel treatment for hepatitis B (drug repositioning) without resistance and which targets the various life cycles of HBV.

Keywords
Hepatitis B virus
anti-HBV agents
Drug resistance
References
1

Kee MK, Shin YH, Kim K, Ahn SH. Hepatitis B virus cohort studies worldwide. Public Health Weekly Report 2018;11:5708-20.

2

Lin SYC, Magalis BR, Salemi M, Liu HF. Origin and dissemination of hepatitis B virus genotype C in East Asia revealed by phylodynamic analysis and historical correlates. J Viral Hepat 2019;26:145-54.

10.1111/jvh.1300630199591PMC7166934
3

Kim JH, Park YK, Park ES, Kim KH. Molecular diagnosis and treatment of drug-resistant hepatitis B virus. World J Gastroenterol 2014;20:5708-20.

10.3748/wjg.v20.i19.570824914332PMC4024781
4

Fanning GC, Zoulim F, Hou J, Bertoletti A. Therapeutic strategies for hepatitis B virus infection: towards a cure. Nat Rev Drug Discov 2019;18:827-44.

10.1038/s41573-019-0037-031455905
5

Lopatin U. Drugs in the Pipeline for HBV. Clin Liver Dis 2019;23:535-55.

10.1016/j.cld.2019.04.00631266626
6

Tang LSY, Covert E, Wilson E, Kottilil S. Chronic Hepatitis B Infection: A Review. JAMA 2018;319:1802-13.

10.1001/jama.2018.379529715359
7

Quercia R, Perno CF, Koteff J, Moore K, McCoig C, St Clair M, et al. Twenty-Five Years of Lamivudine: Current and Future Use for the Treatment of HIV-1 Infection. J Acquir Immune Defic Syndr 2018;78:125-35.

10.1097/QAI.000000000000166029474268PMC5959256
8

Yuen MF, Seto WK, Fung J, Wong DKH, Yuen JCH, Lai CL. Three years of continuous entecavir therapy in treatment-naïve chronic hepatitis B patients: viral suppression, viral resistance, and clinical safety. Am J Gastroenterol 2011;106:1264-71.

10.1038/ajg.2011.4521364549
9

European Association For The Study Of The Liver. EASL clinical practice guidelines: management of chronic hepatitis B virus infection. J hepatol 2012;57:167-85.

10.1016/j.jhep.2012.02.01022436845
10

Yoo BC, Kim JH, Chung YH, Lee KS, Paik SW, Ryu SH, et al. Twenty-four-week clevudine therapy showed potent and sustained antiviral activity in HBeAg-positive chronic hepatitis B. Hepatology 2007;45:1172-8.

10.1002/hep.2162917464992
11

Perry CM, Simpson D. Tenofovir disoproxil fumarate: in chronic hepatitis B. Drugs 2009;69:2245-56.

10.2165/10482940-000000000-0000019852527
12

De Clercq E, Holý A. Acyclic nucleoside phosphonates: a key class of antiviral drugs. Nat Rev Drug Discov 2005;4:928-40.

10.1038/nrd187716264436
13

Gish R, Jia JD, Locarnini S, Zoulim F. Selection of chronic hepatitis B therapy with high barrier to resistance. Lancet Infect Dis 2012;12:341-53.

10.1016/S1473-3099(11)70314-0
14

van Hemert FJ, Berkhout B, Zaaijer HL. Differential binding of tenofovir and adefovir to reverse transcriptase of hepatitis B virus. PLoS One 2014;9:e106324.

10.1371/journal.pone.010632425180507PMC4152281
15

Park ES, Lee AR, Kim DH, Lee JH, Yoo JJ, Ahn SH, et al. Identification of a quadruple mutation that confers tenofovir resistance in chronic hepatitis B patients. J Hepatol 2019;70:1093-102.

10.1016/j.jhep.2019.02.00630794889
16

Mak LY, Seto WK, Lai CL, Yuen MF. Pharmacokinetic Evaluation of Besifovir for the Treatment of HBV Infection. Expert Opin Drug Metab Toxicol 2018; 14:101-6.

10.1080/17425255.2018.141798329237296
17

Zoulim F, Locarnini S. Heaptitis B Resistance to Nucleos(t)ide Analogues. Gastroenterology 2009;137:1593-1608.

10.1053/j.gastro.2009.08.06319737565
18

Villet S, Pichoud C, Billioud G, Barraud L, Durantel S, Trépo C, et al. Impact of hepatitis B virus rtA181V/T mutants on hepatitis B treatment failure. J Hepatol 2008;48:747-55.

10.1016/j.jhep.2008.01.02718331765
19

Colonno RJ, Rose R, Baldick CJ, Levine S, Pokornowski K, Yu CF, et al. Entecavir resistance is rare in nucleoside naïve patients with hepatitis B. Hepatology 2006;44:1656-65.

10.1002/hep.2142217133475
20

Levine S, Hernandez D, Yamanaka G, Zhang S, Rose R, Weinheimer S et al. Efficacies of entecavir against lamivudine-resistant hepatitis B virus replication and recombinant polymerases in vitro. Antimicrob Agents Chemother 2002;46:2525-32.

10.1128/AAC.46.8.2525-2532.200212121928PMC127388
21

Locarnini S, Mason WS. Cellular and virological mechanisms of HBV drug resistance. J Hepatol 2006;44:422-31.

10.1016/j.jhep.2005.11.03616364492
22

Seifer M, Patty A, Serra I, Li B, Standring DN. Telbivudine, a nucleoside analog inhibitor of HBV polymerase, has a different in vitro cross-resistance profile than the nucleotide analog inhibitors adefovir and tenofovir. Antiviral Res 2009;81:147-55.

10.1016/j.antiviral.2008.10.00819028525
23

Kwon SY, Park YK, Ahn SH, Cho ES, Choe WH, Lee CH, et al. Identification and characterization of clevudine-resistant mutants of hepatitis B virus isolated from chronic hepatitis B patients. J Virol 2010;84:4494-503.

10.1128/JVI.02066-0920164224PMC2863790
24

Amini-Bavil-Olyaee S, Herbers U, Sheldon J, Luedde T, Trautwein C, Tacke F. The rtA194T polymerase mutation impacts viral replication and susceptibility to tenofovir in hepatitis B e antigen-positive and hepatitis B e antigen-negative hepatitis B virus strains. Hepatology 2009;49:1158-65.

10.1002/hep.2279019263474
25

Kreutz C. Hepatitis B virus mutants resistant to Tenofovir. Med Life Clin 2019;1:1009.

26

Lai CL, Ahn SH, Lee KS, Um SH, Cho M, Yoon SK, et al. Phase IIb multicentred randomised trial of besifovir (LB80380) versus entecavir in Asian patients with chronic hepatitis B. Gut 2014;63:996-1004.

10.1136/gutjnl-2013-30513823979965
27

Terrault NA, Bzowej NH, Chang KM, Hwang JP, Jonas MM, Murad MH. AASLD guidelines for treatment of chronic hepatitis B. Hepatology 2016;63:261-83.

10.1002/hep.2815626566064PMC5987259
28

European Association for the Study of the Liver. EASL 2017 Clinical Practice Guidelines on the management of hepatitis B virus infection. J Hepatol 2017;67:370-98.

29

Cornberg M, Lok ASF, Terrault NA, Zoulim F, 2019 EASL-AASLD HBV Treatment Endpoints Conference Faculty. Guidance for design and endpoints of clinical trials in chronic hepatitis B-report from the 2019 EASL-AASLD HBV treatment endpoints conference. J Hepatol 2020;72:539-57.

10.1016/j.jhep.2019.11.00331730789
Information
  • Publisher :The Korean Society for Microbiology and The Korean Society of Virology
  • Publisher(Ko) :대한미생물학회‧대한바이러스학회
  • Journal Title :JOURNAL OF BACTERIOLOGY AND VIROLOGY
  • Volume : 50
  • No :3
  • Pages :141-149
  • Received Date : 2020-09-02
  • Revised Date : 2020-09-23
  • Accepted Date : 2020-09-24
  • DOI :https://doi.org/10.4167/jbv.2020.50.3.141
Journal Informaiton JOURNAL OF BACTERIOLOGY AND VIROLOGY JOURNAL OF BACTERIOLOGY AND VIROLOGY
  • NRF
  • 임플란트학회 전용 배너
  • KOFST
  • crossref crossmark
  • crossref cited-by
  • crossref funder-registry
  • crosscheck
  • orcid
  • open access
  • ccl
Journal Informaiton Journal Informaiton - close