Gastroenterology
Volume 133, Issue 5 , Pages 1437-1444 , November 2007

Entecavir Therapy for up to 96 Weeks in Patients With HBeAg-Positive Chronic Hepatitis B

Presented in part at the 56th annual meeting of the American Association for the Study of Liver Diseases, November 11–15, 2005.

  • Robert G. Gish

      Affiliations

    • Division of Hepatology and Complex GI, California Pacific Medical Center, San Francisco, California
    • Corresponding Author InformationAddress requests for reprints to: Robert G. Gish, MD, Division of Hepatology and Complex GI, California Pacific Medical Center, 2340 Clay Street, San Francisco, California 94115. fax: (415) 776-0292.
    • ,
  • Anna S. Lok

      Affiliations

    • Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan
    • ,
  • Ting–Tsung Chang

      Affiliations

    • Department of Internal Medicine, National Cheng Kung University Medical College, Tainan, Taiwan
    • ,
  • Robert A. de Man

      Affiliations

    • Department of Gastroenterology and Hepatology, Erasmus Medical Center, University Hospital Rotterdam, Rotterdam, The Netherlands
    • ,
  • Adrian Gadano

      Affiliations

    • Sección Hepatología, Hospital Italiano, Buenos Aires, Argentina
    • ,
  • José Sollano

      Affiliations

    • Section of Gastroenterology, University of Santo Tomas, Manila, Philippines
    • ,
  • Kwang–Hyub Han

      Affiliations

    • Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
    • ,
  • You–Chen Chao

      Affiliations

    • Department of Internal Medicine, Tri-Service General Hospital, Taipei, Taiwan
    • ,
  • Shou–Dong Lee

      Affiliations

    • Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
    • ,
  • Melissa Harris

      Affiliations

    • Bristol-Myers Squibb, Research and Development, Plainsboro, New Jersey
    • ,
  • Joanna Yang

      Affiliations

    • Bristol-Myers Squibb, Research and Development, Wallingford, Connecticut
    • ,
  • Richard Colonno

      Affiliations

    • Bristol-Myers Squibb, Research and Development, Wallingford, Connecticut
    • ,
  • Helena Brett–Smith

      Affiliations

    • Bristol-Myers Squibb, Research and Development, Wallingford, Connecticut

Received 25 May 2007 ,Accepted 26 July 2007.

References 

  1. Lai CL, Ratziu V, Yuen MF, Poynard T. Viral hepatitis B. Lancet. 2003;362:2089–2094
  2. Lok ASF, Heathcote EJ, Hoofnagle JH. Management of hepatitis B: 2000—summary of a workshop. Gastroenterology. 2001;120:1828–1853
  3. Lee WM. Hepatitis B virus infection. N Engl J Med. 1997;337:1733–1745
  4. Ganem D, Prince AM. Hepatitis B virus infection—natural history and clinical consequences. N Engl J Med. 2004;350:1118–1129
  5. Chen CJ, Yang HI, Su J, et al. Risk of hepatocellular carcinoma across a biological gradient of serum hepatitis B virus DNA level. JAMA. 2006;295:65–73
  6. Iloeje UH, Yang HI, Su J, et al. Predicting liver cirrhosis risk based on the level of circulating hepatitis B viral load. Gastroenterology. 2006;130:678–686
  7. Chen G, Lin WY, Shen FM, et al. Viral load as a predictor of mortality from hepatocellular carcinoma and chronic liver disease in chronic hepatitis B infection. J Hepatol. 2005;42(Suppl 2):173
  8. Yu MW, Yeh SH, Chen PJ, et al. Hepatitis B virus genotype and DNA level and hepatocellular carcinoma: a prospective study in men. J Natl Cancer Inst. 2005;97:265–272
  9. Conjeevaram HS, Lok ASF. Management of chronic hepatitis B. J Hepatol. 2003;38:S90–S103
  10. Lok ASF, McMahon BJ. Chronic hepatitis B. Hepatology. 2007;45:507–539
  11. Liaw YF, Leung N, Guan R, et al. Asian-Pacific consensus statement on the management of hepatitis B: a 2005 update. Liver Int. 2005;25:472–489
  12. Wright TL, Avunduk C, Dienstag JL, et al. Advancing patient care: integrating new data. Am J Gastroenterol. 2006;101(1 Suppl):S32–S39
  13. Dienstag JL, Goldin RD, Heathcote EJ, et al. Histological outcome during long-term lamivudine therapy. Gastroenterology. 2003;124:105–117
  14. Leung NWY, Lai CL, Chang TT, et al. Extended lamivudine treatment in patients with chronic hepatitis B enhances hepatitis B e antigen seroconversion rates: results after 3 years of therapy. Hepatology. 2001;33:1527–1532
  15. Mommeja-Marin H, Mondou E, Blum MR, et al. Serum HBV DNA as a marker of efficacy during therapy for CHB infection: analysis and review of the literature. Hepatology. 2003;37:1309–1319
  16. Liaw YF, 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
  17. Di Marco V, Lo Iacono O, Camma C, et al. The long-term course of chronic hepatitis B. Hepatology. 1999;30:257–264
  18. Yuen MF, Seto WK, Chow DHF, et al. Long-term beneficial outcome of Chinese asymptomatic patients with HBeAg-positive chronic hepatitis B on continuous lamivudine therapy: 7-year experience. Hepatology. 2005;42(Suppl 1):583A
  19. Van Zonnenveld M, Honkoop P, Hansen BE, et al. Long-term follow-up of alpha-interferon treatment of patients with chronic hepatitis B. Hepatology. 2004;39:804–810
  20. Ohata K, Hamasaki K, Toriyama K, et al. High viral load is a risk factor for hepatocellular carcinoma in patients with chronic hepatitis B virus infection. J Gastroenterol Hepatol. 2004;19:670–675
  21. Innaimo SF, Seifer M, Bisacchi GS, et al. Identification of BMS-200475 as a potent and selective inhibitor of hepatitis B virus. Antimicrob Agents Chemother. 1997;41:1444–1448
  22. Chang TT, 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
  23. Colonno RJ, Rose RE, Baldick CJ, et al. Entecavir resistance is rare in nucleoside naïve patients. Hepatology. 2006;44:1656–1665
  24. Tenney DJ, Levine SM, Rose RE, et al. Clinical emergence of entecavir-resistant hepatitis B virus requires additional substitutions in virus already resistant to lamivudine. Antimicrob Agents Chermother. 2004;48:3498–3507
  25. Dienstag JL, Cianciara J, Karayalcin S, et al. Durability of serologic response after lamivudine treatment of chronic hepatitis B. Hepatology. 2003;37:748–755
  26. Chang TT, Shiffman ML, Tong M, et al. Durability of HBeAg seroconversion following adefovir dipivoxil treatment of chronic hepatitis B (CHB). J Hepatol. 2006;44(Suppl 2):S187
  27. Sherman M. Predicting survival in hepatitis B. Gut. 2005;54:1521–1523
  28. Keeffe EB, Dieterich DT, Han SHB, et al. A treatment algorithm for the management of chronic hepatitis B virus infection in the United States. Clin Gastroenterol Hepatol. 2006;4:936–962
  29. Yuen MF, Yuan HJ, Wong DKH, et al. Prognostic determinants for chronic hepatitis B in Asians: therapeutic implications. Gut. 2005;54:1610–1614

 The study was sponsored by Bristol-Myers Squibb. The sponsor designed the study in collaboration with expert hepatologists. The sponsor also collected the data, monitored study conduct, performed the statistical analyses, and coordinated writing of the manuscript with all authors. The study was conducted in accordance with the ethics principles of the Declaration of Helsinki and in line with Good Clinical Practice guidelines and applicable local regulatory requirements. Written informed consent was obtained from all participants, and financial disclosures were documented and submitted to the U.S. Food and Drug Administration. Statistical analyses were performed in accordance with the Good Clinical Practice guidelines, and the product was subsequently approved by the U.S. Food and Drug Administration. R.G.G. had full access to all the data and accepts full responsibility for the veracity of the data and analysis.

 The authors declare the following conflicts of interest: R.G.G. received a research grant from, and is an advisor to, Bristol-Myers Squibb, A.S.L. received a research grant from Bristol-Myers Squibb, A.S.L., A.G., and K.-H.H. are advisors for Bristol-Myers Squibb, and M.H., J.Y., R.C., H.B.-S. are employees of Bristol-Myers Squibb. T.-T.C., R.A.D., J.S., Y.-C.C., and S.-D.L. have no financial arrangements to disclose.

PII: S0016-5085(07)01482-5

doi: 10.1053/j.gastro.2007.08.025

Gastroenterology
Volume 133, Issue 5 , Pages 1437-1444 , November 2007

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