Hepatology International

, 2:284 | Cite as

The economics of treating chronic hepatitis B in Asia

  • Yock Young Dan
  • Myat Oo Aung
  • Seng Gee Lim
Review Article


Chronic hepatitis B constitutes a significant health and economic burden to Asian countries. Six medications are now approved for the treatment of chronic hepatitis B, but there is still significant uncertainty with regards to treatment outcomes, cost impact, and benefits in view of the absence of long-term outcomes data. Cost-effectiveness Markov modeling thus allows us to project and estimate long-term outcomes based on current data and compare the cost–benefit between different treatment options. However, there are limitations to these reported studies. Cost-utility indices such as cost/quality–adjusted life years (cost/QALY) may not be intuitive to clinicians and patients. These studies are also usually based on first-world economies, using a benchmark of US$50,000/QALY, and cannot be extrapolated directly to Asia-Pacific countries. Cost-effectiveness of various treatment strategies using a combination of cost-effectiveness indices may provide a more complete picture. These include cost/HBeAg seroconversion for HBeAg-positive patients (range: US$19,400–30,800) and cost/HBV DNA negative (PCR assay) for HBeAg-negative patients (range: US$14,400–32,000) over 5-year time horizon; cost per cirrhosis prevented (range: US$326,000–686,000) and cost per HCC prevented (range: US$654,000–1,380,000) over 10-year horizon using data from REVEAL study, cost per end point complication prevented in cirrhotics (US$9,630/year), and cost per HCC prevented in cirrhotics (US$ 27,600/year) over a 32-month horizon, using data from Asia Lamivudine Cirrhosis Study. More potent antivirals with low resistance appear to have lower cost/clinical end point averted. Published reports of cost-utility analysis comparing treatment using conventional cost/QALY show that all treatment modalities fall below the first-world benchmark of US$50,000/QALY but vary in modeling assumptions and in quality, making comparisons difficult. Reimbursement policies affect out-of-pocket expenses to the patient, and increases the proportion of patients who can afford therapy, but generally do not affect cost-effectiveness. In conclusion, cost-effectiveness analysis is an important tool for health care administrators, clinicians, and patients to decide on the optimal therapy for chronic hepatitis B, but the methodology permits considerable leeway for interpretation of results, thus a combination of cost-effective indices may be needed to paint a more complete picture.


Hepatitis B treatment Cost-effectiveness analysis 



The authors thank Deepak Amarapurkar, Henry Chan, Ed Gane, Jia Jidong, Jia-Horng Kao, Mobin Khan, Laurentius Lesmana, Rosmawati Mohammed, Teerha Piravisuth, Jose Sollarno, Seung Kew Yoon, Masao Omata, and Joe Sasadeusz for providing information about reimbursement policies in their countries.


This study was commissioned by the APASL Hepatitis B Guideline Committee. No funding was received from any agency for this study. Yock Young, Dan is a full time employee of the National University of Singapore and has no declarations. Myat Oo, Aung is a full time employee of the Agency for Science, Technology and Research, Singapore and has no declarations. Seng Gee, Lim is an employee of the National University of Singapore and Agency for Science, Technology and Research. He has been an advisory board member for Novartis Pharmaceuticals, Idenix Pharmaceuticals, Triangle Pharmaceuticals, Valeant Pharmaceuticals, Bristol Myers Squibb Pharmaceuticals, and Schering Plough Pharmaceuticals. He is on the Speaker's Bureau for GlaxoSmithKline Pharmaceuticals and Novartis Pharmaceuticals. He is a consultant for CombintoRx. He does not own patents or stocks related to any of these companies.


  1. 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.PubMedCrossRefGoogle Scholar
  2. 2.
    Lesmana LALN-Y, Mahachai V, Phiet PH, Suh DJ, Yao GB. Hepatitis B: overview of the burden of disease in the Asia-Pacific region. Liver Int 2006;26:3–10.CrossRefGoogle Scholar
  3. 3.
    Bosch FX, Ribes J, Cleries R, Diaz M. Epidemiology of hepatocellular carcinoma. Clin Liver Dis 2005;9:191–211, v.Google Scholar
  4. 4.
    Yang BM, Paik SW, Hahn OS, Yi DH, Choi MS, Payne S. Economic evaluation of the societal costs of hepatitis B in South Korea. J Gastroenterol Hepatol 2001;16:301–8.Google Scholar
  5. 5.
    Lok AS, McMahon BJ. Chronic hepatitis B. Hepatology (Baltimore, MD) 2007;45:507–39.CrossRefGoogle Scholar
  6. 6.
    Liaw YF, Sung JJ, Chow WC, et al. Lamivudine for patients with chronic hepatitis B and advanced liver disease. N Engl J Med 2004;351:1521–31.PubMedCrossRefGoogle Scholar
  7. 7.
    Holodniy M. HIV-1 load quantitation: a 17-year perspective. J Infect Dis 2006;194 Suppl 1:S38–44.PubMedCrossRefGoogle Scholar
  8. 8.
    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.PubMedCrossRefGoogle Scholar
  9. 9.
    Iloeje UH, Yang HI, Su J, Jen CL, You SL, Chen CJ. Predicting cirrhosis risk based on the level of circulating hepatitis B viral load. Gastroenterology 2006;130:678–86.PubMedCrossRefGoogle Scholar
  10. 10.
    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.PubMedCrossRefGoogle Scholar
  11. 11.
    Lin SM, Sheen IS, Chien RN, Chu CM, Liaw YF. Long-term beneficial effect of interferon therapy in patients with chronic hepatitis B virus infection. Hepatology (Baltimore, MD) 1999;29:971–5.CrossRefGoogle Scholar
  12. 12.
    Sonnenberg FA, Beck JR. Markov models in medical decision making: a practical guide. Med Decis Making 1993;13:322–38.PubMedCrossRefGoogle Scholar
  13. 13.
    Weinstein MC, O’Brien B, Hornberger J, et al. Principles of good practice for decision analytic modeling in health-care evaluation: report of the ISPOR Task Force on Good Research Practices—Modeling Studies. Value Health 2003;6:9–17.PubMedCrossRefGoogle Scholar
  14. 14.
    Lampertico P, Vigano M, Manenti E, Iavarone M, Lunghi G, Colombo M. Adefovir rapidly suppresses hepatitis B in HBeAg-negative patients developing genotypic resistance to lamivudine. Hepatology (Baltimore, MD) 2005;42:1414–9.CrossRefGoogle Scholar
  15. 15.
    Colonno RJ, Rose R, Baldick CJ, et al. Entecavir resistance is rare in nucleoside naive patients with hepatitis B. Hepatology (Baltimore, MD) 2006;44:1656–65.CrossRefGoogle Scholar
  16. 16.
    Dan YY, Lim SG. Cost effectiveness of chronic Hepatitis B (Abstract). Hepatology 2006;44(S1):562A.Google Scholar
  17. 17.
    Crowley S, Tognarini D, Desmond P, Lees M, Saal G. Introduction of lamivudine for the treatment of chronic hepatitis B: expected clinical and economic outcomes based on 4-year clinical trial data. J Gastroenterol Hepatol 2002;17:153–64.PubMedCrossRefGoogle Scholar
  18. 18.
    Wong JB, Koff RS, Tine F, Pauker SG. Cost-effectiveness of interferon-alpha 2b treatment for hepatitis B e antigen-positive chronic hepatitis B. Ann Intern Med 1995;122:664–75.PubMedGoogle Scholar
  19. 19.
    Kanwal F, Gralnek IM, Martin P, Dulai GS, Farid M, Spiegel BM. Treatment alternatives for chronic hepatitis B virus infection: a cost-effectiveness analysis. Ann Intern Med 2005;142:821–31.PubMedGoogle Scholar
  20. 20.
    Veenstra DL, Sullivan SD, Clarke L, et al. Cost effectiveness of entecavir versus lamivudine with adefovir salvage in HBeAg-positive chronic hepatitis B. PharmacoEconomics 2007;25:963–77.PubMedGoogle Scholar
  21. 21.
    Takeda A, Jones J, Shepherd J, Davidson P, Price A. A systematic review and economic evaluation of adefovir dipivoxil and pegylated interferon-alpha-2a for the treatment of chronic hepatitis B. J Viral Hepat 2007;14:75–88.PubMedCrossRefGoogle Scholar
  22. 22.
    Veenstra DL, Sullivan SD, Dusheiko GM, et al. Cost-effectiveness of peginterferon alpha-2a compared with lamivudine treatment in patients with HBe-antigen-positive chronic hepatitis B in the United Kingdom. Eur J Gastroenterol Hepatol 2007;19:631–8.PubMedCrossRefGoogle Scholar
  23. 23.
    Sullivan SD, Veenstra DL, Chen P-J, Chang T-T, Chuang W-L, Tsai C, et al. Cost-effectiveness of peginterferon alfa-2a compared to lamivudine treatment in patients with HBe-antigen positive chronic hepatitis B in Taiwan. J Gastroenterol Hepatol 2007;22:1494–9.Google Scholar
  24. 24.
    Kanwal F, Farid M, Martin P, et al. Treatment alternatives for hepatitis B cirrhosis: a cost-effectiveness analysis. Am J Gastroenterol 2006;101:2076–89.PubMedCrossRefGoogle Scholar
  25. 25.
    Lai CLGE, Hsu CW. Two-year results from the GLOBE trial in patients with hepatitis B: greater clinical and antiviral efficacy for telbivudine (LdT) vs lamivudine (Abstract). Hepatology (Baltimore, MD) 2006;44:222A.Google Scholar
  26. 26.
    Wong J, Stephen P. Cost-effectiveness of telbivudine versus lamivudine for chronic Hepatitis B (Abstract). J Hepatol 2007;46(S1):S199.Google Scholar
  27. 27.
    Owens DK. Interpretation of cost-effectiveness analyses. J Gen Intern Med 1998;13:716–7.PubMedCrossRefGoogle Scholar
  28. 28.
    WHO. Macroeconomics and health: investing in health for economic development. Report of the Commission on Macroeconomics and Health: Executive Summary. World Health Organisation. 2001.Google Scholar
  29. 29.
    Bank W. GNI 2006 Atlas Method: World Development Indicators database. 2007.Google Scholar
  30. 30.
    Hsieh CR, Kuo CW. Cost of chronic hepatitis B virus infection in Taiwan. J Clin Gastroenterol 2004;38:S148–52.PubMedCrossRefGoogle Scholar
  31. 31.
    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;354:1001–10.PubMedCrossRefGoogle Scholar
  32. 32.
    Dienstag JL, Schiff ER, Wright TL, et al. Lamivudine as initial treatment for chronic hepatitis B in the United States. N Engl J Med 1999;341:1256–63.PubMedCrossRefGoogle Scholar
  33. 33.
    Lai CL, Chien RN, Leung NW, et al. A one-year trial of lamivudine for chronic hepatitis B. Asia Hepatitis Lamivudine Study Group. N Engl J Med 1998;339:61–8.PubMedCrossRefGoogle Scholar
  34. 34.
    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;352:2682–95.PubMedCrossRefGoogle Scholar
  35. 35.
    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;348:808–16.PubMedCrossRefGoogle Scholar
  36. 36.
    Hadziyannis SJ, Tassopoulos NC, Heathcote EJ, et al. Adefovir dipivoxil for the treatment of hepatitis B e antigen-negative chronic hepatitis B. N Engl J Med 2003;348:800–7.PubMedCrossRefGoogle Scholar
  37. 37.
    Lai CL, Shouval D, Lok AS, et al. Entecavir versus lamivudine for patients with HBeAg-negative chronic hepatitis B. N Engl J Med 2006;354:1011–20.PubMedCrossRefGoogle Scholar
  38. 38.
    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;351:1206–17.PubMedCrossRefGoogle Scholar
  39. 39.
    Guan R, Lai CL, Liaw YF, et al. Efficacy and safety of 5 years lamivudine treatment of Chinese patients with chronic hepatitis B. J Gastroenterol Hepatol 2001;16 Suppl 1:A60 (Abstract).Google Scholar
  40. 40.
    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;131:1743–51.PubMedCrossRefGoogle Scholar
  41. 41.
    Marcellin PCT, Lim SG, et al. Long-term efficacy and safety of adefovir dipivoxil for the treatment of HBeAg-positive chronic hepatitis B (CHB) patients in Study GS-98-437. 57th Annual Meeting of the American Association for the Study of Liver Disease. Boston, MA. 2006.Google Scholar
  42. 42.
    Chang TC, Kaymakoglu S. Entecavir maintained virologic suppression through 3 years of treatment in antiviral-naive HBeAg(+) patients (ETV 022/901). 57th Annual Meeting of the American Association for the Study of Liver Disease. Boston, MA. 2006.Google Scholar
  43. 43.
    Dusheiko GM, Roberts JA. Treatment of chronic type B and C hepatitis with interferon alfa: an economic appraisal. Hepatology (Baltimore, MD) 1995;22:1863–73.Google Scholar
  44. 44.
    Shepherd J, Jones J, Takeda A, Davidson P, Price A. Adefovir dipivoxil and pegylated interferon alfa-2a for the treatment of chronic hepatitis B: a systematic review and economic evaluation. Health Technol Assess (Winchester, England) 2006;10:iii–iv, xi–xiv, 1–183.Google Scholar

Copyright information

© Asian Pacific Association for the Study of the Liver 2008

Authors and Affiliations

  • Yock Young Dan
    • 1
    • 2
  • Myat Oo Aung
    • 3
  • Seng Gee Lim
    • 1
    • 2
    • 3
  1. 1.Department of Gastroenterology and HepatologyNational University HospitalSingaporeSingapore
  2. 2.Department of Medicine, Yong Loo Lin School of MedicineNational UniversitySingaporeSingapore
  3. 3.Centre for Molecular Medicine, Agency for Science, Technology and ResearchSingaporeSingapore

Personalised recommendations