Skip to main content

Advertisement

SpringerLink
Log in

Role of Resistance Testing During Oral Antiviral Therapy of Chronic Hepatitis B

  • Hepatitis B: Therapeutics (P Martin, Section Editor)
  • Published:
Current Hepatitis Reports Aims and scope Submit manuscript

Abstract

Hepatitis B virus (HBV) DNA replication is an error prone mechanism and coupled with selection pressure from antiviral agents, emergence of resistance can be frequent. Antiviral drug resistance has been associated with treatment failure, and the widespread use of readily available antiviral agents with limited potency and low genetic barrier, the risk of emergence of multidrug resistant HBV makes the management of chronic hepatitis B (CHB) challenging. Studies have shown that timely recognition of resistance and the introduction of appropriate antiviral therapy is associated with better clinical outcome. Genotypic resistance profiling is able to identify the cause of treatment failure and provide essential information on management options. It also enables clinicians to determine cross resistance and so implement therapy with the most favorable outcome. Currently genotypic resistance testing is not widely available and is costly. However, long-term benefits of resistance testing both in terms of clinical outcome and cost-effectiveness, are well recognized in other fields of medicine, and should be more readily available for patients with chronic hepatitis B

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

Papers of particular interest, published recently, have been highlighted as:••Of major importance

  1. Clercq ED. Antiviral drugs in current clinical use. J Clin Virol. 2004;30:115–33.

    Article  PubMed  Google Scholar 

  2. Greene WC, Debyserb Z, Ikeda Y. Novel targets for HIV therapy. Antivir Res. 2008;80:251–65.

    Article  PubMed  CAS  Google Scholar 

  3. Panel on Antiretroviral Guidelines for Adults and Adolescents Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents. Department of Health and Human Services. January 10. 2011. Available at http://www.aidsinfo.nih.gov/ContentFiles/AdultescentGL.pdf. Accessed on January 20, 2012.

  4. EASL. Clinical practice guidelines: management of chronic hepatitis B. J Hepatol. 2009;50:227–42.

    Article  Google Scholar 

  5. Yuen M, Sablon E, Hui C, Yuan H, Decraemer H, Lai CL. Factors associated with hepatitis B virus DNA breakthrough in patients receiving prolonged lamivudine therapy. Hepatology. 2001;34:785–91.

    Article  PubMed  CAS  Google Scholar 

  6. Durant J, Clevenbergh P, Halfon P, et al. Drug-resistance genotyping in HIV-1 therapy: the VIRAD APT randomised controlled trial. Lancet. 1999;353:2195–9.

    Article  PubMed  CAS  Google Scholar 

  7. Wensing AM, van de Vijver DA, Angarano G, Asjo B, Balotta C, Boeri E, et al. Prevalence of drug-resistant HIV-1 variants in untreated individuals in Europe: implications for clinical management. J Infect Dis. 2005;192:958–66.

    Article  PubMed  Google Scholar 

  8. Little SJ, Holte S, Routy JP, Daar ES, Markowitz M, Collier AC, et al. Antiretroviral-drug resistance among patients recently infected with HIV. N Engl J Med. 2002;347:385–94.

    Article  PubMed  CAS  Google Scholar 

  9. Corzillius M, Muhlberger N, Sroczynski G, Jaeger H, Wasem J, Siebert U. Cost effectiveness analysis of routine use of genotypic antiretroviral resistance testing after failure of antiretroviral treatment for HIV. Antivir Ther. 2004;9:27–36.

    PubMed  CAS  Google Scholar 

  10. Baxter J, Douglas M, Wentworth DN. A randomized study of antiretroviral management based on plasma genotypic antiretroviral resistance testing in patients failing therapy. AIDS. 2000;14:F83–93.

    Article  PubMed  CAS  Google Scholar 

  11. DeGruttola V, Dix L, D’Aquila R, et al. The relation between baseline HIV drug resistance and response to antiretroviral therapy: re-analysis of retrospective and prospective studies using a standardized data analysis plan. Antivir Ther. 2000;5:41–8.

    PubMed  CAS  Google Scholar 

  12. Wegner S, Wallace M, Aronson N, et al. Long-term efficacy of routine access to antiretroviral-resistance testing in HIV type 1–infected patients: results of the clinical efficacy of resistance testing trial. Clin Infect Dis. 2004;38:723–30.

    Article  PubMed  Google Scholar 

  13. Tural C, Ruiz L, Holtzer C, Schapiro J, Viciana P, Gonzalez J, et al. Clinical utility of HIV-1 genotyping and expert advice: the Havana trial. AIDS. 2002;16:209–18.

    Article  PubMed  Google Scholar 

  14. Weinstein MC, Goldie S, Losina E, et al. Use of genotypic resistance testing to guide HIV therapy: clinical impact and cost-effectiveness. Ann Intern Med. 2001;134:440–50.

    PubMed  CAS  Google Scholar 

  15. Fung S, Andreone P, Han S, Reddy RK, et al. Adefovir-resistant hepatitis B can be associated with viral rebound and hepatic decompensation. J Hepatol. 2005;43:937–43.

    Article  PubMed  CAS  Google Scholar 

  16. Hyung JY, Hussain M, Liu Y. Evolution of multi-drug resistant hepatitis B virus during sequential therapy. Hepatology. 2006;44:703–12.

    Article  Google Scholar 

  17. •• Wong V, Wong G, Tse CH, et al. Antiviral drug resistance testing in patients with chronic hepatitis B. Dig Dis Sci. 2011;57:221–31. This study showed approximately two thirds of patients undergoing genotypic resistance testing had antiviral drug associated resistance and subsequent management was altered in more than 50 % of cases based on the genotypic resistance profile knowledge.

    Article  PubMed  Google Scholar 

  18. Chainuvati S, Cheng J, Hou JL, et al. Patterns of managing chronic hepatitis B treatment-related rug resistance: a survey of physicians in Mainland China, South Korea, Taiwan and Thailand. Hepatol Int. 2009;3:453–60.

    Article  PubMed  Google Scholar 

  19. Locarnini S, Bowden S. Drug resistance in antiviral therapy. Clin Liver Dis. 2010;14:439–59.

    Article  PubMed  Google Scholar 

  20. Lee Y-S, Suh DJ, Lim Y-S, et al. Increased risk of adefovir resistance in patients with lamivudine-resistant chronic hepatitis B after 48 weeks of adefovir dipivoxil monotherapy. Hepatology. 2006;43:1385–91.

    Article  PubMed  CAS  Google Scholar 

  21. Warner N, Locarnini S. The antiviral drug selected hepatitis B virus rtA181T/sW172• mutant has a dominant negative secretion defect and alters the typical profile of viral rebound. Hepatology. 2008;48:88–98.

    Article  PubMed  CAS  Google Scholar 

  22. Warner N, Locarnini S, Kuiper M, Bartholomeusz A, Ayres A, Yuen L, et al. The L80I substitution in the reverse transcriptase domain of the hepatitis B virus polymerase is associated with lamivudine resistance and enhanced viral replication in vitro. Antimicrob Agents Chemother. 2007;51:2285–92.

    Article  PubMed  CAS  Google Scholar 

  23. Locarnini S. Molecular virology and the development of resistant mutants: implications for therapy. Semin Liver Dis. 2005;25 Suppl 1:9–19.

    Article  PubMed  CAS  Google Scholar 

  24. Chisari F, Ferrari C. Hepatitis B virus immunopathogenesis. Annu Rev Immunol. 1995;13:29–60.

    Article  PubMed  CAS  Google Scholar 

  25. Iloeje U, Yang H, Su J, Jen C, You S, Chen C. Predicting cirrhosis risk based on the level of circulating hepatitis B viral load. Gastroenterology. 2006;130:678–86.

    Article  PubMed  Google Scholar 

  26. Shaw T, Bartholomeusz A, Locarnini S. HBV drug resistance: mechanisms, detection and intepretation. J Hepatol. 2006;44:593–606.

    Article  PubMed  CAS  Google Scholar 

  27. Domingo E. Quasispecies and the development of new antiviral strategies. Progr Drug Res. 2003;60:133–58.

    Article  CAS  Google Scholar 

  28. Clavel F, Hance A. HIV drug resistance. N Engl J Med. 2004;350:1023–35.

    PubMed  CAS  Google Scholar 

  29. Dienstag JL, Perrillo R, Schiff E, et al. A preliminary trial of lamivudine for chronic hepatitis B infection. N Engl J Med. 1995;333:1657–61.

    Article  PubMed  CAS  Google Scholar 

  30. Dienstag JL, Schiff E, Wright T, et al. Lamivudine as initial treatment for chronic hepatitis B in the United States. N Engl J Med. 1999;341:1256–63.

    Article  PubMed  CAS  Google Scholar 

  31. Lai CL, Chien RN, Leung NW. A one-year trial of lamivudine for chronic hepatitis B. Asia Hepatitis Lamivudine Study Group. N Engl J Med. 1998;339:241–4.

    Article  Google Scholar 

  32. Lai CL, Dienstag JL, Schiff E. Prevalence and clinical correlates of YMDD variants during lamivudine therapy for patients with chronic hepatitis B. Clin Infect Dis. 2003;36:687–96.

    Article  PubMed  CAS  Google Scholar 

  33. •• Papatheodoris G, Lampertico P, Manolakopolous S, Lok A. Incidence of heptocellular carcinoma in chronic hepatitis B patients receiving nucleos(t)ide therapy: a systematic review. J Hepatol. 2010;53:348–56. This meta-analysis showed an increased risk of HCC in patients who failed to maintain virological remission. Furthermore, comparing antiviral naive patients to those with LMV resistance, whether or not cirrhosis was present, the rate of HCC was higher if there was LMV resistance as well.

    Article  Google Scholar 

  34. Liaw YF, Sung JJ, Chow WC, Farrell G, Lee CZ, Yuen H, et al. Lamivudine for patients with chronic hepatitis B and advanced liver disease. N Engl J Med. 2004;351:1521–31.

    Article  PubMed  CAS  Google Scholar 

  35. Thompson AJ, Ayres A, Yuen L, Bartholomeusz A, Bowden DS, Iser DM, et al. Lamivudine resistance in patients with chronic hepatitis B: role of clinical and virological factors. J Gastroenterol Hepatol. 2007;22:1078–85.

    Article  PubMed  CAS  Google Scholar 

  36. Delaney WET, Locarnini S, Shaw T. Resistance of hepatitis B virus to antiviral drugs: current aspects and directions for future investigation. Antivir Chem Chemother. 2001;12:1–35.

    PubMed  CAS  Google Scholar 

  37. Zoulim F, Locarnini S. Hepatitis B virus resistance to nucleos(t)ide analogues. Gastroenterology. 2009;137:1593–608.

    Article  PubMed  CAS  Google Scholar 

  38. Ogata N, Fujii K, Takigawa S. Novel patterns of amino acid mutations in the hepatitis B virus polymerase in association with resistance to lamivudine therapy in Japanese patients with chronic hepatitis B. J Med Virol. 1999;59:270–6.

    Article  PubMed  CAS  Google Scholar 

  39. Delaney W, Yang H, Westland CE, Das K, et al. The hepatitis B virus polymerase mutation rtV173L is selected during lamivudine therapy and enhances viral replication in vitro. J Virol. 2003;77:11833–43.

    Article  PubMed  CAS  Google Scholar 

  40. Angus PW, Locarnini SA, McCaughan GW, Jones RM, McMillan JS, Bowden DS. Hepatitis B virus precore mutant infection is associated with severe recurrent disease after liver transplantation. Hepatology. 1995;21:14–8.

    Article  PubMed  CAS  Google Scholar 

  41. Torresi J, Earnest-Silveira L, Civitico G, Walters TE, Lewin SR, Fyfe J, et al. Restoration of replication phenotype of lamivudine-resistant hepatitis B virus mutants by compensatory changes in the "fingers" subdomain of the viral polymerase selected as a consequence of mutations in the overlapping S gene. Virology. 2002;299:88–99.

    Article  PubMed  CAS  Google Scholar 

  42. Kamili Samili SV, Thompson G, Campbell K, Walker CM, Locarnini S, Krawczynski K. Efficacy of hepatitis B vaccine against antiviral drug-resistant hepatitis B virus mutants in the chimpanzee model. Hepatology. 2009;49:1483–92.

    Article  Google Scholar 

  43. Yang H, Qi X, Sabogal A, et al. Cross-resistance testing of next-generation nucleoside and nucleotide analogues against lamivudine- resistant HBV. Antivir Ther. 2005;10:625–33.

    PubMed  CAS  Google Scholar 

  44. Lai C-L, Gane E, Liaw YF, et al. Telbivudine versus lamivudine in patients with chronic hepatitis B. N Engl J Med. 2007;357:2576–88.

    Article  PubMed  CAS  Google Scholar 

  45. Liaw YF, Gane E, Leung N, et al. 2-year globe trial results: telbivudine is superior to lamivudine in patients with chronic hepatitis B. Gastroenterology. 2009;136:486–95.

    Article  PubMed  CAS  Google Scholar 

  46. Dando T, Plosker G. Adefovir dipivoxil. A review of its use in chronic HBVAdis drug evaluation. Drugs. 2003;63:2215–34.

    Article  PubMed  CAS  Google Scholar 

  47. Hadziyannis S, Tassopoulos N, Heathcote J, et al. Long-term therapy with adefovir dipivoxil for HBeAg-negative chronic hepatitis B for up to 5 years. Gastroenterology. 2006;131:1743–51.

    Article  PubMed  CAS  Google Scholar 

  48. Angus P, Vaughan R, Xiong S, Yang H, Delaney W, Gibbs C, et al. Resistance to adefovir dipivoxil therapy associated with the selection of a novel mutation in the HBV polymerase. Gastroenterology. 2003;125:292–7.

    Article  PubMed  Google Scholar 

  49. •• Patterson SJ, George J, Strasser SI, Lee AU, Sievert W, Nicoll AJ, et al. Tenofovir disoproxil fumarate rescue therapy following failure of both lamivudine and adefovir dipivoxil in chronic hepatitis B. Gut. 2011;60:247–54. This study showed TFV would be an appropriate antiviral agent in patients who had prior exposure to LMV and ADV with high rate of genotypic resistance, but if the patient was infected with HBV that had both rtA181T/V and rtN236T, then the virological response to TFV was sub-optimal, demonstrating the value of genotypic resistance testing.

    Article  PubMed  CAS  Google Scholar 

  50. Snow-Lampert A, Chappell B, Curtis M. No resistance to tenofovir disoproxil fumarate detected after up to 144 weeks of therapy in patients monoinfected with chronic hepatitis B virus. Hepatology. 2011;53:763–73.

    Article  Google Scholar 

  51. Lin P-F, Nowicka-Sans B, Terry B, et al. Entecavir exhibits inhibitory activity against human immunodeficiency virus under conditions of reduced viral challenge. Antimicrob Agents Chemother. 2008;52:1759–67.

    Article  PubMed  CAS  Google Scholar 

  52. McMahon M, Benjamin B, et al. The HBV drug entecavir—effects on HIV-1 replication and resistance. N Engl J Med. 2007;356:2614–21.

    Article  PubMed  CAS  Google Scholar 

  53. Levine S, Hernandez D, Yamanak G, Zhang S, Rose RE, et al. Efficacies of entecavir against lamivudine-resistant hepatitis b virus replication and recombinant polymerases in vitro. Antimicrob Agents Chemother. 2002;46:2525–32.

    Article  PubMed  CAS  Google Scholar 

  54. Woo G, Tomlinson G, Nishikawa Y, Kowgier M, Morris S, Wong D, et al. Tenofovir and entecavir are the most effective antiviral agents for chronic hepatitis B: a systematic review and bayesian meta-analyses. Gastroenterology. 2010;139:1218–29.

    Article  PubMed  CAS  Google Scholar 

  55. Tenney D, Rose R, Baldick C, Pokornowski K, Eggers B, Fang J, et al. Long-term monitoring shows hepatitis B virus resistance to entecavir in nucleoside-naive patients is rare through 5 years of therapy. Hepatology. 2009;49:1503–14.

    Article  PubMed  CAS  Google Scholar 

  56. Tenney DJ, Levine SM, Rose RE, Walsh AW, Weinheimer SP, Discotto L, et al. Clinical emergence of entecavir-resistant hepatitis B virus requires additional substitutions in virus already resistant to lamivudine. Antimicrob Agents Chemother. 2004;48:3498–507.

    Article  PubMed  CAS  Google Scholar 

  57. Villet S, Ollivet A, Pichoud C, Barraud L, Villeneuve J, Trepo C, et al. Stepwise process for the development of entecavir resistance in a chronic hepatitis B virus infected patient. 2007;46:531–8.

  58. Liu Y, Wang C, Zhong Y, Chen L, Li X, Ji D, et al. Evolution and suppression of HBV strains with multidrug resistance to lamivudine, adefovir dipivoxil and entecavir in a patient with chronic hepatitis B. Antivir Ther. 2010;15:1185–90.

    Article  PubMed  Google Scholar 

  59. Brunelle M, Jacquard A, Pichoud C, Durantel D, Carrouee-Durantel S, Villeneuve J, et al. Susceptibility to antivirals of a human HBV strain with mutations conferring resistance to both lamivudine and adefovir. Hepatology. 2005;41:1391–8.

    Article  PubMed  CAS  Google Scholar 

  60. Chang T, Lai CNEJM. Hepatitis B virus with primary resistance to adefovir. N Engl J Med. 2006;355:322–3.

    Article  PubMed  CAS  Google Scholar 

  61. Kim H, Han K, Ahn S, Kim E, Chang H, et al. Evaluation of methods for monitoring drug resistance in chronic hepatitis B patients during lamivudine therapy based on mass spectrometry and reverse hybridization. Antivir Ther. 2005;10:441–9.

    PubMed  CAS  Google Scholar 

  62. Hussain M, Fung S, Libbrecht E, Sablon E, Cursaro C, Andreone P, et al. Sensitive line probe assay that simultaneously detects mutations conveying resistance to lamivudine and adefovir. J Clin Microbiol. 2006;44:1094–7.

    Article  PubMed  CAS  Google Scholar 

  63. Jang H, Cho M, Heo J, Kim H, Jun H, Shin W, et al. Oligonucleotide chip for detection of lamivudine-resistant hepatitis B virus. J Clin Microbiol. 2004;42:4181–8.

    Article  PubMed  CAS  Google Scholar 

  64. Marrgeridon-Thermet S, Shulman NS, Ahmed A, et al. Ultra-deep pyrosequencing of hepatitis B virus quasispecies from nucleoside and nucleotide reverse-transcriptase inhibitor (NRTI)–treated patients and NRTI-naive patients. J Infect Dis. 2009;199:1275–85.

    Article  Google Scholar 

  65. Solmone M, Vincenti D, Prosperi M, Bruselles A, et al. Use of massively parallel ultradeep pyrosequencing to characterize the genetic diversity of hepatitis B virus in drug-resistant and drug-naive patients and to detect minor variants in reverse transcriptase and hepatitis B S antigen. 2009;83:1718–26.

  66. Zoulim F. In- vitro models for studying hepatitis B virus drug resistance. Liver Dis. 2006;26:171–80.

    Article  CAS  Google Scholar 

  67. Seigneres B, Pichoud C, Martin P, Furman P, Trepo C, Zoulim F. Inhibitory activity of dioxolane purine analogs on wild-type and lamivudine-resistant mutants of hepadnaviruses. Hepatology. 2002;36:710–22.

    Article  PubMed  CAS  Google Scholar 

  68. Durantel D, Carrouee-Durantel S, Werle-Lapostolle B, Brunelle M, Pichoud C, Trepo C, et al. A new strategy for studying in vitro the drug susceptibility of clinical isolates of human hepatitis B virus. Hepatology. 2004;40:855–64.

    PubMed  CAS  Google Scholar 

  69. Lok AS, Zoulim F, Locarnini S, Mangia A, Niro G, Decraemer H, et al. Monitoring drug resistance in chronic hepatitis B virus (HBV)-infected patients during lamivudine therapy: evaluation of performance of INNO-LiPA HBV DR assay. J Clin Microbiol. 2002;40:3729–34.

    Article  PubMed  CAS  Google Scholar 

  70. Yuen LK, Ayres A, Littlejohn M, Colledge D, Edgely A, Maskill WJ, et al. SeqHepB: a sequence analysis program and relational database system for chronic hepatitis B. Antivir Res. 2007;75:64–74.

    Article  PubMed  CAS  Google Scholar 

  71. Lok AS, Zoulim F, Locarnini S, Bartholomeusz A, Ghany MG, Pawlotsky JM, et al. Antiviral drug-resistant HBV: standardization of nomenclature and assays and recommendations for management. Hepatology. 2007;46:254–65.

    Article  PubMed  CAS  Google Scholar 

  72. Locarnini S, Hatzakis A, Heathcote J, Keeffe EB, Liang TJ, Mutimer D, et al. Management of antiviral resistance in patients with chronic hepatitis B. Antivir Ther. 2004;9:679–93.

    PubMed  CAS  Google Scholar 

  73. Carrouee-Durantel S, Durantel D, Werle-Lapostolle B, Pichoud C, Naesens L, Neyts J, et al. Suboptimal response to adefovir dipivoxil therapy for chronic hepatitis B in nucleoside-naive patients is not due to pre-existing drug-resistant mutants. Antivir Ther. 2008;13:381–8.

    PubMed  CAS  Google Scholar 

  74. Thibault V, Aubron-Olivier C, Agut H, Katlama C. Primary infection with a lamivudine-resistant hepatitis B virus. AIDS. 2002;16:131–3.

    Article  PubMed  Google Scholar 

  75. Besisik F, Karaca C, Akyuz F, et al. Occult HBV infection and YMDD variants in hemodialysis patients with chronic HCV infection. Hepatology. 2003;38:506.

    Google Scholar 

  76. Hayashi K, Katano Y, Ishigami M, Itoh A, Hirooka Y, Nakano I, et al. Prevalence and clinical characterization of patients with acute hepatitis B induced by lamivudine-resistant strains. J Gastroenterol Hepatol. 2010;25:745–9.

    Article  PubMed  CAS  Google Scholar 

  77. Alvarado-Esquivel C, Carrera-Gracia MA, Conde-González CJ, et al. Genotypic resistance to lamivudine among hepatitis B virus isolates in Mexico. J Antimicrob Chemother. 2006;57:221–3.

    Article  PubMed  CAS  Google Scholar 

  78. Pol S, Sogni P. Treatment of chronic hepatitis B: adherence and safety. Gastroenterol Clin Biol. 2010;34(Supple 2):S142–8.

    Article  PubMed  Google Scholar 

  79. Chotiyaputta W, Peterson C, Ditah F, Goodwin D, Lok A. Persistence and adherence to nucleos(t)ide analogue treatment for chronic hepatitis B. J Hepatol. 2010;54:12–8.

    Article  PubMed  Google Scholar 

  80. Lok A, McMahon B. Chronic hepatitis B: update 2009. AASLD Practice Guidelines. Hepatology. 2009:1–36.

  81. Fung S, Chae HB, Fontana R. Virologic response and resistance to adefovir in patients with chronic hepatitis B. J Hepatol. 2006;43:283–90.

    Article  Google Scholar 

  82. Florian B, Mahnaz A, Francesco N. The new EASL guidelines for the management of chronic hepatitis B infection adapted for Swiss physicians. Swiss Med Wkly. 2010;140:154–9.

    Google Scholar 

  83. Hui CK, Zhang HY, Bowden S, Locarnini S, Luk JM, Leung KW, et al. 96 weeks combination of adefovir dipivoxil plus emtricitabine vs. adefovir dipivoxil monotherapy in the treatment of chronic hepatitis B. J Hepatol. 2008;48:714–20.

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

We would like to thank National Health and Medical Research Council of Australia for support of the Ph.D. scholarship for Dr Uma Devi.

Disclosure

No potential conflicts of interest relevant to this article were reported.

Author information

Authors and Affiliations

  1. Victorian Infectious Diseases Reference Laboratory, 10 Wreckyn St, North Melbourne, Victoria, 3051, Australia

    Uma Devi & Stephen Locarnini

  2. Infectious Diseases Unit, Eastern Health, Ringwood East, 3135, Victoria, Australia

    Uma Devi

Authors
  1. Uma Devi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Stephen Locarnini
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Uma Devi or Stephen Locarnini.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Devi, U., Locarnini, S. Role of Resistance Testing During Oral Antiviral Therapy of Chronic Hepatitis B. Curr Hepatitis Rep 11, 55–64 (2012). https://doi.org/10.1007/s11901-012-0132-8

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11901-012-0132-8

Keywords

Search

Navigation