Gastroenterology
Volume 137, Issue 6 , Pages 2002-2009 , December 2009

Factors That Predict Response of Patients With Hepatitis B e Antigen–Positive Chronic Hepatitis B to Peginterferon-Alfa

  • Erik H.C.J. Buster

      Affiliations

    • Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands
    • ,
  • Bettina E. Hansen

      Affiliations

    • Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands
    • Department of Epidemiology and Biostatistics, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands
    • ,
  • George K.K. Lau

      Affiliations

    • Department of Medicine, Queen Mary Hospital, University of Hong Kong, Hong Kong SAR, China
    • ,
  • Teerha Piratvisuth

      Affiliations

    • Department of Medicine, Songklanakarin Hospital, Songkla, Thailand
    • ,
  • Stefan Zeuzem

      Affiliations

    • Medizinische Klinik I, Klinikum der Johann Wolfgang Goethe-Universität, Frankfurt am Main, Germany
    • ,
  • Ewout W. Steyerberg

      Affiliations

    • Department of Public Health, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands
    • ,
  • Harry L.A. Janssen

      Affiliations

    • Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands
    • Corresponding Author InformationReprint requests Address requests for reprints to: Harry L. A. Janssen, MD, PhD, Department of Gastroenterology and Hepatology, Erasmus MC, University Medical Center Rotterdam's Gravendijkwal 230, Room Ha204, 3015 CE Rotterdam, The Netherlands. fax: 0031-10-4365916

Received 25 March 2009 ,Accepted 26 August 2009.

References 

  1. Lavanchy D. Hepatitis B virus epidemiology, disease burden, treatment, and current and emerging prevention and control measures. J Viral Hepat. 2004;11:97–107
  2. Lok AS, Lai CL, Wu PC, et al. Spontaneous hepatitis B e antigen to antibody seroconversion and reversion in Chinese patients with chronic hepatitis B virus infection. Gastroenterology. 1987;92:1839–1843
  3. Lok AS, McMahon BJ. Chronic hepatitis B. Hepatology. 2007;45:507–539
  4. Liaw YF, Sung JJ, Chow WC, et al. Lamivudine for patients with chronic hepatitis B and advanced liver disease. N Engl J Med. 2004;351:1521–1531
  5. van Zonneveld 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
  6. Buster EH, Flink HJ, Cakaloglu Y, et al. Sustained HBeAg and HBsAg loss after long-term follow-up of HBeAg positive patients treated with peginterferon alpha-2b. Gastroenterology. 2008;135:459–467
  7. Lau DT, Everhart J, Kleiner DE, et al. Long-term follow-up of patients with chronic hepatitis B treated with interferon alfa. Gastroenterology. 1997;113:1660–1667
  8. 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
  9. Chang TT, Gish RG, de Man R, et al. A comparison of entecavir and lamivudine for HBeAg-positive chronic hepatitis B. N Engl J Med. 2006;354:1001–1010
  10. Janssen HL, 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
  11. Lau GK, 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
  12. Marcellin P, Chang TT, 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
  13. Carreno V, Castillo I, Molina J, et al. Long-term follow-up of hepatitis B chronic carriers who responded to interferon therapy. J Hepatol. 1992;15:102–106
  14. Fattovich G, Giustina G, Realdi G, et al. Long-term outcome of hepatitis B e antigen-positive patients with compensated cirrhosis treated with interferon alfa (European Concerted Action on Viral Hepatitis (EUROHEP)). Hepatology. 1997;26:1338–1342
  15. Korenman J, Baker B, Waggoner J, et al. Long-term remission of chronic hepatitis B after alpha-interferon therapy. Ann Intern Med. 1991;114:629–634
  16. Krogsgaard K. The long-term effect of treatment with interferon-alpha 2a in chronic hepatitis B. The Long-Term Follow-up Investigator Group. The European Study Group on Viral Hepatitis (EUROHEP). Executive Team on Anti-Viral Treatment. J Viral Hepat. 1998;5:389–397
  17. Lok AS, Chung HT, Liu VW, et al. Long-term follow-up of chronic hepatitis B patients treated with interferon alfa. Gastroenterology. 1993;105:1833–1838
  18. Niederau C, Heintges T, Lange S, et al. Long-term follow-up of HBeAg-positive patients treated with interferon alfa for chronic hepatitis B. N Engl J Med. 1996;334:1422–1427
  19. van Zonneveld M, Flink HJ, Verhey E, et al. The safety of pegylated interferon alpha-2b in the treatment of chronic hepatitis B: predictive factors for dose reduction and treatment discontinuation. Aliment Pharmacol Ther. 2005;21:1163–1171
  20. van Nunen AB, Hansen BE, Suh DJ, 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;52:420–424
  21. Leung NW, 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
  22. Chang TT, Lai CL, Chien RN, et al. Four years of lamivudine treatment in Chinese patients with chronic hepatitis B. J Gastroenterol Hepatol. 2004;19:1276–1282
  23. Colonno RJ, Rose R, Baldick CJ, et al. Entecavir resistance is rare in nucleoside naive patients with hepatitis B. Hepatology. 2006;44:1656–1665
  24. Hadziyannis SJ, Tassopoulos NC, Heathcote EJ, et al. Long-term therapy with adefovir dipivoxil for HBeAg-negative chronic hepatitis B for up to 5 years. Gastroenterology. 2006;131:1743–1751
  25. Cooksley G, Lau GKK, Liaw YF, et al. Effects of genotype and other baseline factors on response to peginterferon alfa-2a (40 kDa) (Pegasys®) in HBeAg-positive chronic hepatitis B: results from a large, randomised study. J Hepatol. 2005;42:S30
  26. Bonino F, Lau GKK, Marcellin P, et al. The first detailed analysis of predictors of response in HBeAg-negative chronic hepatitis B: data from a multicenter, randomized, partially double-blind study of peginterferon-alfa-2a (4-KD) (Pegasys®) alone or in combination with lamivudine vs lamivudine alone. Hepatology. 2004;40:A1142
  27. European Association for the study of the liver. EASL Clinical Practice Guidelines: management of chronic hepatitis B. J Hepatol. 2009;50:227–242
  28. Pas SD, Fries E, De Man RA, et al. Development of a quantitative real-time detection assay for hepatitis B virus DNA and comparison with two commercial assays. J Clin Microbiol. 2000;38:2897–2901
  29. Harrell FE. Regression modeling strategies: with applications to linear models, logistic regression, and survival analysis. New York, NY: Springer–Verlag; 2001;
  30. Steyerberg EW, Eijkemans MJ, Harrell FE, et al. Prognostic modelling with logistic regression analysis: a comparison of selection and estimation methods in small data sets. Stat Med. 2000;19:1059–1079
  31. Steyerberg EW, Harrell FE, Borsboom GJ, et al. Internal validation of predictive models: efficiency of some procedures for logistic regression analysis. J Clin Epidemiol. 2001;54:774–781
  32. Harrell FE. Regression modeling strategies with applications to linear models, logistic regression, and survival analysis. New York: Springer-Verlag, LLC; 2006;
  33. de Franchis R, Hadengue A, Lau G, et al. EASL International Consensus Conference on Hepatitis B. 13-14 September, 2002, Geneva, Switzerland. Consensus statement (long version) J Hepatol. 2003;39:S3–S25
  34. Liaw YF, Leung N, Kao JH, et al. Asian-Pacific consensus statement on the management of chronic hepatitis B: a 2008 update. Hepatol Int. 2008;2:263–283
  35. Chien RN, Yeh CT, Tsai SL, et al. Determinants for sustained HBeAg response to lamivudine therapy. Hepatology. 2003;38:1267–1273
  36. Ryu SH, Chung YH, Choi MH, et al. Long-term additional lamivudine therapy enhances durability of lamivudine-induced HBeAg loss: a prospective study. J Hepatol. 2003;39:614–619
  37. Lai CL, Gane E, Liaw YF, et al. Telbivudine versus lamivudine in patients with chronic hepatitis B. N Engl J Med. 2007;357:2576–2588
  38. Poynard T, Hou JL, Chutaputti A, et al. Sustained durability of HBeAg seroconversion in chronic hepatitis B patients after treatment with telbivudine. J Hepatol. 2008;48:S263–S264
  39. Zoulim F, Perrillo R. Hepatitis B: reflections on the current approach to antiviral therapy. J Hepatol. 2008;48(Suppl 1):S2–S19
  40. Craxi A, Di Bona D, Camma C. Interferon-alpha for HBeAg-positive chronic hepatitis B. J Hepatol. 2003;39(Suppl 1):S99–S105
  41. Fried MW, Piratvisuth T, Lau GK, et al. HBeAg and hepatitis B virus DNA as outcome predictors during therapy with peginterferon alfa-2a for HBeAg-positive chronic hepatitis B. Hepatology. 2008;47:428–434
  42. Buster EH, Hansen BE, Zeuzem S, et al. Predicting sustained HBeAg loss after treatment with peginterferon alpha-2b: development and validation of a practical model. Hepatology. 2007;46:684A–685A
  43. Grandjacques C, Pradat P, Stuyver L, et al. Rapid detection of genotypes and mutations in the pre-core promoter and the pre-core region of hepatitis B virus genome: correlation with viral persistence and disease severity. J Hepatol. 2000;33:430–439
  44. Lin SM, Yu ML, Lee CM, et al. Interferon therapy in HBeAg positive chronic hepatitis reduces progression to cirrhosis and hepatocellular carcinoma. J Hepatol. 2007;46:45–52
  45. 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
  46. Iloeje UH, Yang HI, Su J, et al. Predicting cirrhosis risk based on the level of circulating hepatitis B viral load. Gastroenterology. 2006;130:678–686
  47. Marcellin P, Piratvisuth T, Brunetto MR, et al. Virological and biochemical response in patients with HBeAg-negative chronic hepatitis B treated with peginterferon alfa-2a (40kD) with or without lamivudine: results of 4-year follow-up. J Hepatol. 2008;48:S46

 Funding The Peginterferon Alfa-2a HBeAg-Positive Chronic Hepatitis B Study was supported by a research grant from Roche (Basel, Switzerland). The HBV99-01 study was organized and sponsored by the Foundation for Liver Research (SLO), Rotterdam, The Netherlands. Financial support and study medication for the HBV99-01 study was provided by Schering-Plough International (Kenilworth, NJ) and GlaxoSmithKline (Greenford, UK).

 Conflicts of interest These authors disclose the following: Erik H.C.J. Buster received speaker's honoraria from Novartis and Roche; George K. Lau consulted for Roche and Novartis; Teerha Piratvisuth consulted for GlaxoSmithKline, Novartis, and Schering-Plough, and received research support from Roche and Bristol-Myers Squibb; Stefan Zeuzem was a consultant for Bristol-Myers Squibb, Gilead, Novartis, Roche, and Schering-Plough, was on the speaker's bureau for Gilead and Novartis, and received research support from Roche; Harry L. A. Janssen received research support from Bristol-Myers Squibb, Gilead, Novartis, Roche, Schering-Plough, and was a consultant for Bristol-Myers Squibb, Novartis, and Roche. The remaining authors disclose no conflicts. Potential investigator conflicts of interest have not been disclosed to study participants.

PII: S0016-5085(09)01551-0

doi: 10.1053/j.gastro.2009.08.061

Gastroenterology
Volume 137, Issue 6 , Pages 2002-2009 , December 2009

Article Tools

* Image Usage & Resolution