Antiviral drug resistance rates among patients with chronic hepatitis B infection
DOI:
https://doi.org/10.15584/ejcem.2023.2.13Keywords:
antiviral agents, antiviral drug resistance, chronic hepatitis B, hepatitis BAbstract
Introduction and aim. Chronic hepatitis B infection (CHB) affects millions of people around the world. Many clinicians find it challenging to choose therapeutic agents due to the mutations that occur in the hepatitis B virus (HBV) that cause drug resistance. Thus, the aim of this study was to determine the HBV resistance rates against the currently recommended first-line therapies in the region of our country where HBV prevalence is high.
Material and methods. A total of 96 patients (56 men and 40 women) with HBV infection were enrolled in the study. The serum samples collected from those were analyzed with real-time polymerase chain reaction analysis followed by pyrosequencing (PyroStar HBV Drug Resistance Test, Altona Diagnostics, Germany) for drug resistance mutations associated with lamivudine, adefovir, telbivudine, entecavir, and tenofovir.
Results. HBV drug-resistance mutations were investigated in 80 treatment-naïve and 16 treatment-experienced patients (6 entecavir, 4 PEGylated-interferon, 4 tenofovir, 2 lamivudine). None of the HBV-DNA samples had mutations cause to drug resistance were detected in any codons regions that were analyzed.
Conclusion. Antiviral resistance poses serious obstacles for clinicians in the treatment of CHB. Determining whether antiviral resistance exists in HBV is critical to choose the appropriate treatment agent.
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Ott JJ, Stevens GA, Groeger J, Wiersma ST. Global epidemiology of hepatitis B virus infection: new estimates of age-specific HBsAg seroprevalence and endemicity. Vaccine. 2012;30(12):2212-2219. doi: 10.1016/j.vaccine.2011.12.116
Liu SH, Seto WK, Lai CL, Yuen MF. Hepatitis B: treatment choice and monitoring for response and resistance. Expert Rev Gastroenterol Hepatol. 2016;10(6):697-707. doi: 10.1586/17474124.2016.1145547
Nayagam S, Thursz M, Sicuri E, et al. Requirements for global elimination of hepatitis B: a modelling study. Lancet Infect Dis. 2016;16(12):1399-1408. doi: 10.1016/S1473-3099(16)30204-3
Buti M, Roade L, Riveiro-Barciela M, Esteban R. Optimal management of chronic hepatitis B patients receiving nucleos(t)ide analogues. Liver Int. 2020;40, 1:15-21. doi: 10.1111/liv.14367
Terrault NA, Lok ASF, McMahon BJ, et al. Update on prevention, diagnosis, and treatment of chronic hepatitis B: AASLD 2018 hepatitis B guidance. Hepatology. 2018;67(4):1560-1599. doi: 10.1002/hep.29800
European Association for the Study of the Liver. 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(2):370-398. doi: 10.1016/j.jhep.2017.03.021
Choi YM, Lee SY, Kim BJ. Naturally occurring hepatitis B virus reverse transcriptase mutations related to potential antiviral drug resistance and liver disease progression. World J Gastroenterol. 2018;24(16):1708-1724. doi: 10.3748/wjg.v24.i16.1708
Tozun N, Ozdogan O, Cakaloglu Y, et al. Seroprevalence of hepatitis B and C virus infections and risk factors in Turkey: a fieldwork TURHEP study. Clin Microbiol Infect. 2015;21(11):1020-1026. doi: 10.1016/j.cmi.2015.06.028
Cornberg M, Lok AS, 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(3):539-557. doi: 10.1016/j.jhep.2019.11.003
Tang LSY, Covert E, Wilson E, Kottilil S. Chronic Hepatitis B Infection: A, JAMA. 2018;319(17):1802-1813. doi: 10.1001/jama.2018.3795
Chuang WL, Jia J, Chan HLY, et al. Responses are durable for up to 5 years after completion of peginterferon alfa-2a treatment in hepatitis B e antigen-positive patients. Aliment Pharmacol Ther. 2018;47(9):1306-1316. doi: 10.1111/apt.14595
Suzuki F, Suzuki Y, Hosaka T, et al. Efficacy of long-term tenofovir-based rescue therapy in patients with chronic hepatitis B refractory to nucleoside/nucleotide analogs. J Gastroenterol. 2017;52(5):641-651. doi: 10.1007/s00535-016-1270-5
Zhang Q, Chen J, Pan M, Liu J, Liu T, Zhou YH. Comparison of replication competence of wild-type and lamivudine-resistant hepatitis B virus isolates from a chronic hepatitis B patient. Virus Res. 2018;255:165-170. doi: 10.1016/j.virusres.2018.07.021
Wang M, Yuan L, Qiao B, Li Y. Two rescue therapies in lamivudine-resistant patients with chronic hepatitis B in the central China: adefovir monotherapy and adefovir plus lamivudine. Virus Genes. 2014;48(1):32-37. doi: 10.1007/s11262-013-1004-1
Hermans LE, Svicher V, Pas SD, et al. Combined Analysis of the Prevalence of Drug-Resistant Hepatitis B Virus in Antiviral Therapy-Experienced Patients in Europe (CAPRE). J Infect Dis. 2016;213(1):39-48. doi: 10.1093/infdis/jiv363
Meng T, Shi X, Gong X, et al. Analysis of the prevalence of drug-resistant hepatitis B virus in patients with antiviral therapy failure in a Chinese tertiary referral liver centre (2010-2014). J Glob Antimicrob Resist. 2017;8:74-81. doi: 10.1016/j.jgar.2016.10.012
Alacam S, Karabulut N, Yolcu A, et al. Evaluation of drug resistance mutations in patients with chronic hepatitis B. Folia Microbiol (Praha). 2019;64(2):237-243. Doi :10.1007/s12223-018-0650-z
Hadziyannis SJ, Tassopoulos NC, Heathcote EJ, et al. Long-term therapy with adefovir dipivoxil for HBeAg-negative chronic hepatitis B for up to 5 years. Gastroenterology. 2006;131(6):1743-1751. doi: 10.1053/j.gastro.2006.09.020
Chen CH, Wang JH, Lu SN, et al. Characteristics of adefovir resistance in patients with or without lamivudine-resistant hepatitis B virus treated with adefovir: a 4-year experience. Liver Int. 2011;31(2):206-214. doi: 10.1111/j.1478-3231.2010.02416.x
Fung SK, Chae HB, Fontana RJ, et al. Virologic response and resistance to adefovir in patients with chronic hepatitis B. J Hepatol. 2006;44(2):283-290. doi: 10.1016/j.jhep.2005.10.018
Lee YS, Suh DJ, Lim YS, et al. Increased risk of adefovir resistance in patients with lamivudine-resistant chronic hepatitis B after 48 weeks of adefovir dipivoxil monotherapy. Hepatology. 2006;43(6):1385-1391. doi: 10.1002/hep.21189
Lai CL, Leung N, Teo EK, et al. A 1-year trial of telbivudine, lamivudine, and the combination in patients with hepatitis B e antigen-positive chronic hepatitis B. Gastroenterology. 2005;129(2):528-536. doi: 10.1016/j.gastro.2005.05.053
Tacke F, Kroy DC. Treatment for hepatitis B in patients with drug resistance. Ann Transl Med. 2016;4(18):334. doi: 10.21037/atm.2016.09.19
Snow-Lampart A, Chappell B, Curtis M, et al. No resistance to tenofovir disoproxil fumarate detected after up to 144 weeks of therapy in patients monoinfected with chronic hepatitis B virus. Hepatology. 2011;53(3):763-773. doi: 10.1002/hep.24078
Marino A, Cosentino F, Ceccarelli M, et al. Entecavir resistance in a patient with treatment-naïve HBV: A case report. Mol Clin Oncol. 2021;14(6):113. doi: 10.3892/mco.2021.2275
Tenney DJ, Rose RE, Baldick CJ, et al. Long-term monitoring shows hepatitis B virus resistance to entecavir in nucleoside-naïve patients is rare through 5 years of therapy. Hepatology. 2009;49(5):1503-1514. doi: 10.1002/hep.22841
Suzuki F, Toyoda J, Katano Y, et al. Efficacy and safety of entecavir in lamivudine-refractory patients with chronic hepatitis B: randomized controlled trial in Japanese patients. J Gastroenterol Hepatol. 2008;23(9):1320-1326. doi: 10.1111/j.1440-1746.2008.05455.x
Zoulim F, Locarnini S. Hepatitis B virus resistance to nucleos(t)ide analogues. Gastroenterology. 2009;137(5):1593-608.e6082. doi: 10.1053/j.gastro.2009.08.063
Yıldız O, Aygen B, Demirtürk N, et al. Lamivudine resistance mutations in patients infected with hepatitis B virus genotype D. World J Gastroenterol. 2011;17(45):4987-4992. doi: 10.3748/wjg.v17.i45.
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