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A systematic review and economic evaluation of adefovir dipivoxil and pegylated interferon-alpha-2a for the treatment of chronic hepatitis B


  • The analysis presented here was commissioned by the UK NHS R&D Health Technology Assessment Programme on behalf of the National Institute for Health and Clinical Excellence (NICE), and has been used in the NICE technology appraisal process ( The full report covering the clinical and cost-effectiveness of adefovir dipivoxil and pegylated interferon-alpha-2a for chronic hepatitis B will be available from the NHS R&D Health Technology Assessment Programme (

Dr Andrea Takeda, Southampton Health Technology Assessments Centre (SHTAC), Wessex Institute for Health Research and Development, University of Southampton, Mailpoint 728, Boldrewood, Southampton SO16 7PX, UK.


Summary.  Standard treatments for chronic hepatitis B (CHB) include interferon-alpha (IFN-α) and lamivudine (LAM), but these are associated with adverse effects and viral resistance, respectively. The aim of this systematic review and economic evaluation was to assess the clinical effectiveness and cost-effectiveness of two alternative drugs for the treatment of adults with CHB: adefovir dipivoxil (ADV) and pegylated IFN-α-2a. We searched electronic databases, including Cochrane Systematic Reviews and Medline, for literature that met criteria defined in a research protocol. Retrieved articles were independently assessed for inclusion by two reviewers. We developed a Markov state transition model to estimate the cost-effectiveness (cost-utility) of pegylated IFN-α-2a and of ADV compared with nonpegylated IFN-α-2a, LAM and best supportive care. Seven randomized controlled trials and two systematic reviews met the inclusion criteria for our review of clinical effectiveness. ADV was significantly more effective than placebo or ongoing LAM in reducing levels of hepatitis B virus (HBV) DNA. Rates of hepatitis B e antigen (HBeAg) seroconversion were higher among patients receiving ADV than either placebo or ongoing LAM. Patients treated with pegylated IFN-α-2a, either as monotherapy or in combination with LAM, showed significantly reduced HBV DNA levels compared with patients treated with LAM monotherapy. HBeAg seroconversion rates at follow-up were significantly higher for pegylated IFN-α-2a patients than for those receiving LAM monotherapy. Results of our cost-effectiveness analysis demonstrate that incremental costs per quality adjusted life year (QALY) for a range of comparisons were between £5994 and £16 569, and within the range considered by NHS decision-makers to represent good value for money.