Advertisement

PharmacoEconomics

, Volume 29, Issue 12, pp 1063–1073 | Cite as

Cost-Effectiveness Analysis of Prophylactic Lamivudine Use in Preventing Vertical Transmission of Hepatitis B Virus Infection

  • Hui-Fang Hung
  • Hsiu-Hsi ChenEmail author
Original Research Article Economic Evaluation of Lamivudine Use in Pregnancy

Abstract

Background: As neonates born to mothers with positive hepatitis B e antigen may not be completely protected by hepatitis B vaccination, prophylactic lamivudine use in mothers with high viraemia has been proposed. However, the overall effectiveness and the balance between cost and benefit for such a prophylactic strategy have rarely been addressed. Objective: Using a review of recent literature, we aimed to assess the cost effectiveness, from the Taiwanese societal perspective, of administering prophylactic lamivudine to mothers to reduce vertical transmission of hepatitis B virus and its long-term sequelae in neonates.

Methods: A meta-analysis of three randomized controlled trials was conducted to evaluate the efficacy of lamivudine versus placebo. A Markov decision model was constructed in which in both treatment arms infants received active and passive immunoprophylaxis. An economic evaluation was performed to calculate costs, acute infections averted, and QALYs gained. Probabilistic sensitivity analyses were conducted and a cost-effectiveness acceptability curve drawn. All these analyses were from the societal perspective. Costs ($US) were valued in year 2008 prices.

Result: Supplemental lamivudine use gained an additional 0.0024 QALYs and averted 0.23 acute infections per birth compared with the routine activepassive immunization without lamivudine. The cost-effectiveness analysis suggested that the use of additional prophylactic lamivudine dominated the routine strategy. The acceptability curve suggested that the probability of being cost effective under the willingness-to-pay threshold of $US20 000 was 94%.

Conclusion: This analysis suggests that supplemental use of lamivudine in mothers with high hepatitis B viraemia is effective in reducing vertical transmission and may be cost effective, from a Taiwanese societal perspective, compared with the routine active-passive immunization without lamivudine.

Keywords

Lamivudine Vertical Transmission Perinatal Transmission Supplemental Digital Content Lamivudine Group 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgements

Dr Hung and Professor Chen had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. There were no potential conflicts of interest or sources of funding for either author.

Supplementary material

40273_2012_29121063_MOESM1_ESM.pdf (97 kb)
Supplementary material, approximately 99 KB.

References

  1. 1.
    Stevens CE, Beasley RP, Tsui J, et al. Vertical transmission of hepatitis B antigen in Taiwan. N Engl J Med 1975 Apr 10; 292 (15): 771–4PubMedCrossRefGoogle Scholar
  2. 2.
    Stevens CE, Toy PT, Tong MJ, et al. Perinatal hepatitis B virus transmission in the United States: prevention by passive-active immunization. JAMA 1985 Mar 22-29; 253 (12): 1740–5PubMedCrossRefGoogle Scholar
  3. 3.
    Chen HL, Chang MH, Ni YH, et al. Seroepidemiology of hepatitis B virus infection in children: ten years of mass vaccination in Taiwan. JAMA 1996; 276: 906–8PubMedCrossRefGoogle Scholar
  4. 4.
    del Canho R, Grosheide PM, Mazel JA, et al. Ten-year neonatal hepatitis B vaccination program, the Netherlands, 1982-1992: protective efficacy and long-term immunogenicity. Vaccine 1997 Oct; 15 (15): 1624–30PubMedCrossRefGoogle Scholar
  5. 5.
    Liaw YF, Sung JJ, Chow WC, et al. Lamivudine for patients with chronic hepatitis B and advanced liver disease. N Engl J Med 2004 Oct 7; 351 (15): 1521–31PubMedCrossRefGoogle Scholar
  6. 6.
    McGowan JP, Shah SS. Prevention of perinatal HIV transmission during pregnancy. J Antimicrob Chemother 2000 Nov; 46 (5): 657–68PubMedCrossRefGoogle Scholar
  7. 7.
    Li X, Yang Y, Hou H, et al. Interruption of HBV intrauterine transmission: a clinical study. World J Gastroenterol 2003 Jul; 9 (7): 1501–3PubMedGoogle Scholar
  8. 8.
    van Zonneveld M, van Nunen A, Niesters H, et al. Lamivudine treatment during pregnancy to prevent perinatal transmission of hepatitis B virus infection. J Viral Hepat 2003 Jul; 10 (4): 294–7PubMedCrossRefGoogle Scholar
  9. 9.
    Xu WM, Cui YT, Wang L, et al. Lamivudine in late pregnancy to prevent perinatal transmission of hepatitis B virus infection: amulticentre, randomized, double-blind, placebocontrolled study. J Viral Hepat 2009 Feb; 16 (2): 94–103PubMedCrossRefGoogle Scholar
  10. 10.
    Gilks WR, Richardson S, Spiegelhalter DJ, et al. Markov Chain Monte Carlo in practice. New York: Chapman and Hall, 1996Google Scholar
  11. 11.
    Chen HL, Chang MH, Ni YH, et al. Seroepidemiology of hepatitis B virus infection in children: ten years of mass vaccination in Taiwan. JAMA 1996 Sep 18; 276 (11): 906–8PubMedCrossRefGoogle Scholar
  12. 12.
    Lin DB, Wang HM, Lee YL, et al. Immune status in preschool children born after mass hepatitis B vaccination program in Taiwan. Vaccine 1998 Oct; 16 (17): 1683–7PubMedCrossRefGoogle Scholar
  13. 13.
    Beasley RP, Hwang LY, Lee GC, et al. Prevention of perinatally transmitted hepatitis B virus infections with hepatitis B virus infections with hepatitis B immune globulin and hepatitis B vaccine. Lancet 1983 Nov 12; 2 (8359): 1099–102PubMedCrossRefGoogle Scholar
  14. 14.
    Edmunds WJ, Medley GF, Nokes DJ, et al. Epidemiological patterns of hepatitis B virus (HBV) in highly endemic areas. Epidemiol Infect 1996 Oct; 117 (2): 313–25PubMedCrossRefGoogle Scholar
  15. 15.
    Hsu HY, Chang MH, Chen DS, et al. Baseline seroepidemiology of hepatitis B virus infection in children in Taipei, 1984: a study just before mass hepatitis B vaccination program in Taiwan. J Med Virol 1986 Apr; 18 (4): 301–7PubMedCrossRefGoogle Scholar
  16. 16.
    Ip HM, Lelie PN, Wong VC, et al. Prevention of hepatitis B virus carrier state in infants according to maternal serum levels of HBV DNA. Lancet 1989 Feb 25; 1 (8635): 406–10PubMedCrossRefGoogle Scholar
  17. 17.
    Lee SD, Lo KJ, Wu JC, et al. Prevention of maternal-infant hepatitis B virus transmission by immunization: the role of serum hepatitis B virus DNA. Hepatology 1986 May-Jun; 6 (3): 369–73PubMedCrossRefGoogle Scholar
  18. 18.
    McMahon BJ, Alward WL, Hall DB, et al. Acute hepatitis B virus infection: relation of age to the clinical expression of disease and subsequent development of the carrier state. J Infect Dis 1985 Apr; 151 (4): 599–603PubMedCrossRefGoogle Scholar
  19. 19.
    Shah N, Ostrow D, Altman N, et al. Evolution of acute hepatitis B in homosexual men to chronic hepatitis B: prospective study of placebo recipients in a hepatitis B vaccine trial. Arch Intern Med 1985 May; 145 (5): 881–2PubMedCrossRefGoogle Scholar
  20. 20.
    Tassopoulos NC, Papaevangelou GJ, Sjogren MH, et al. Natural history of acute hepatitis B surface antigenpositive hepatitis in Greek adults. Gastroenterology 1987 Jun; 92 (6): 1844–50PubMedGoogle Scholar
  21. 21.
    Dupuy JM, Frommel D, Alagille D. Severe viral hepatitis type B in infancy. Lancet 1975 Jan 25; 1 (7900): 191–4PubMedCrossRefGoogle Scholar
  22. 22.
    Redeker AG. Viral hepatitis: clinical aspects. Am J Med Sci 1975 Jul-Aug; 270 (1): 9–16PubMedCrossRefGoogle Scholar
  23. 23.
    Karvountzis GG, Redeker AG, Peters RL. Long termfollowup studies of patients surviving fulminant viral hepatitis. Gastroenterology 1974 Nov; 67 (5): 870–7PubMedGoogle Scholar
  24. 24.
    Edmunds WJ, Medley GF, Nokes DJ, et al. The influence of age on the development of the hepatitis B carrier state. Proc Biol Sci 1993 Aug 23; 253 (1337): 197–201PubMedCrossRefGoogle Scholar
  25. 25.
    McMahon BJ, Alberts SR, Wainwright RB, et al. Hepatitis B-related sequelae: prospective study in 1400 hepatitis B surface antigen-positive Alaska native carriers. Arch Intern Med 1990 May; 150 (5): 1051–4PubMedCrossRefGoogle Scholar
  26. 26.
    Kocak N, Ozen H, Yuce A, et al. Long-term follow-up of hepatitis B virus carriers with normal transaminases levels. Turk J Pediatr 1998 Jul-Sep; 40 (3): 365–72PubMedGoogle Scholar
  27. 27.
    Nishida S, Tada R, Nishiwaki T, et al. Seven-year follow-up studies on asymptomatic HBsAg carriers. Sangyo Igaku 1982 May; 24 (3): 253–64PubMedCrossRefGoogle Scholar
  28. 28.
    Yu MW, Hsu FC, Sheen IS, et al. Prospective study of hepatocellular carcinoma and liver cirrhosis in asymptomatic chronic hepatitis B virus carriers. AmJ Epidemiol 1997 Jun 1; 145 (11): 1039–47CrossRefGoogle Scholar
  29. 29.
    McMahon BJ, Holck P, Bulkow L, et al. Serologic and clinical outcomes of 1536 Alaska Natives chronically infected with hepatitis B virus. Ann Intern Med 2001 Nov 6; 135 (9): 759–68PubMedGoogle Scholar
  30. 30.
    Alward WL, McMahon BJ, Hall DB, et al. The long-term serological course of asymptomatic hepatitis B virus carriers and the development of primary hepatocellular carcinoma. J Infect Dis 1985 Apr; 151 (4): 604–9PubMedCrossRefGoogle Scholar
  31. 31.
    Sherman M, Peltekian KM, Lee C. Screening for hepatocellular carcinoma in chronic carriers of hepatitis B virus: incidence and prevalence of hepatocellular carcinoma in a North American urban population. Hepatology 1995 Aug; 22 (2): 432–8PubMedGoogle Scholar
  32. 32.
    Liaw YF, Sheen IS, Chen TJ, et al. Incidence, determinants and significance of delayed clearance of serum HBsAg in chronic hepatitis B virus infection: a prospective study. Hepatology 1991 Apr; 13 (4): 627–31PubMedCrossRefGoogle Scholar
  33. 33.
    Crook PD, Jones ME, Hall AJ. Mortality of hepatitis B surface antigen-positive blood donors in England and Wales. Int J Epidemiol 2003 Feb; 32 (1): 118–24PubMedCrossRefGoogle Scholar
  34. 34.
    Liaw YF, Tai DI, Chu CM, et al. The development of cirrhosis in patients with chronic type B hepatitis: a prospective study. Hepatology 1988; 8 (3): 493–6PubMedCrossRefGoogle Scholar
  35. 35.
    Fattovich G, Brollo L, Giustina G, et al. Natural history and prognostic factors for chronic hepatitis type B. Gut 1991 Mar; 32 (3): 294–8PubMedCrossRefGoogle Scholar
  36. 36.
    Ikeda K, Saitoh S, Suzuki Y, et al. Disease progression and hepatocellular carcinogenesis in patients with chronic viral hepatitis: a prospective observation of 2215 patients. J Hepatol 1998 Jun; 28 (6): 930–8PubMedCrossRefGoogle Scholar
  37. 37.
    Chen DS, Sheu JC, Shung JL. A prospective study on the occurrence of hepatocellular carcinoma in patients with cirrhosis, chronic hepatitis and asymptomatic HBsAg carriers [abstract]. Symposium on Epidemiology and Clinical Trials 1985 Jun 10-12: 1036–49Google Scholar
  38. 38.
    De Groote J, Fevery J, Lepoutre L. Long-term follow-up of chronic active hepatitis of moderate severity. Gut 1978 Jun; 19 (6): 510–3PubMedCrossRefGoogle Scholar
  39. 39.
    Lo KJ, Tong MJ, Chien MC, et al. The natural course of hepatitis B surface antigen-positive chronic active hepatitis in Taiwan. J Infect Dis 1982 Aug; 146 (2): 205–10PubMedCrossRefGoogle Scholar
  40. 40.
    Liaw YF, Tai DI, Chu CM, et al. Early detection of hepatocellular carcinoma in patients with chronic type B hepatitis: a prospective study. Gastroenterology 1986 Feb; 90 (2): 263–7PubMedGoogle Scholar
  41. 41.
    Fattovich G, Giustina G, Schalm SW, et al. Occurrence of hepatocellular carcinoma and decompensation in western European patients with cirrhosis type B. The EUROHEP Study Group on Hepatitis B Virus and Cirrhosis. Hepatology 1995 Jan; 21 (1): 77–82Google Scholar
  42. 42.
    D’Amico G, Morabito A, Pagliaro L, et al. Survival and prognostic indicators in compensated and decompensated cirrhosis. Dig Dis Sci 1986 May; 31 (5): 468–75PubMedCrossRefGoogle Scholar
  43. 43.
    Fattovich G. Natural history and prognosis of hepatitis B. Semin Liver Dis 2003 Feb; 23 (1): 47–58PubMedCrossRefGoogle Scholar
  44. 44.
    Marcellin P, Castelnau C, Martinot-Peignoux M, et al. Natural history of hepatitis B. Minerva Gastroenterol Dietol 2005 Mar; 51 (1): 63–75PubMedGoogle Scholar
  45. 45.
    McMahon BJ, Bulkow L, Harpster A, et al. Screening for hepatocellular carcinoma in Alaska natives infected with chronic hepatitis B: a 16-year population-based study. Hepatology 2000 Oct; 32 (4 Pt 1): 842–6PubMedCrossRefGoogle Scholar
  46. 46.
    Hutton DW, Tan D, So SK, et al. Cost-effectiveness of screening and vaccinating Asian and Pacific Islander adults for hepatitis B. Ann Intern Med 2007 Oct 2; 147 (7): 460–9PubMedGoogle Scholar
  47. 47.
    Bloom BS, Hillman AL, Fendrick AM, et al. A reappraisal of hepatitis B virus vaccination strategies using cost-effectiveness analysis. Ann Intern Med 1993; 118 (4): 298–306PubMedGoogle Scholar
  48. 48.
    Fendrick AM, Lee JH, LaBarge C, et al. Clinical and economic impact of a combination Haemophilus influenzae and hepatitis B vaccine: estimating cost-effectiveness using decision analysis. Arch Pediatr Adolesc Med 1999 Feb; 153 (2): 126–36PubMedGoogle Scholar
  49. 49.
    Ginsberg GM, Shouval D. Cost-benefit analysis of a nationwide neonatal inoculation programme against hepatitis B in an area of intermediate endemicity. J Epidemiol Community Health 1992; 46 (6): 587–94PubMedCrossRefGoogle Scholar
  50. 50.
    Da Villa G, Sepe A. Immunization programme against hepatitis B virus infection in Italy: cost-effectiveness. Vaccine 1999 Mar 26; 17 (13-14): 1734–8PubMedCrossRefGoogle Scholar
  51. 51.
    Shepherd J, Jones J, Takeda A, et al. Adefovir dipivoxil and pegylated interferon alfa-2a for the treatment of chronic hepatitis B: a systematic review and economic evaluation. Health Technol Assess 2006; 10: iii-iv, xi-xiv, 1–183Google Scholar
  52. 52.
    Kanwal F, Gralnek IM, Martin P, et al. Treatment alternatives for chronic hepatitis B virus infection: a costeffectiveness analysis. Ann Intern Med 2005; 142: 821–31PubMedGoogle Scholar
  53. 53.
    Jacobs RJ, Saab S, Meyerhoff AS. The cost effectiveness of hepatitis immunization for US college students. J Am Coll Health 2003; 51: 227–36PubMedCrossRefGoogle Scholar
  54. 54.
    Mofenson LM, Munderi P. Safety of antiretroviral prophylaxis of perinatal transmission for HIV-infected pregnant women and their infants. J Acquir Immune Defic Syndr 2002 Jun 1; 30 (2): 200–15PubMedGoogle Scholar
  55. 55.
    Bain VG, Kneteman NM, Ma MM, et al. Efficacy of lamivudine in chronic hepatitis B patients with active viral replication and decompensated cirrhosis undergoing liver transplantation. Transplantation 1996 Nov 27; 62 (10): 1456–62PubMedCrossRefGoogle Scholar
  56. 56.
    Grellier L, Mutimer D, Ahmed M, et al. Lamivudine prophylaxis against reinfection in liver transplantation for hepatitis B cirrhosis [published erratum appears in Lancet 1997 Feb 1; 349 (9048): 364]. Lancet 1996 Nov 2; 348 (9036): 1212–5PubMedCrossRefGoogle Scholar
  57. 57.
    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 Jul 9; 339 (2): 61–8Google Scholar
  58. 58.
    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 Oct 21; 341 (17): 1256–63PubMedCrossRefGoogle Scholar
  59. 59.
    Tuon FF, Guastini CMdF, Boulos MIC. Acute pancreatitis associated with lamivudine therapy for chronic B hepatitis. Braz J Infect Dis 2008 Aug; 12 (4): 263PubMedCrossRefGoogle Scholar
  60. 60.
    Soylu AR, DÖkmeci G, Tezel A, et al. Lamivudine-induced acute pancreatitis in a patient with decompensated Hbvrelated chronic liver disease. J Clin Gastroenterol 2004 Feb; 38 (2): 134PubMedCrossRefGoogle Scholar
  61. 61.
    Bienvenu L, Burel F, Hofman V, et al. A rare etiology of hepatic steatosis associated with lactic acidosis: the toxicity of antiviral nucleoside analogues. Ann Pathol 2001 Apr; 21 (2): 160–3PubMedGoogle Scholar
  62. 62.
    Nelson M, Azwa A, Sokwala A, et al. Fanconi syndrome and lactic acidosis associated with stavudine and lamivudine therapy. AIDS 2008 Jul 11; 22 (11): 1374–6PubMedCrossRefGoogle Scholar
  63. 63.
    Lai CL, Dienstag J, Schiff E, et al. Prevalence and clinical correlates of YMDD variants during lamivudine therapy for patients with chronic hepatitis B. Clin Infect Dis 2003 Mar 15; 36 (6): 687–96PubMedCrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG 2011

Authors and Affiliations

  1. 1.Hsin-Chu General Hospital, Department of HealthExecutiveYuanTaipeiTaiwan
  2. 2.Division of Biostatistics, Institute of Epidemiology, College of Public HealthNational Taiwan University TaipeiTaipeiTaiwan 100

Personalised recommendations