Skip to main content

Advertisement

SpringerLink
Log in

Interferon and nucleoside analog combination therapy for hepatitis B

  • Clinical Review
  • Published:
Clinical Journal of Gastroenterology Aims and scope Submit manuscript

Abstract

Interferon therapy has several advantages over nucleoside or nucleotide analog therapy: finite duration, durable treatment response, and no viral resistance. However, it is only effective in about 30% of patients. To improve its efficacy, the combination of interferon and nucleoside/nucleotide analogs may facilitate additive or synergistic effects. This is because interferon and nucleoside/nucleotide analogs have different mechanisms of action. Recent studies demonstrate that concomitant use of lamivudine and peginterferon does not improve biochemical and virological responses compared with peginterferon monotherapy. By contrast, sequential or staggered administration of lamivudine and interferon appears to have some benefits over monotherapies. There is a paucity of data on interferon combined with drugs other than lamivudine, such as adefovir and entecavir. Although combination therapies have the potential to improve efficacy against hepatitis-B virus, it is unclear how interferon should be combined with other drugs or which patients should be treated with combination therapies.

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

  1. Liaw YF, Leung NW, Chang TT, Guan R, Tai DI, Ng KY, et al. Effects of extended lamivudine therapy in Asian patients with chronic hepatitis B. Gastroenterology. 2000;119:172–80.

    Article  CAS  PubMed  Google Scholar 

  2. Yao GB, Cui ZY, Wang BE, Yao JL, Zeng MD. A 3-year clinical trial of lamivudine in treatment of patients with chronic hepatitis B. Hepatobiliary Pancreat Dis Int. 2004;3:188–93.

    CAS  PubMed  Google Scholar 

  3. Chang TT, Lai CL, Chien RN, Guan R, Lim SG, Lee CM, et al. Four years of lamivudine treatment in Chinese patients with chronic hepatitis B. J Gastroenterol Hepatol. 2004;19:1276–82.

    Article  CAS  PubMed  Google Scholar 

  4. Lok AS, Lai CL, Leung N, Yao GB, Cui ZY, Schiff ER, et al. Long-term safety of lamivudine treatment in patients with chronic hepatitis B. Gastroenterology. 2003;125:1714–22.

    Article  CAS  PubMed  Google Scholar 

  5. Fontana RJ. Side effects of long-term oral antiviral therapy for hepatitis B. Hepatology. 2009;49:S185–95.

    Article  CAS  PubMed  Google Scholar 

  6. Seok JI, Lee DK, Lee CH, Park MS, Kim SY, Kim HS, et al. Long-term therapy with clevudine for chronic hepatitis B can be associated with myopathy characterized by depletion of mitochondrial DNA. Hepatology. 2009;49:2080–6.

    Article  CAS  PubMed  Google Scholar 

  7. van Nunen AB, Hansen BE, Suh DJ, Lohr HF, Chemello L, Fontaine H, et al. Durability of HBeAg seroconversion following antiviral therapy for chronic hepatitis B: relation to type of therapy and pretreatment serum hepatitis B virus DNA and alanine aminotransferase. Gut. 2003;52:420–4.

    Article  PubMed  Google Scholar 

  8. European Association for the Study of the Liver. EASL clinical practice guidelines: management of chronic hepatitis B. J Hepatol. 2009;50:227–42.

    Article  CAS  PubMed  Google Scholar 

  9. Lok ASF, McMahon BJ. Chronic hepatitis B. Hepatology. 2007;45:507–39.

    Article  CAS  PubMed  Google Scholar 

  10. Buster EH, Hansen BE, Lau GK, Piratvisuth T, Zeuzem S, Steyerberg EW, et al. Factors that predict response of patients with hepatitis B e antigen-positive chronic hepatitis B to peginterferon-alpha. Gastroenterology. 2009;137:2002–9.

    Article  CAS  PubMed  Google Scholar 

  11. Okanoue T, Minami M. Update of research and management of hepatitis B. J Gastroenterol. 2006;41:107–8.

    Article  PubMed  Google Scholar 

  12. Barbaro G, Zechini F, Pellicelli AM, Francavilla R, Scotto G, Bacca D, et al. Long-term efficacy of interferon alpha-2b and lamivudine in combination compared to lamivudine monotherapy in patients with chronic hepatitis B. J Hepatol. 2001;35:406–11.

    Article  CAS  PubMed  Google Scholar 

  13. Santantonio T, Niro GA, Sinisi E, Leandro G, Insalata M, Guastadisegni A, et al. Lamivudine/interferon combination therapy in anti-HBe positive chronic hepatitis B patients: a controlled pilot study. J Hepatol. 2002;36:799–804.

    Article  CAS  PubMed  Google Scholar 

  14. Yalcin K, Degertekin H, Yildiz F, Celik Y. Comparison of 12-month courses of interferon-alpha-2b-lamivudine combination therapy and interferon-alpha-2b monotherapy among patients with untreated chronic hepatitis B. Clin Infect Dis. 2003;36:1516–22.

    Article  CAS  PubMed  Google Scholar 

  15. Economou M, Manolakopoulos S, Trikalinos TA, Filis S, Bethanis S, Tzourmakliotis D, et al. Interferon-alpha plus lamivudine vs. lamivudine reduces breakthroughs, but does not affect sustained response in HBeAg negative chronic hepatitis B. World J Gastroenterol. 2005;11:5882–7.

    CAS  PubMed  Google Scholar 

  16. Marcellin P, Lau GK, Bonino F, Farci P, Hadziyannis S, Jin R, 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;351:1206–17.

    Article  CAS  PubMed  Google Scholar 

  17. Janssen HL, van Zonneveld M, Senturk H, Zeuzem S, Akarca US, Cakaloglu Y, et al. Pegylated interferon alfa-2b alone or in combination with lamivudine for HBeAg-positive chronic hepatitis B: a randomised trial. Lancet. 2005;365:123–9.

    Article  CAS  PubMed  Google Scholar 

  18. Lau GK, Piratvisuth T, Luo KX, Marcellin P, Thongsawat S, Cooksley G, et al. Peginterferon Alfa-2a, lamivudine, and the combination for HBeAg-positive chronic hepatitis B. N Engl J Med. 2005;352:2682–95.

    Article  CAS  PubMed  Google Scholar 

  19. Ayaz C, Celen MK, Colak H, Hosoglu S, Geyik MF. Comparison of lamivudine and alpha-interferon combination with alpha-interferon alone in the treatment of HBeAg-positive chronic hepatitis B. Indian J Gastroenterol. 2006;25:71–3.

    PubMed  Google Scholar 

  20. Kaymakoglu S, Oguz D, Gur G, Gurel S, Tankurt E, Ersöz G, et al. Pegylated interferon Alfa-2b monotherapy and pegylated interferon Alfa-2b plus lamivudine combination therapy for patients with hepatitis B virus e antigen-negative chronic hepatitis B. Antimicrob Agents Chemother. 2007;51:3020–2.

    Article  CAS  PubMed  Google Scholar 

  21. Papadopoulos VP, Chrysagis DN, Protopapas AN, Goulis IG, Dimitriadis GT, Mimidis KP. Peginterferon alfa-2b as monotherapy or in combination with lamivudine in patients with HBeAg-negative chronic hepatitis B: a randomised study. Med Sci Monit. 2009;15:CR56–61.

    CAS  PubMed  Google Scholar 

  22. Serfaty L, Thabut D, Zoulim F, Andreani T, Chazouillères O, Carbonell N, et al. Sequential treatment with lamivudine and interferon monotherapies in patients with chronic hepatitis B not responding to interferon alone: results of a pilot study. Hepatology. 2001;34:573–7.

    Article  CAS  PubMed  Google Scholar 

  23. Manesis EK, Papatheodoridis GV, Hadziyannis SJ. A partially overlapping treatment course with lamivudine and interferon in hepatitis B e antigen-negative chronic hepatitis B. Aliment Pharmacol Ther. 2006;23:99–106.

    Article  CAS  PubMed  Google Scholar 

  24. Shi M, Wang RS, Zhang H, Zhu YF, Han B, Zhang Y, et al. Sequential treatment with lamivudine and interferon-alpha monotherapies in hepatitis B e antigen-negative Chinese patients and its suppression of lamivudine-resistant mutations. J Antimicrob Chemother. 2006;58:1031–5.

    Article  CAS  PubMed  Google Scholar 

  25. Sarin SK, Sood A, Kumar M, Arora A, Amrapurkar D, Sharma BC, et al. Effect of lowering HBV DNA levels by initial antiviral therapy before adding immunomodulator on treatment of chronic hepatitis B. Am J Gastroenterol. 2007;102:96–104.

    Article  CAS  PubMed  Google Scholar 

  26. Boni C, Penna A, Ogg GS, Bertoletti A, Pilli M, Cavallo C, et al. Lamivudine treatment can overcome cytotoxic T-cell hyporesponsiveness in chronic hepatitis B: new perspectives for immune therapy. Hepatology. 2001;33:963–71.

    Article  CAS  PubMed  Google Scholar 

  27. Boni C, Penna A, Bertoletti A, Lamonaca V, Rapti I, Missale G, et al. Transient restoration of anti-viral T cell responses induced by lamivudine therapy in chronic hepatitis B. J Hepatol. 2003;39:595–605.

    Article  CAS  PubMed  Google Scholar 

  28. Minami M, Okanoue T. Management of HBV infection in Japan. Hepatol Res. 2007;37:S79–82.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Hirokoji, Kawaramachi, Kamigyo-ku, Kyoto, 602-8566, Japan

    Masahito Minami, Takayuki Katayama, Rei Sendo & Toshikazu Yoshikawa

  2. Department of Hepatology, Saiseikai Suita Hospital, 1-2 Kawazono-cho, Suita, Osaka, 564-0013, Japan

    Takeshi Okanoue

Authors
  1. Masahito Minami
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Takayuki Katayama
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Rei Sendo
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Takeshi Okanoue
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Toshikazu Yoshikawa
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Masahito Minami.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Minami, M., Katayama, T., Sendo, R. et al. Interferon and nucleoside analog combination therapy for hepatitis B. Clin J Gastroenterol 3, 69–72 (2010). https://doi.org/10.1007/s12328-010-0135-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12328-010-0135-3

Keywords

Search

Navigation