Skip to main content

Advertisement

SpringerLink
Log in

Current options for the therapy of chronic hepatitis B infection

  • Published:
Current Infectious Disease Reports Aims and scope Submit manuscript

Abstract

Until recently the only available treatment for chronic hepatitis B was interferon-α. Over the past few years a new class of antiviral has become available, the reverse transcriptase inhibitors. Lamivudine is a nucleoside analogue reverse transcriptase inhibitor that was recently approved in many countries for the treatment of hepatitis B. Despite the potent action of lamivudine, the development of new antivirals and new strategies to treat hepatitis B are still the major goal. We review the latest options for therapy of chronic hepatitis B, including combination strategies that could be an approach to improving the response rate of antivirals.

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

Similar content being viewed by others

References and Recommended Reading

  1. Omata M: Treatment of chronic hepatitis B infection. N Engl J Med 1998, 339:114–115.

    Article  PubMed  CAS  Google Scholar 

  2. Lai CL, Chien RN, Leung NW, et al.: A one-year trial of lamivudine for chronic hepatitis B. Asia Hepatitis Lamivudine Study Group. N Engl J Med 1998, 339:61–68.

    Article  PubMed  CAS  Google Scholar 

  3. Boni C, Bertoletti A, Penna A, et al.: Lamivudine treatment can restore T cell responsiveness in chronic hepatitis B. J Clin Invest 1998, 102:968–975. This study found that the T-cell response can be restored by lamivudine treatment. Interesting discussion concerning the best strategy to combine lamivudine and interferon sequentially, rather than simultaneously.

    Article  PubMed  CAS  Google Scholar 

  4. Chien RN, Liaw YF, Atkins M: Pretherapy alanine transaminase level as a determinant for hepatitis B e antigen seroconversion during lamivudine therapy in patients with chronic hepatitis B. Asian Hepatitis Lamivudine Trial Group. Hepatology 1999, 30:770–774.

    Article  PubMed  CAS  Google Scholar 

  5. Lai CL: Antiviral therapy for hepatitis B and C in Asians. J Gastroenterol Hepatol 1999, 14(suppl):S19-S21.

    PubMed  Google Scholar 

  6. Liaw YF, Leung NW, Chang TT, et al.: Effects of extended lamivudine therapy in Asian patients with chronic hepatitis B. Asia Hepatitis Lamivudine Study Group. Gastroenterology 2000, 119:172–180. This report describes the second year results of the Asian multicenter study of lamivudine treatment.

    Article  PubMed  CAS  Google Scholar 

  7. Nowak MA, Bonhoeffer S, Hill AM, et al.: Viral dynamics in hepatitis B virus infection. Proc Natl Acad Sci U S A, 1996, 93:4398–4402.

    Article  PubMed  CAS  Google Scholar 

  8. Lau DT-Y, Khokhar MF, Ghany MG, et al.: Long-term lamivudine therapy for chronic hepatitis B. Antiviral Ther 2000, 5(suppl 1):43.

    Google Scholar 

  9. Dienstag JL, Schiff ER, Wright TL, et al.: Lamivudine as initial treatment for chronic hepatitis B in the United States. N Engl J Med 1999, 341(17):1256–1263.

    Article  PubMed  CAS  Google Scholar 

  10. Leung N: Liver disease-significant improvement with lamivudine. J Med Virol 2000, 61:380–385.

    Article  PubMed  CAS  Google Scholar 

  11. Ben-Ari Z, Pappo O, Zemel R, et al.: Association of lamivudine resistance in recurrent hepatitis B after liver transplantation with advanced hepatic fibrosis. Transplantation 1999, 68:232–236.

    Article  PubMed  CAS  Google Scholar 

  12. Bessesen M, Ives D, Condreay L, et al.: Chronic active hepatitis B exacerbations in human immunodeficiency virus-infected patients following development of resistance to or withdrawal of lamivudine. Clin Infect Dis 1999, 28:1032–1035.

    Article  PubMed  CAS  Google Scholar 

  13. De Castro LM, Kern ER, De Clercq E, et al.: Phosphonylmethoxyalkyl purine and pyrimidine derivatives for treatment of opportunistic cytomegalovirus and herpes simplex virus infections in murine AIDS. Antiviral Res 1991, 16:101–114.

    Article  PubMed  Google Scholar 

  14. Deeks SG, Collier A, Lalezari J, et al.: The safety and efficacy of adefovir dipivoxil, a novel anti-human immunodeficiency virus (HIV) therapy, in HIV-infected adults: a randomized, double-blind, placebo-controlled trial. J Infect Dis 1997, 176:1517–1523.

    Article  PubMed  CAS  Google Scholar 

  15. Gilson RJ, Chopra KB, Newell AM, et al.: A placebo-controlled phase I/II study of adefovir dipivoxil in patients with chronic hepatitis B virus infection. J Viral Hepat 1999, 6:387–395.

    Article  PubMed  CAS  Google Scholar 

  16. Ono-Nita SK, Kato N, Shiratori Y, et al.: Susceptibility of lamivudine-resistant hepatitis B virus to other reverse transcriptase inhibitors. J Clin Invest 1999, 103(12):1635–1640.

    Article  PubMed  CAS  Google Scholar 

  17. Xiong X, Flores C, Yang H, et al.: Mutations in hepatitis B DNA polymerase associated with resistance to lamivudine do not confer resistance to adefovir in vitro. Hepatology 1998, 28:1669–1673.

    Article  PubMed  CAS  Google Scholar 

  18. Perrillo R, Schiff E, Yoshida E, et al.: Adefovir dipivoxil for the treatment of lamivudine-resistant hepatitis B mutants. Hepatology 2000, 32:129–134. This study reports on a treatment option for lamivudine-resistant HBV.

    Article  PubMed  CAS  Google Scholar 

  19. Kahn J, Lagakos S, Wulfsohn M, et al.: Efficacy and safety of adefovir dipivoxil with antiretroviral therapy: a randomized controlled trial. JAMA 1999, 282(24):2305–2312.

    Article  PubMed  CAS  Google Scholar 

  20. Jeffers L, Heathcote E, Wright T, et al.: A phase II dose-ranging, placebo-controled trial of adefovir dipivoxil for the treatment of chronic hepatitis B virus infection [abstract]. Antiviral Res 1998, 37:A197.

    Google Scholar 

  21. Boyd MR, Safrin S, Kern ER: Penciclovir: a review of its spectrum of activity, selectivity, and cross-resistance pattern. Antiviral Chem Chemother 1993, 4(suppl 1):3–11.

    CAS  Google Scholar 

  22. Bacon TH: Famciclovir, from the bench to the patient - a comprehensive review of preclinical data. Int J Antimicrob Agents 1996, 7:119–134.

    Article  PubMed  CAS  Google Scholar 

  23. Boker KH, Ringe B, Kruger M, et al.: Prostaglandin E plus famciclovir--a new concept for the treatment of severe hepatitis B after liver transplantation. Transplantation 1994, 57(12):1706–1708.

    PubMed  CAS  Google Scholar 

  24. Klein M, Geoghegan J, Schmidt K, et al.: Conversion of recurrent delta-positive hepatitis B infection to seronegativity with famciclovir after liver transplantation. Transplantation 1997, 64:162–163.

    Article  PubMed  CAS  Google Scholar 

  25. Aye TT, Bartholomeusz A, Shaw T, et al.: Hepatitis B virus polymerase mutations during antiviral therapy in a patient following liver transplantation. J Hepatol 1997, 26:1148–1153.

    Article  PubMed  CAS  Google Scholar 

  26. Singh N, Gayowski T, Wannstedt CF, et al.: Pretransplant famciclovir as prophylaxis for hepatitis B virus recurrence after liver transplantation. Transplantation 1997, 63(10):1415–1419.

    Article  PubMed  CAS  Google Scholar 

  27. de Man RA, Marcellin P, Habal F, et al.: A randomized, placebo-controlled study to evaluate the efficacy of 12-month famciclovir treatment in patients with chronic hepatitis B e antigen-positive hepatitis B. Hepatology 2000, 32:413–417.

    Article  PubMed  Google Scholar 

  28. Genovesi EV, Lamb L, Medina I, et al.: Efficacy of the carbocyclic 2′-deoxyguanosine nucleoside BMS-200475 in the woodchuck model of hepatitis B virus infection. Antimicrob Agents Chemother 1998, 42(12):3209–3217.

    PubMed  CAS  Google Scholar 

  29. Colonno RJ: Identification of BMS-200475 as a novel and potent inhibitor of hepatitis B replication. Accessible at www.thebody.com/anti497/bms.html.

  30. Balakrishna Pai S, Liu SH, Zhu YL, et al.: Inhibition of hepatitis B virus by a novel L-nucleoside, 2′-fluoro-5-methyl-beta-Larabinofuranosyl uracil. Antimicrob Agents Chemother 1996, 40:380–386.

    PubMed  CAS  Google Scholar 

  31. Aguesse-Germon S, Liu SH, Chevallier M, et al.: Inhibitory effect of 2′-fluoro-5-methyl-beta-L-arabinofuranosyl-uracil on duck hepatitis B virus replication. Antimicrob Agents Chemother 1998, 42:369–376.

    PubMed  CAS  Google Scholar 

  32. Jansen RW, Johnson LC, Averett DR: High-capacity in vitro assessment of anti-hepatitis B virus compound selectivity by a virion-specific polymerase chain reaction assay. Antimicrob Agents Chemother 1993, 37:441–447.

    PubMed  CAS  Google Scholar 

  33. Cullen JM, Smith SL, Davis MG, et al.: In vivo antiviral activityand pharmacokinetics of (-)-cis-5-fluoro-1-[2-(hydroxymethyl)-1,3-oxathiolan-5-yl]cytosine in woodchuck hepatitis virus-infected woodchucks. Antimicrob Agents Chemother 1997, 41(10):2076–2082.

    PubMed  CAS  Google Scholar 

  34. Wong DK, Cheung AM, O’Rourke K, et al.: Effect of alpha-interferon treatment in patients with hepatitis B e antigen-positive chronic hepatitis B. A meta-analysis. Ann Intern Med 1993, 119:312–323.

    PubMed  CAS  Google Scholar 

  35. Lin SM, Sheen IS, Chien RN, et al.: Long-term beneficial effect of interferon therapy in patients with chronic hepatitis B virus infection. Hepatology 1999, 29:971–975. This study describes the long follow-up of chronic hepatitis B patients treated with interferon.

    Article  PubMed  CAS  Google Scholar 

  36. Mutchnick MG, Appelman HD, Chung HT, et al.: Thymosin treatment of chronic hepatitis B: a placebo-controlled pilot trial. Hepatology 1991, 14:409–415.

    Article  PubMed  CAS  Google Scholar 

  37. Chien RN, Liaw YF, Chen TC, et al.: Efficacy of thymosin alpha1 in patients with chronic hepatitis B: a randomized, controlled trial. Hepatology 1998, 27:1383–1387.

    Article  PubMed  CAS  Google Scholar 

  38. Korba BE: In vitro evaluation of combination therapies against hepatitis B virus replication. Antiviral Res 1996, 29:49–51.

    Article  PubMed  CAS  Google Scholar 

  39. Colledge D, Locarnini S, Shaw T: Synergistic inhibition of hepadnaviral replication by lamivudine in combination with penciclovir in vitro. Hepatology 1997, 26:216–225.

    PubMed  CAS  Google Scholar 

  40. Colledge D, Civitico G, Locarnini S, Shaw T: In vitro antihepadnaviral activities of combinations of penciclovir, lamivudine, and adefovir. Antimicrob Agents Chemother 2000, 44:551–560. This study describes the in vitro results of the combination of the three reverse transcriptase inhibitors that are already in clinical trials.

    Article  PubMed  CAS  Google Scholar 

  41. Lau GK, Tsiang M, Hou J, et al.: Combination therapy with lamivudine and famciclovir for chronic hepatitis B-infected Chinese patients: a viral dynamics study. Hepatology 2000, 32:394–399.

    Article  PubMed  CAS  Google Scholar 

  42. Schalm SW, Heathcote J, Cianciara J, et al.: Lamivudine and alpha interferon combination treatment of patients with chronic hepatitis B infection: a randomised trial. Gut 2000, 46:562–568.

    Article  PubMed  CAS  Google Scholar 

  43. Marinos G, Naoumov NV, Williams R: Impact of complete inhibition of viral replication on the cellular immune response in chronic hepatitis B virus infection. Hepatology 1996, 24:991–995.

    Article  PubMed  CAS  Google Scholar 

  44. Tur-Kaspa R, Burk RD, Shaul Y, Shafritz DA: Hepatitis B virus DNA contains a glucocorticoid-responsive element. Proc Natl Acad Sci U S A 1986, 83:1627–1631.

    Article  PubMed  CAS  Google Scholar 

  45. Lok AS, Wu PC, Lai CL, et al.: A controlled trial of interferon with or without prednisone priming for chronic hepatitis B. Gastroenterology 1992, 102:2091–2097.

    PubMed  CAS  Google Scholar 

  46. Liaw YF, Tsai SL, Chien RN, et al.: Prednisolone priming enhances Th1 response and efficacy of subsequent lamivudine therapy in patients with chronic hepatitis B. Hepatology 2000, 32:604–609.

    Article  PubMed  CAS  Google Scholar 

  47. Laskus T, Radkowski M, Slusarczyk J, Cianciara J: Severe exacerbation of chronic active hepatitis B during interferon alpha therapy. Digestion 1992, 52:61–64.

    Article  PubMed  CAS  Google Scholar 

  48. Perrillo RP, Schiff ER, Davis G, et al.: A randomized, controlled trial of interferon alfa-2b alone and after prednisone withdrawal for the treatment of chronic hepatitis B. N Engl J Med 1990, 323:295–301.

    Article  PubMed  CAS  Google Scholar 

  49. Lai C-L, Chien R-N, Leung N, et al.: A one-year trial of lamivudine for chronic hepatitis B. N Engl J Med 1998, 339:61–68.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Gastroenterology, Faculty of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, 113-8655, Tokyo, Japan

    Suzane Kioko Ono-Nita MD, PhD, Naoya Kato MD, Yasushi Shiratori MD & Masao Omata MD

Authors
  1. Suzane Kioko Ono-Nita MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Naoya Kato MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yasushi Shiratori MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Masao Omata MD
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ono-Nita, S.K., Kato, N., Shiratori, Y. et al. Current options for the therapy of chronic hepatitis B infection. Curr Infect Dis Rep 3, 137–142 (2001). https://doi.org/10.1007/s11908-996-0036-2

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11908-996-0036-2

Keywords

Search

Navigation