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Figure 15 depicts the percentage of individuals achieving HBV DNA suppression to a level <20,000 copies/mL at the end of followup. Again, both groups receiving interferon fared better than the lamivudine monotherapy group, with no difference between the two interferon-containing regimens.14
FIGURE 15
Reminiscent of the study in HBeAg-positive patients, there was a greater decline of serum HBV DNA in the combination therapy group than in either of the monotherapy groups (Fig. 16).14 Lamivudine monotherapy initially seemed to cause more rapid HBV DNA decline compared to interferon monotherapy; however, the difference between the two monotherapies was no longer evident at the end of treatment, possibly due to emergence of lamivudine-resistant mutants in the lamivudine monotherapy limb. In this study, the end-of-treatment difference in viral suppression was on the order of 1 log greater with combination therapy (in contrast to the 3-log difference seen in the study of HBeAg-positive patients).
FIGURE 16
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Summary
Pegylated interferon appears to be more potent than conventional interferon in the treatment of chronic hepatitis B. Combined use with nucleoside analogue therapy is associated with greater viral suppression than either agent given alone; however, sustained virologic responses have not been shown to occur any more frequently with combination therapy than with either agent alone. Future studies should address ways of maximizing sustained virologic response. Consideration should probably be given to higher and more consistent interferon dosing and possibly to altering the way in which the two drugs are combined. Theoretically, simultaneous administration of the two drugs might abrogate the immunologic response to interferon; therefore, it is possible that a lead-in phase with pegylated interferon followed by nucleoside analogue therapy might be more effective than giving the two drugs simultaneously. Finally, different dosage recommendations should be investigated for patients with unfavorable viral genotypes.
The take-home message is that interferons and nucleoside analogues work through different mechanisms of action. Although two large-scale trials have failed to show sustained differences between combination therapy and interferon monotherapy, further research is needed before discounting the possibility that combined therapy may lead to a higher rate of more lasting response.
References
- Perrillo RP. Overview of treatment of hepatitis B: key approaches and clinical challenges. Semin Liver Dis. 2004;24 Suppl 1:23-9.
- Keeffe EB, Dieterich DT, Han SH, et al. A treatment algorithm for the management of chronic hepatitis B virus infection in the United States. Clin Gastroenterol Hepatol. 2004 Feb;2(2):87-106.
- Lau DT, Everhart J, Kleiner DE, et al. Long-term follow-up of patients with chronic hepatitis B treated with interferon alfa. Gastroenterology. 1997 Nov;113(5):1660-7.
- Shiffman M, Marcellin P, Jeffers L, et al. HBsAg seroconversion in adefovir dipivoxil (ADV) treated chronic hepatitis B (CHB) patients. J Hepatol. 2004;40 (Suppl 1): 17. Abstract 45.
- Janssen HL, Gerken G, Carreno V, et al. Interferon alfa for chronic hepatitis B infection: increased efficacy of prolonged treatment. The European Concerted Action on Viral Hepatitis (EUROHEP). Hepatology. 1999 Jul;30(1):238-43.
- Carreno V, Marcellin P, Hadziyannis S, et al. Retreatment of chronic hepatitis B e antigen- positive patients with recombinant interferon alfa-2a. The European Concerted Action on Viral Hepatitis (EUROHEP). Hepatology. 1999 Jul;30(1):277-82.
- Perrillo RP, Schiff ER, Davis GL, et al. A randomized, controlled trial of interferon alfa-2b alone and after prednisone withdrawal for the treatment of chronic hepatitis B. The Hepatitis Interventional Therapy Group. N Engl J Med. 1990 Aug 2;323(5):295-301.
- Thomas HC, Karayiannis P, Brook G. Treatment of hepatitis B virus infection with interferon. Factors predicting response to interferon. J Hepatol. 1991;13 Suppl 1:S4-7.
- Nair S, Perrillo RP. Serum alanine aminotransferase flares during interferon treatment of chronic hepatitis B: is sustained clearance of HBV DNA dependent on levels of pretreatment viremia? Hepatology. 2001 Nov;34(5):1021-6.
- Cooksley WG, Piratvisuth T, Lee SD, et al. Peginterferon alpha-2a (40 kDa): an advance in the treatment of hepatitis B e antigen-positive chronic hepatitis B. J Viral Hepat. 2003 Jul;10(4):298- 305.
- 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 Apr;46(4):562-8.
- Schiff ER, Dienstag JL, Karayalcin S, et al. Lamivudine and 24 weeks of lamivudine/interferon combination therapy for hepatitis B e antigen-positive chronic hepatitis B in interferon nonresponders. J Hepatol. 2003 Jun;38(6):853-5.
- Janssen HLA, Senturk H, Zeuzem S, et al. Pegylated interferon a-2b alone or in combination with lamivudine as treatment for HBeAg-positive chronic hepatitis B. Lancet (in press).
- Marcellin P, Lau GK, 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 Sep16;351(12):1206-17.
http://www.meds.com/hepatitis/casebased/perrillo.html
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