Skip to main content

Advertisement

Log in

Role of combination therapy in chronic hepatitis B

  • Published:
Current Gastroenterology Reports Aims and scope Submit manuscript

Abstract

Combination therapy includes the use of two or more antivirals for the treatment of chronic hepatitis B. No study has shown that combination therapy is superior to monotherapy in naive patients for achieving treatment end points, but combination appears to result in a lower incidence of resistance. Moreover, the higher-potency compounds have not yet been studied. Consideration should be given to treating lamivudine-resistant patients with combination therapy, preferably with a nucleotide analogue in conjunction with a nucleoside analogue. Combination therapy should be considered in patients with decompensated cirrhosis who are unable to achieve an undetectable viral level on monotherapy and in naive patients who still have a detectable viral level 6 to 12 months after starting therapy.

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

Access this article

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

Instant access to the full article PDF.

Similar content being viewed by others

References and Recommended Reading

  1. Lee WM: Hepatitis B virus infection. N Engl J Med 1997, 337:1733–1744.

    Article  PubMed  CAS  Google Scholar 

  2. Lavanchy D: Hepatitis B virus epidemiology, disease burden, treatment, and current and emerging prevention and control measures. J Viral Hepat 2004, 11:97–107.

    Article  PubMed  CAS  Google Scholar 

  3. Beasley RP: Hepatitis B virus. The major etiology of hepatocellular carcinoma. Cancer 1988, 61:1942–1956.

    Article  PubMed  CAS  Google Scholar 

  4. Fung SK, Andreone P, Han SH, et al.: Adefovir-resistant hepatitis B can be associated with viral rebound and hepatic decompensation. J Hepatol 2005, 43:937–943.

    Article  PubMed  CAS  Google Scholar 

  5. Liaw Y-F, Sung JJY, Chow WC, et al.: Lamivudine for patients with chronic hepatitis B and advanced liver disease. N Engl J Med 2004, 351:1521–1531.

    Article  PubMed  CAS  Google Scholar 

  6. Keeffe EB, Dieterich DT, Han S-H, et al.: A treatment algorithm for the management of chronic hepatitis B virus infection in the United States: an update. Clin Gastroenterol Hepatol 2006, 4:936–962.

    Article  PubMed  CAS  Google Scholar 

  7. Lok AS, McMahon BJ: Chronic hepatitis B. Hepatology 2007, 45:507–537.

    Article  PubMed  CAS  Google Scholar 

  8. Hoofnagle JH, Doo E, Liang TJ, et al.: Management of hepatitis B: summary of a clinical research workshop. Hepatology 2007, 45:1056–1075.

    Article  PubMed  CAS  Google Scholar 

  9. Berenguer M, Wright TL: Treatment of recurrence of hepatitis B in transplant patients. J Hepatol 2003, 39(Suppl 1):S190–S193.

    Article  PubMed  CAS  Google Scholar 

  10. Thio CL, Locarnini S: Treatment of HIV/HBV coinfection: clinical and virologic issues. AIDS Rev 2007, 9:40–53.

    PubMed  Google Scholar 

  11. 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 

  12. Lau GKK, Piratvisuth T, Luo KX, et al.: Peginterferon alfa-2a, lamivudine, and the combination for HBeAg-positive chronic hepatitis B. N Engl J Med 2005, 352:2682–2695.

    Article  PubMed  CAS  Google Scholar 

  13. Chan HL, Leung NW, Hui AY, et al.: A randomized, controlled trial of combination therapy for chronic hepatitis B: comparing pegylated interferon-alpha2b and lamivudine with lamivudine alone. Ann Intern Med 2005, 142:240–250.

    PubMed  CAS  Google Scholar 

  14. Janssen HLA, van Zonneveld M, Senturk H, et al.: Pegylated interferon alfa-2b alone or in combination with lamivudine for HBeAg-positive chronic hepatitis B: a randomised trial. Lancet 2005, 365:123–129.

    Article  PubMed  CAS  Google Scholar 

  15. Marcellin P, Lau GKK, Bonino F, et al.: Peginterferon alfa-2a alone, lamivudine alone, and the two in combination in patients with HBeAg-negative chronic hepatitis B. N Engl J Med 2004, 351:1206–1217.

    Article  PubMed  CAS  Google Scholar 

  16. Marcellin P, Piratvisuth T, Brunetto M, et al.: Virological and biochemical response in patients with HBeAg-negative chronic hepatitis B treated with peg-interferon alfa-2a (40KD) with or without lamivudine: results of 4 year follow-up [abstract 103]. J Hepatol 2008, 48(Suppl 2):S46.

    Article  Google Scholar 

  17. 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, 129:528–536.

    PubMed  CAS  Google Scholar 

  18. Sung JJ, Lai JY, Zeuzem S, et al.: Lamivudine compared with lamivudine and adefovir dipivoxil for the treatment of HBeAg-positive chronic hepatitis B. J Hepatol 2008, 48:728–735.

    Article  PubMed  CAS  Google Scholar 

  19. Hui CK, Zhang HY, Bowden S, et al.: 96 weeks combination of adefovir dipivoxil plus emtricitabine vs. adefovir dipivoxil monotherapy in the treatment of chronic hepatitis B. J Hepatol 2008, 48:714–720.

    Article  PubMed  CAS  Google Scholar 

  20. Keeffe EB, Zeuzem S, Koff RS, et al.: Report of an international workshop: roadmap for management of patients receiving oral therapy for chronic hepatitis B. Clin Gastroenterol Hepatol 2007, 5:890–897.

    Article  PubMed  Google Scholar 

  21. Peters MG, Hann HWH, Martin P, et al.: Adefovir dipivoxil alone or in combination with lamivudine in patients with lamivudine-resistant chronic hepatitis B. Gastroenterology 2004, 126:91–101.

    Article  PubMed  CAS  Google Scholar 

  22. Perrillo R, Hann H-W, Mutimer D, et al.: Adefovir dipivoxil added to ongoing lamivudine in chronic hepatitis B with YMDD mutant hepatitis B virus. Gastroenterology 2004, 126:81–90.

    Article  PubMed  CAS  Google Scholar 

  23. Rapti I, Dimou F, Mitsoula P, Hadziyannis SJ: Adding-on versus switching-to adefovir therapy in lamivudine-resistant HBeAg-negative chronic hepatitis B. Hepatology 2007, 45:307–313.

    Article  PubMed  CAS  Google Scholar 

  24. Fung SK, Chae HB, Fontana RJ, et al.: Virologic response and resistance to adefovir in patients with chronic hepatitis B. J Hepatol 2006, 44:283–290.

    Article  PubMed  CAS  Google Scholar 

  25. 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, 43:1385–1391.

    Article  PubMed  CAS  Google Scholar 

  26. Lampertico P, Marzano A, Levrero M, et al.: Adefovir and lamivudine combination therapy is superior to adefovir monotherapy for lamivudine-resistant patients with HBeAg-negative chronic hepatitis B [abstract LB5]. Hepatology 2006, 44(Suppl 1):693A.

    Google Scholar 

  27. Lampertico P, Vigano M, Manenti E, et al.: Adefovir rapidly suppresses hepatitis B in HBeAg-negative patients developing genotypic resistance to lamivudine. Hepatology 2005, 42:1414–1419.

    Article  PubMed  CAS  Google Scholar 

  28. Lampertico P, Vigano M, Manenti E, et al.: Low resistance to adefovir combined with lamivudine: a 3-year study of 145 lamivudine-resistant hepatitis B patients. Gastroenterology 2007, 133:1445–1451.

    Article  PubMed  CAS  Google Scholar 

  29. van Bömmel F, Zöllner B, Sarrazin C, et al.: Tenofovir for patients with lamivudine-resistant hepatitis B virus (HBV) infection and high HBV DNA level during adefovir therapy. Hepatology 2006, 44:318–325.

    Article  PubMed  CAS  Google Scholar 

  30. Lim SG: Randomized, double-blind study of emtricitabine (FTC) plus clevudine versus FTC alone in treatment of chronic hepatitis B. Antimicrob Agents Chemother 2006, 50:1642–1648.

    Article  PubMed  CAS  Google Scholar 

  31. Santos SA, Uriel AJ, Park JS, et al.: Effect of switching to tenofovir with emtricitabine in patients with chronic hepatitis B failing to respond to an adefovir-containing regimen. Eur J Gastroenterol Hepatol 2006, 18:1247–1253.

    Article  PubMed  CAS  Google Scholar 

  32. Tan J, Degertekin B, Wong SN, et al.: Tenofovir monotherapy is effective in hepatitis B patients with antiviral treatment failure to adefovir in the absence of adefovir-resistant mutations. J Hepatol 2008, 48:383–386.

    Article  CAS  Google Scholar 

  33. Berg T, Moller B, Trinh H, et al.: Tenofovir disoproxil fumarate (TDF) versus emtricitabine plus TDF for treatment of chronic hepatitis B (CHB) in subjects with persistent viral replication receiving adefovir dipivoxil (ADV) [abstract 76]. Presented at the 43rd Annual Meeting of the European Association for the Study of the Liver. Milan, Italy; April 23–27, 2008.

  34. Leemans WF, Niesters HGM, van der Eijk AA, et al.: Selection of an entecavir-resistant mutant despite prolonged hepatitis B virus DNA suppression, in a chronic hepatitis B patient with preexistent lamivudine resistance: successful rescue therapy with tenofovir. Eur J Gastroenterol Hepatol 2008, 20:773–777.

    Article  PubMed  CAS  Google Scholar 

  35. Chang T-T, Gish RG, De Man RA, et al.: A comparison of entecavir and lamivudine for HBeAg-positive chronic hepatitis B. N Engl J Med 2006, 354:1001–1010.

    Article  PubMed  CAS  Google Scholar 

  36. Marcellin P, Chang T-T, Lim SG, et al.: Adefovir dipivoxil for the treatment of hepatitis B e antigen-positive chronic hepatitis B. N Engl J Med 2003, 348:808–816.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to John D. Scott.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Scott, J.D., McMahon, B. Role of combination therapy in chronic hepatitis B. Curr Gastroenterol Rep 11, 28–36 (2009). https://doi.org/10.1007/s11894-009-0005-7

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11894-009-0005-7

Keywords

Navigation