Treatment alternatives for chronic hepatitis B virus infection: a cost-effectiveness analysis

Ann Intern Med. 2005 May 17;142(10):821-31. doi: 10.7326/0003-4819-142-10-200505170-00007.


Background: Treatment options for chronic hepatitis B virus (HBV) infection have disparate risks and benefits. Interferon has clinically significant side effects, and lamivudine is associated with viral resistance. In contrast, adefovir is safe and has lower viral resistance but is more expensive. The most cost-effective approach is uncertain.

Objective: To determine whether and under what circumstances the improved efficacy of adefovir offsets its increased cost compared with lamivudine or interferon.

Design: Cost-utility analysis stratified by hepatitis B e antigen (HBeAg) status.

Data sources: Systematic review of MEDLINE from 1970 to 2005.

Target population: Patients with chronic HBV infection, elevated aminotransferase levels, and no cirrhosis.

Time horizon: Lifetime.

Perspective: Third-party payer.

Interventions: 1) No HBV treatment ("do nothing" strategy), 2) interferon monotherapy, 3) lamivudine monotherapy, 4) adefovir monotherapy, or 5) lamivudine with crossover to adefovir upon resistance ("adefovir salvage" strategy).

Outcome measure: Incremental cost per quality-adjusted life-year (QALY) gained.

Results of base-case analysis: The "do nothing" strategy was least effective yet least expensive. Compared with the "do nothing" strategy, using interferon cost an incremental 6337 dollars to gain 1 additional QALY. Compared with interferon, the adefovir salvage strategy cost an incremental 8446 dollars per QALY gained. Both the lamivudine and adefovir monotherapy strategies were more expensive yet less effective than the alternative strategies and were therefore dominated.

Results of sensitivity analysis: In sensitivity analysis, interferon was most cost-effective in health care systems with tight budgetary constraints and a high prevalence of HBeAg-negative patients.

Limitations: These results apply only to patients with chronic HBV infection, elevated aminotransferase levels, and no clinical or histologic evidence of cirrhosis. They do not apply to alternative populations.

Conclusions: Neither lamivudine nor adefovir monotherapy is cost-effective in chronic HBV infection. However, a hybrid salvage strategy reserving adefovir only for lamivudine-associated viral resistance may be highly cost-effective across most health care settings. Interferon therapy may still be preferred in health care systems with limited resources, especially in those serving populations with a high prevalence of HBeAg-negative HBV.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenine / analogs & derivatives*
  • Adenine / economics
  • Adenine / therapeutic use
  • Antiviral Agents / economics*
  • Antiviral Agents / therapeutic use*
  • Cost-Benefit Analysis
  • Decision Support Techniques
  • Hepatitis B e Antigens / blood
  • Hepatitis B virus / immunology
  • Hepatitis B, Chronic / drug therapy*
  • Hepatitis B, Chronic / enzymology
  • Hepatitis B, Chronic / virology
  • Humans
  • Interferon alpha-2
  • Interferon-alpha / economics
  • Interferon-alpha / therapeutic use
  • Lamivudine / economics
  • Lamivudine / therapeutic use
  • Liver / enzymology
  • Markov Chains
  • Organophosphonates / economics
  • Organophosphonates / therapeutic use
  • Recombinant Proteins
  • Salvage Therapy
  • Sensitivity and Specificity
  • Transaminases / blood


  • Antiviral Agents
  • Hepatitis B e Antigens
  • Interferon alpha-2
  • Interferon-alpha
  • Organophosphonates
  • Recombinant Proteins
  • Lamivudine
  • adefovir
  • Transaminases
  • Adenine