Advertisement

Disease Management and Health Outcomes

, Volume 9, Issue 4, pp 215–234 | Cite as

Management of Chronic Hepatitis B

Defining the Role of Lamivudine
Drugs in Disease Management

Abstract

According to the WHO, approximately 350 million people have chronic hepatitis B. Individuals with chronic hepatitis B have a highly variable and unpredictable clinical course and are at risk for developing cirrhosis and hepatocellular carcinoma. Lamivudine is the only oral antiviral agent approved for the treatment of patients with chronic hepatitis B.

Lamivudine is useful in a wide range of patients with chronic hepatitis B and ongoing viral replication. In patients with compensated liver disease treated for 52 weeks in multicenter randomized, double-blind clinical studies, lamivudine 100 mg/day inhibited hepatitis B virus (HBV) replication, normalized ALT levels, produced significant reductions in hepatic necroinflammatory activity and halted the progression of fibrosis compared with placebo. Hepatitis B e antigen (HBeAg) seroconversion rates were also increased during treatment with the drug compared with placebo.

In patients who continued to receive the drug after the completion of these trials, improvements in liver histology were maintained and HBeAg seroconversion rates increased in proportion to the duration of treatment.

Pretreatment ALT levels were predictive of HBeAgseroconversion. In patients with baseline ALT levels ≥2-fold higher than the upper limit of normal, seroconversion rates were significantly higher than in those with lower baseline values.

Data from 2 randomized studies indicate that sequential therapy with lamivudine for 8 weeks and then lamivudine plus interferon-α for 16 weeks provides no greater benefit than that of monotherapy with lamivudine for 52 weeks or interferon-α for 16 weeks.

According to data from noncomparative studies, lamivudine 100 or 150 mg/day resulted in clinical stabilization, significant reductions in Child-Pugh-Turcotte scores and loss of HBeAg in many patients with decompensated liver disease. Moreover, some patients have been placed on inactive status for liver transplantation after treatment with the drug.

Lamivudine-resistant HBV variants have been isolated from patients with chronic hepatitis B during treatment with lamivudine. The prevalence of these variants increases with the duration of treatment; however, their long term clinical significance has not been established.

Lamivudine is well tolerated. The frequency of adverse events in lamivudine or placebo recipients was similar in a pooled analysis of clinical trial data. Nonetheless, patients must be monitored for the emergence of lamivudine-resistant variants and elevated liver enzyme levels (ALT flares).

In a series of economic models, use of lamivudine was predicted to reduce the cost per case of cirrhosis prevented and increase mean life expectancy compared with use of interferon-α in the US. Other analyses, which incorporated a fixed drug budget scenario, concluded that use of lamivudine would increase the number of successfully treated patients by 2- to 3-fold compared with interferon-α, because of lower acquisition costs.

In conclusion, lamivudine is useful in a wide range of patients with chronic hepatitis B and ongoing viral replication.

Keywords

Chronic Hepatitis Lamivudine HBeAg Seroconversion Decompensated Liver Disease HBeAg Seroconversion Rate 
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.

References

  1. 1.
    Perry CM, Faulds D. Lamivudine: a review of its antiviral activity, pharmacokinetic properties and therapeutic efficacy in the management of HIV infection. Drugs 1997 Apr; 53: 657–80PubMedCrossRefGoogle Scholar
  2. 2.
    Perry CM, Barman Balfour JA. Management of HIV infection: the potential role of the lamivudine/zidovudine combination formulation. Dis Manage Health Outcomes 1998 Nov; 4(5): 277–93CrossRefGoogle Scholar
  3. 3.
    Jarvis B, Faulds D. Lamivudine: a review of its therapeutic potential in chronic hepatitis B. Drugs 1999 Jul; 58: 101–41PubMedCrossRefGoogle Scholar
  4. 4.
    Leung N. Nucleoside analogues in the treatment of chronic hepatitis B. J Gastroenterol Hepatol 2000 May; 15 Suppl.: E53–60PubMedCrossRefGoogle Scholar
  5. 5.
    Benhamou Y, Katlama C, Lunel F, et al. Effects of lamivudine on replication of hepatitis B virus in HIV-infected men. Ann Intern Med 1996 Nov 1; 125: 705–12PubMedGoogle Scholar
  6. 6.
    Dore GJ, Cooper DA, Barrett C, et al. Dual efficacy of lamivudine treatment in human immunodeficiency virus/hepatitis B virus-coinfected persons in a randomized, controlled study (CAESAR). The CAESAR Coordinating Committee. J Infect Dis 1999 Sep; 180: 607–13PubMedCrossRefGoogle Scholar
  7. 7.
    Grellier L, Mutimer D, Ahmed M, et al. Lamivudine prophylaxis against reinfection in liver transplantation for hepatitis B cirrhosis. Lancet 1996 Nov 2; 348: 1212–5PubMedCrossRefGoogle Scholar
  8. 8.
    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: 1456–62PubMedCrossRefGoogle Scholar
  9. 9.
    Perrillo R, Rakela J, Dienstag J, et al. Multicenter study of lamivudine therapy for hepatitis B after liver transplantation. Hepatology 1999; 29: 1581–6PubMedCrossRefGoogle Scholar
  10. 10.
    Gugenheim J, Baldini E, Ouzan D, et al. Good results of lamivudine in hepatitis B surface antigen-positive patients with active viral replication before liver transplantation. Transplant Proc 1999 Feb–Mar; 31: 554–5PubMedCrossRefGoogle Scholar
  11. 11.
    Lo CM, Fan ST, Lai CL, et al. Lamivudine prophylaxis in liver transplantation for hepatitis B in Asians. Transplant Proc 1999 Feb–Mar; 31: 535–6PubMedCrossRefGoogle Scholar
  12. 12.
    Nery JR, Weppler D, Rodriguez M, et al. Efficacy of lamivudine in controlling hepatitis B virus recurrence after liver transplantation. Transplantation 1998 Jun 27; 65: 1615–21PubMedCrossRefGoogle Scholar
  13. 13.
    Yao FY, Osorio RW, Roberts JP, et al. Intramuscular hepatitis B immune globulin combined with lamivudine for prophylaxis against hepatitis B recurrence after liver transplantation. Liver Transpl Surg 1999 Nov; 5: 491–6PubMedCrossRefGoogle Scholar
  14. 14.
    Yoshida EM, Erb SR, Partovi N, et al. Liver transplantation for chronic hepatitis B infection with the use of combination lamivudine and low-dose hepatitis B immune globulin. Liver Transpl 1999 Nov; 5: 520–5CrossRefGoogle Scholar
  15. 15.
    McCaughan GW, Spencer J, Koorey D, et al. Lamivudine therapy in patients undergoing liver transplantation for hepatitis B virus precore mutant-associated infection: high resistance rates in treatment of recurrence but universal prevention if used as prophylaxis with very low dose hepatitis B immune globulin. Liver Transpl Surg 1999 Nov; 5: 512–9PubMedCrossRefGoogle Scholar
  16. 16.
    Han S-HB, Ofman J, Holt C, et al. An efficacy and costeffectiveness analysis of combination hepatitis B immune globulin and lamivudine to prevent recurrent hepatitis B after orthotopic liver transplantation compared with hepatitis B immune globulin monotherapy. Liver Transpl 2000 Nov; 6(6): 741–8PubMedCrossRefGoogle Scholar
  17. 17.
    Shouval D, Samuel D. Hepatitis B immune globulin to prevent hepatitis B virus graft reinfection following liver transplantation: a concise review. Hepatology 2000 Dec; 32(6): 1189–95PubMedCrossRefGoogle Scholar
  18. 18.
    Lee WM. Hepatitis B virus infection. N Engl J Med 1997 Dec 11; 337: 1733–45PubMedCrossRefGoogle Scholar
  19. 19.
    Alter MJ, Mast EE. The epidemiology of viral hepatitis in the United States. Gastroenterol Clin North Am 1994 Sep; 23(3): 437–55PubMedGoogle Scholar
  20. 20.
    Chu C-M. Natural history of chronic hepatitis B virus infection in adults with emphasis on the occurrence of cirrhosis and hepatocellular carcinoma. J Gastroenterol Hepatol 2000 May; 15 Suppl.: E25–30PubMedCrossRefGoogle Scholar
  21. 21.
    Lok ASF, Lai C-L, Wu P-C, et al. Spontaneous hepatitis B e antigen to antibody seroconversion and reversion in Chinese patients with chronic hepatitis B virus infection. Gastroenterology 1987; 92: 1839–43PubMedGoogle Scholar
  22. 22.
    Imperial JC. Natural history of chronic hepatitis B and C. J Gastroenterol Hepatol 1999 May; 14 Suppl.: 1–5CrossRefGoogle Scholar
  23. 23.
    Anderson MG, Murray-Lyon IM. Natural history of the HBsAg carrier. Gut 1985 Aug; 26: 848–60PubMedCrossRefGoogle Scholar
  24. 24.
    Yuen M-F, Lai C-L. Natural history of chronic hepatitis B virus infection. J Gastroenterol Hepatol 2000 May; 15 Suppl.: E20–24PubMedCrossRefGoogle Scholar
  25. 25.
    Fattovich G, Giustina G, Sanchez-Tapias J, et al. Delayed clearance of serum HBsAg in compensated cirrhosis B: relation to interferon alpha therapy and disease prognosis. Am J Gastroenterol 1998; 93(6): 896–900PubMedCrossRefGoogle Scholar
  26. 26.
    Di Marco V, Lo Iacono O, Cammà C, et al. The long-term course of chronic hepatitis B. Hepatology 1999 Jul; 30: 257–64PubMedCrossRefGoogle Scholar
  27. 27.
    Chun YK, Kim JY, Woo HJ, et al. No significant correlation exists between core promoter mutations, viral replication, and liver damage in chronic hepatitis B infection. Hepatology 2000 Nov; 32(5): 1154–62PubMedCrossRefGoogle Scholar
  28. 28.
    Fattovich G, Brollo L, Giustina G, et al. Natural history and prognostic factors for chronic hepatitis type B. Gut 1991; 32: 294–8PubMedCrossRefGoogle Scholar
  29. 29.
    Liaw YF, Tai DI, Chu CM, et al. The development of cirrhosis in patients with chronic type B hepatitis: a prospective study. Hepatology 1988 May–Jun; 8(3): 493–6PubMedCrossRefGoogle Scholar
  30. 30.
    de Jongh FE, Janssen HLA, De Man RA, et al. Survival and prognostic indicators in hepatitis B surface antigen-positive cirrhosis of the liver. Gastroenterology 1992; 103: 1630–5PubMedGoogle Scholar
  31. 31.
    Kao J-H, Chen P-J, Lai M-Y, et al. Hepatitis B genotypes correlate with clinical outcomes in patients with chronic hepatitis B. Gastroenterology 2000 Mar; 118(3): 554–9PubMedCrossRefGoogle Scholar
  32. 32.
    Beasley RP. Hepatitis B virus the major etiology of hepatocellular carcinoma. Cancer 1988 May 15; 61(10): 1942–56PubMedCrossRefGoogle Scholar
  33. 33.
    Idilman R, De Maria N, Colantoni A, et al. Pathogenesis of hepatitis B and C-induced hepatocellular carcinoma. J Viral Hepatitis 1998; 5: 285–99CrossRefGoogle Scholar
  34. 34.
    El-Serag HB, Mason AC. Rising incidence of hepatocellular carcinoma in the United States. N Engl J Med 1999; 340: 745–50PubMedCrossRefGoogle Scholar
  35. 35.
    Zuckerman AJ. Prevention of primary liver cancer by immunization. N Engl J Med 1997; 336: 1906–7PubMedCrossRefGoogle Scholar
  36. 36.
    Hsieh C-C, Tzonou A, Zavitsanos X, et al. Age at first establishment of chronic hepatitis B virus infection and hepato-cellular carcinoma risk: a birth order study. Am J Epidemiol 1992; 136(9): 1115–21PubMedGoogle Scholar
  37. 37.
    Ince N, Wands JR. The increasing incidence of hepatocellular carcinoma. N Engl J Med 1999; 340: 798–9PubMedCrossRefGoogle Scholar
  38. 38.
    Lee CM, Lu SN, Changchien CS, et al. Age, gender, and local geographic variations of viral etiology of hepatocellular carcinoma in a hyperendemic area for hepatitis B virus infection. Cancer 1999 Oct 1; 86: 1143–50PubMedCrossRefGoogle Scholar
  39. 39.
    El-Serag HB, Mason AC, Key C. Trends in survival of patients with hepatocellular carcinoma between 1977 and 1996 in the United States. Hepatology 2001 Jan; 33(1): 62–5PubMedCrossRefGoogle Scholar
  40. 40.
    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; 32: 842–6PubMedCrossRefGoogle Scholar
  41. 41.
    Zuckerman AJ. More than third of world’s population has been infected with hepatitis B virus [letter; comment]. BMJ 1999 May 1; 318: 1213PubMedCrossRefGoogle Scholar
  42. 42.
    Van Damme P, Vellinga A. Epidemiology of hepatitis B and C in Europe. Acta Gastroenterol Belg 1998 Apr–Jun; 61: 175–82PubMedGoogle Scholar
  43. 43.
    Van Damme P, Kane M, Meheus A. Integration of hepatitis B vaccination into national immunisation programmes. Viral Hepatitis Prevention Board [see comments]. BMJ 1997 Apr 5; 314: 1033–6PubMedCrossRefGoogle Scholar
  44. 44.
    Torres JR. Hepatitis B and hepatitis delta virus infection in South America. Gut 1996; 38 Suppl. 2: S48–55PubMedCrossRefGoogle Scholar
  45. 45.
    Lansang MA. Epidemiology and control of hepatitis B infection: a perspective from the Philippines, Asia. Gut 1996; 38 Suppl. 2: S43–7PubMedCrossRefGoogle Scholar
  46. 46.
    Yao GB. Importance of perinatal versus horizontal transmission of hepatitis B virus infection in China. Gut 1996; 38 Suppl. 2: S39–42PubMedCrossRefGoogle Scholar
  47. 47.
    Kew MC. Progress towards the comprehensive control of hepatitis B in Africa: a view from South Africa. Gut 1996; 38 Suppl. 2: S31–6PubMedCrossRefGoogle Scholar
  48. 48.
    Toukan AU. Hepatitis B in the Middle East: aspects of epidemiology and liver disease after infection. Gut 1996; 38 Suppl. 2: S2–4PubMedCrossRefGoogle Scholar
  49. 49.
    Gust ID. Epidemiology of hepatitis B infection in the Western Pacific and South East Asia. Gut 1996; 38 Suppl. 2: S18–23PubMedCrossRefGoogle Scholar
  50. 50.
    Guan R. Hepatitis B virus infection in Singapore. Gut 1996; 38 Suppl. 2: S13–7PubMedCrossRefGoogle Scholar
  51. 51.
    Kiire CF. The epidemiology and prophylaxis of hepatitis B in sub-Saharan Africa: a view from tropical and subtropical Africa. Gut 1996; 38 Suppl. 2: S5–12PubMedCrossRefGoogle Scholar
  52. 52.
    Blakely T, Salmond C, Tobias M. Hepatitis B virus carrier prevalence in New Zealand: population estimates using the 1987 police and customs personnel survey. N Z Med J 1998 Apr 24; 111: 142–4PubMedGoogle Scholar
  53. 53.
    Prakash C, Sharma RS, Bhatia R, et al. Prevalence in North India of hepatitis B carrier state amongst pregnant women. Southeast Asian J Trop Med Public Health 1998 Mar; 29: 80–4PubMedGoogle Scholar
  54. 54.
    Pebody RG, Ruutu P, Nohynek H, et al. Changing epidemiology of hepatitis B infection in Finland. Scand J Infect Dis 1999; 31(3): 251–4PubMedCrossRefGoogle Scholar
  55. 55.
    Dutra Souto FJ, Fernandes Fontes CJ, Coimbra Gaspar AM, et al. Hepatitis B virus infection in immigrants to the southern Brazilian Amazon. Trans R Soc Trop Med Hyg 1998 May–Jun; 92: 282–4CrossRefGoogle Scholar
  56. 56.
    Roure C. Overview of epidemiology and disease burden of hepatitis B in the European region. Vaccine 1995; 13 Suppl. 1: S18–21PubMedGoogle Scholar
  57. 57.
    McQuillan GM, Coleman PJ, Kruszon-Moran D, et al. Prevalence of hepatitis B virus infection in the United States: the National Health and Nutrition Examination Surveys, 1976 through 1994. Am J Public Health 1999 Jan; 89(1): 14–8PubMedCrossRefGoogle Scholar
  58. 58.
    Coleman PJ, McQuillan GM, Moyer LA, et al. Incidence of hepatitis B virus infection in the United States, 1976–1994: estimates from the National Health and Nutrition Examination Surveys. J Infect Dis 1998 Oct; 178: 954–9PubMedCrossRefGoogle Scholar
  59. 59.
    Wong JB. Interferon treatment for chronic hepatitis B or C infection: costs and effectiveness. Acta Gastroenterol Belg 1998 Apr–Jun; 61: 238–42PubMedGoogle Scholar
  60. 60.
    Wong JB, Koff RS, Tinè F, et al. Cost-effectiveness of interferon-α2b treatment for hepatitis B e antigen-positive chronic hepatitis B. Ann Intern Med 1995; 122: 664–75PubMedGoogle Scholar
  61. 61.
    Metcalf M, Brown N, Peterson S, et al. Health care costs associated with chronic hepatitis B. Am J Health System Pharm 1999 Feb 1; 56: 232–6Google Scholar
  62. 62.
    Yang B-M, Paik S-W, Hahn O-S, et al. Direct and indirect cost of hepatitis B in Korea [abstract no. 759]. Hepatology 1999 Oct; 30 (4 Pt 2): 350AGoogle Scholar
  63. 63.
    Haiderali AM, Villa K, Schrammel P. Cost-effectiveness of lamivudine for the treatment of chronic hepatitis B in Canada [abstract]. Hepatology 1999 Oct; 30 (4 Pt 2): 347AGoogle Scholar
  64. 64.
    Miller DW, Chatterton ML. An economic evaluation of lamivudine for the treatment of chronic hepatitis B infection in China [abstract no. 2437]. Hepatology 1998 Oct; 28 (4 Pt 2) Suppl.: 772AGoogle Scholar
  65. 65.
    Lau GKK, Cheung R, Payne SL, et al. Cost-effectiveness of one-year treatment with lamivudine (Zeffix) or a single course of A-interferon in chronic hepatitis B [abstract no. 1720]. Hepatology 2000 Oct; 32 (4 Pt 2): 589ACrossRefGoogle Scholar
  66. 66.
    From the Centers for Disease Control and Prevention. Update: recommendations to prevent hepatitis B virus transmission—United States. JAMA 1999 Mar 3; 281: 790CrossRefGoogle Scholar
  67. 67.
    Mahoney FJ. Update on diagnosis, management, and prevention of hepatitis B virus infection. Clin Microbiol Rev 1999 Apr; 12: 351PubMedGoogle Scholar
  68. 68.
    Core Working Party for Asia-Pacific Consensus on Hepatitis B and C. Consensus statements on the prevention and management of hepatitis B and hepatitis C in the Asia-Pacific region. J Gastroenterol Hepatol 2000 Aug; 15(8): 825–41CrossRefGoogle Scholar
  69. 69.
    Lemon SM, Thomas DL. Vaccines to prevent viral hepatitis. N Engl J Med 1997 Jan 16; 336: 196–203PubMedCrossRefGoogle Scholar
  70. 70.
    Vryheid RE, Kane MA, Muller N, et al. Infant and adolescent hepatitis B immunization up to 1999: a global overview. Vaccine 2001; 19: 1026–37CrossRefGoogle Scholar
  71. 71.
    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
  72. 72.
    Chang M-H, Chen C-J, Lai M-S, et al. Universal hepatitis B vaccination in Taiwan and the incidence of hepatocellular carcinoma in children. N Engl J Med 1997 Jun 26; 336(26): 1855–9PubMedCrossRefGoogle Scholar
  73. 73.
    Chang M-H, Shau W-Y, Chen C-J, et al. Hepatitis B vaccination and hepatocellular carcinoma rates in boys and girls. JAMA 2000 Dec 20; 284(23): 3040–2PubMedCrossRefGoogle Scholar
  74. 74.
    Hoofnagle JH, Di Bisceglie AM. The treatment of chronic viral hepatitis. N Engl J Med 1997 Jan 30; 336: 347–56PubMedCrossRefGoogle Scholar
  75. 75.
    Glaxo Wellcome Inc. Epivir-HBV (lamivudine) product information. Glaxo Wellcome Inc. Research Triangle Park, NC, USA, Apr 2000Google Scholar
  76. 76.
    Zdilar D, Franco-Bronson K, Buchler N, et al. Hepatitis C, interferon alfa, and depression. Hepatology 2000 Jun; 31(6): 1207–11PubMedCrossRefGoogle Scholar
  77. 77.
    Guan R. Interferon monotherapy in chronic hepatitis B. J Gastroenterol Hepatol 2000 May; 15 Suppl.: E34–40PubMedCrossRefGoogle Scholar
  78. 78.
    Fattovich G, Giustina G, Favarato S, et al. A survey of adverse events in 11 241 patients with chronic viral hepatitis treated with alfa interferon. J Hepatol 1996; 24: 38–47PubMedCrossRefGoogle Scholar
  79. 79.
    Sokal EM, Roberts EA, Mieli-Vergani G, et al. A dose ranging study of the pharmacokinetics, safety, and preliminary efficacy of lamivudine in children and adolescents with chronic hepatitis B. Antimicrob Agents Chemother 2000 Mar; 44: 590–7PubMedCrossRefGoogle Scholar
  80. 80.
    Lok ASF, Ghany MG, Watson G, et al. Predictive value of aminotransferase and hepatitis B virus DNA levels on response to interferon therapy for chronic hepatitis B. J Viral Hepatitis 1998; 5: 171–8CrossRefGoogle Scholar
  81. 81.
    Malik AH, Lee WM. Hepatitis B therapy: the plot thickens [editorial]. Hepatology 1999 Aug; 30(2): 579–81PubMedCrossRefGoogle Scholar
  82. 82.
    Perrillo RP, Schiff ER, Davis GL, et al. A randomized, controlled trial of interferon alfa-2b alone and after prednisone withdrawal for the treatment of chronic hepatitis B. N Engl J Med 1990 Aug 2; 323(5): 295–301PubMedCrossRefGoogle Scholar
  83. 83.
    Krogsgaard K, Bindslev N, Christensen E, et al. The treatment effect of alpha interferon in chronic hepatitis B is independent of pre-treatment variables. Results based on individual patient data from 10 clinical controlled trials. J Hepatol 1994; 21: 646–55PubMedCrossRefGoogle Scholar
  84. 84.
    Erhardt A, Reineke U, Blondin D, et al. Mutations of the core promoter and response to interferon treatment in chronic replicative hepatitis B. Hepatology 2000; 31: 716–25PubMedCrossRefGoogle Scholar
  85. 85.
    Wong DKH, Cheung AM, O’Rourke K, et al. Effect of alphainterferon treatment in patients with hepatitis B e antigenpositive chronic hepatitis B: a meta-analysis. Ann Intern Med 1993; 119: 312–23PubMedGoogle Scholar
  86. 86.
    Korenman J, Baker B, Waggoner J, et al. Long-term remission of chronic hepatitis B after alpha-interferon therapy. Ann Intern Med 1991 Apr 15; 114(8): 629–34PubMedGoogle Scholar
  87. 87.
    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: 1422–7PubMedCrossRefGoogle Scholar
  88. 88.
    Lau DT, Everhart J, Kleiner DE, et al. Long-term follow-up of patients with chronic hepatitis B treated with interferon alfa. Gastroenterology 1997 Nov; 113(5): 1660–7PubMedCrossRefGoogle Scholar
  89. 89.
    Brook MG, Petrovic L, McDonald JA, et al. Histological improvement after anti-viral treatment for chronic hepatitis B virus infection. J Hepatol 1989; 8: 218–25PubMedCrossRefGoogle Scholar
  90. 90.
    Hoofnagle JH, Di Bisceglie A, Waggoner JG, et al. Interferon alfa for patients with clinically apparent cirrhosis due to chronic hepatitis B. Gastroenterology 1993 Apr; 104(4): 1116–21PubMedGoogle Scholar
  91. 91.
    Alberti A, Fattovich G. Interferon therapy for the anti-HBe positive form of chronic hepatitis B. Antiviral Res 1994 Jul; 24(2–3): 145–53PubMedCrossRefGoogle Scholar
  92. 92.
    Brunetto MR, Giarin M, Saracco G, et al. Hepatitis B virus unable to secrete e antigen and response to interferon in chronic hepatitis B. Gastroenterology 1993; 105: 845–50PubMedGoogle Scholar
  93. 93.
    Hunt CM, McGill JM, Allen MI, et al. Clinical relevance of hepatitis B viral mutations. Hepatology 2000 May; 31(5): 1037–44PubMedCrossRefGoogle Scholar
  94. 94.
    Rossana M, Oliveri F, Rocca G, et al. Natural course and response to interferon of chronic hepatitis B accompanied by antibody to hepatitis B e antigen. Hepatology 1989; 10(2): 198–202CrossRefGoogle Scholar
  95. 95.
    Guptan RKC, Thakur V, Malhotra V, et al. Low-dose recombinant interferon therapy in anti-HBe-positive chronic hepatitis B in Asian Indians. J Gastroenterol Hepatol 1998; 13: 675–9PubMedCrossRefGoogle Scholar
  96. 96.
    Lai C-L, Chien R-N, Leung NWY, et al. A one-year trial of lamivudine for chronic hepatitis B. N Engl J Med 1998; 339(2): 61–8PubMedCrossRefGoogle Scholar
  97. 97.
    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: 1256–63PubMedCrossRefGoogle Scholar
  98. 98.
    Tassopoulos NC, Volpes R, Pastore G, et al. Efficacy of lamivudine in patients with hepatitis B e antigen-negative/hepatitis B virus DNA-positive (precore mutant) chronic hepatitis B. Hepatology 1999; 29: 889–96PubMedCrossRefGoogle Scholar
  99. 99.
    British National Formulary. Lamivudine. No. 40. London: The Pharmaceutical Press, 2000 Sep: 293Google Scholar
  100. 100.
    Johnson MA, Moore KHP, Yuen GJ, et al. Clinical pharmacokinetics of lamivudine. Clin Pharmacokinet 1999; 36: 41–66PubMedCrossRefGoogle Scholar
  101. 101.
    Dienstag JL, Lai CL, Hann HWL, et al. Natural history and lamivudine response in Asians versus Westerners with chronic hepatitis B [abstract]. 39th Interscience Conference on Antimicrobial Agents and Chemotherapy; 1999 Sep 26–29; San Francisco, 446Google Scholar
  102. 102.
    Schiff E, Karayalcin S, Grimm I, et al. A placebo controlled study of lamivudine and interferon alpha-2b in patients with chronic hepatitis B who previously failed interferon therapy [abstract no. 901]. Hepatology 1998 Oct; 28 (4 Pt 2): 388aGoogle Scholar
  103. 103.
    Schalm SW, Heathcote J, Cianciara J, et al. Lamivudine and alpha interferon combination treatment of patients with chronic hepatitis B infection: a randomised trial. Gut 2000; 46: 562–8PubMedCrossRefGoogle Scholar
  104. 104.
    Suzuki Y, Kumada H, Ikeda K, et al. Histological changes in liver biopsies after one year of lamivudine treatment in patients with chronic hepatitis B infection. J Hepatol 1999; 30: 743–8PubMedCrossRefGoogle Scholar
  105. 105.
    Leung N, Wu PC, Tsang S, et al. Continued histological improvement in Chinese patients with chronic hepatitis B with 2 years lamivudine [abstract no. 1307]. Hepatology 1998 Oct; 28 (4 Pt 2): 489AGoogle Scholar
  106. 106.
    Schiff ER, Heathcote J, Dienstag JL, et al. Improvements in liver histology and cirrhosis with extended lamivudine therapy [abstract no. 546]. Hepatology 2000 Oct; 32 (4 Pt 2): 296AGoogle Scholar
  107. 107.
    Tassopoulos NC, Anagnostopoulos GD, Delladetsima JK, et al. Extended lamivudine treatment in patients with HBeAg negative/HBVDNA positive chronic hepatitis B (CHB) [abstract no. 1187]. Hepatology 2000 Oct; 32 (4 Pt 2): 456Google Scholar
  108. 108.
    Liaw Y-F, Leung NWY, Chang T-T, et al. Effects of extended lamivudine therapy in Asian patients with chronic hepatitis B. Gastroenterology 2000 Jul; 119(1): 172–80PubMedCrossRefGoogle Scholar
  109. 109.
    Santantonio T, Mazzola M, Iacovazzi T, et al. Long-term follow-up of patients with anti-HBe/HBV DNA-positive chronic hepatitis B treated for 12 months with lamivudine. J Hepatol 2000 Feb; 32: 300–6PubMedCrossRefGoogle Scholar
  110. 110.
    Hadziyannis SJ, Papatheodoridis GV, Dimou E, et al. Efficacy of long-term lamivudine monotherapy in patients with hepatitis B e antigen—negative chronic hepatitis B. Hepatology 2000 Oct; 32(4): 847–51PubMedCrossRefGoogle Scholar
  111. 111.
    Leung NWY, Lai CL, Chang TT, et al. Three year lamivudine therapy in chronic HBV [abstract no. GS5/25]. J Hepatol 1999; 30 Suppl. 1: 59Google Scholar
  112. 112.
    Chang TT, Lai CL, Liaw YF, et al. Incremental increases in HBeAg seroconversion and continued ALT normalization in Asian chronic HBV (CHB) patients treated with lamivudine for four years [abstract no. 077]. Antiviral Ther 2000; 5 Suppl. 1: 44Google Scholar
  113. 113.
    Schiff E, Cianciara J, Kowdley K, et al. Durability of HBeAG seroconversion after lamivudine monotherapy in controlled phase II and III trials [abstract no. 1]. Hepatology 1998 Oct; 28 (4 Pt 2): 163AGoogle Scholar
  114. 114.
    Dienstag JL, Schiff ER, Mitchell M, et al. Extended lamivudine retreatment for chronic hepatitis B: maintenance of viral suppression after discontinuation of therapy. Hepatology 1999 Oct; 30: 1082–7PubMedCrossRefGoogle Scholar
  115. 115.
    Guan R, Liaw YF, Leung NWY, et al. Durable HBeAg response in Chinese patients treated with lamivudine [abstract no. PP-2]. J Gastroenterol Hepatol 2000 Sep; 15 Suppl.: I106CrossRefGoogle Scholar
  116. 116.
    Hong SP, Han K-H, Ahn SH, et al. Long-term effect of lamivudine treatment in patients with chronic hepatitis B: efficacy and durability of response after cessation of treatment [abstract no. 1712]. Hepatology 2000 Oct; 32 (4 Pt 2): 587ACrossRefGoogle Scholar
  117. 117.
    Schiff ER, Cianciara J, Willems B, et al. Durability of HBeAG responses to lamivudine and interferon in the early post-treatment period in adults with chronic hepatitis B [abstract no. 872]. Hepatology 2000 Oct; 32 (4 Pt 2): 377AGoogle Scholar
  118. 118.
    Schiff E, Cianciara J, Karayalcin S, et al. Durable HBeAg and HBsAg seroconversions after lamivudine for chronic hepatitis B (CHB) [abstract no. P/C06/12]. J Hepatol 2000; 32 Suppl. 2: 99CrossRefGoogle Scholar
  119. 119.
    Song B-C, Suh DJ, Lee HC, et al. Hepatitis B e antigen seroconversion after lamivudine therapy is not durable in patients with chronic hepatitis B in Korea. Hepatology 2000 Oct; 32(4): 803–6PubMedCrossRefGoogle Scholar
  120. 120.
    Chien R-N, Liaw Y-F, Atkins M, et al. Pretherapy alanine transaminase level as a determinant for hepatitis B e antigen seroconversion during lamivudine therapy in patients with chronic hepatitis B. Hepatology 1999 Sep; 30: 770–4PubMedCrossRefGoogle Scholar
  121. 121.
    Chang T-T, Lai CL, Liaw Y-F, et al. Enhanced HBEAG Seroconversion rates in Chinese patients on lamivudine [abstract no. 1038]. Hepatology 1999 Oct; 30 (4 Pt 2): 420AGoogle Scholar
  122. 122.
    Liaw Y-F, Tsai S-L, Chien R-N, et al. Prednisolone priming enhances Th1 response and efficacy of subsequent lamivudine therapy in patients with chronic hepatitis B. Hepatology 2000 Sep; 32(3): 604–9PubMedCrossRefGoogle Scholar
  123. 123.
    Perrillo RP. Short-term corticosteroid therapy in combination with lamivudine: a case of déjà vu? [Editorial]. Hepatology 2000 Sep; 32(3): 663–5PubMedCrossRefGoogle Scholar
  124. 124.
    Villeneuve J-P, Condreay LD, Willems B, et al. Lamivudine treatment for decompensated cirrhosis resulting from chronic hepatitis B. Hepatology 2000 Jan; 31: 207–10PubMedCrossRefGoogle Scholar
  125. 125.
    Yao FY, Bass NM. Lamivudine treatment in patients with severely decompensated cirrhosis due to replicating hepatitis B infection. J Hepatol 2000; 33: 301–7PubMedCrossRefGoogle Scholar
  126. 126.
    Kapoor D, Guptan RC, Wakil SM, et al. Beneficial effects of lamivudine in hepatitis B virus-related decompensated cirrhosis. J Hepatol 2000; 33: 308–12PubMedCrossRefGoogle Scholar
  127. 127.
    Sponseller CA, Bacon BR, Di Bisceglie AM. Clinical improvement in patients with decompensated liver disease caused by hepatitis B after treatment with lamivudine. Liver Transpl 2000 Nov; 6(6): 715–20PubMedCrossRefGoogle Scholar
  128. 128.
    Yao FYK, Terrault NA, Friese CE, et al. Lamivudine reduces the need for liver transplantation and improves survival in patients with severely decompensated cirrhosis due to active hepatitis B infection: a controlled study [abstract no. 1190]. Hepatology 2000 Oct; 32 (4 Pt 2): 457AGoogle Scholar
  129. 129.
    Lampertico P, Iavarone M, Romeo R, et al. Long-term lamivudine therapy improves Child-Pugh score in patients with hepatitis B-related cirrhosis [abstract no. 1195]. Hepatology 2000 Oct; 32 (4 Pt 2): 457Google Scholar
  130. 130.
    Hann H-WL, Fontana RJ, Wright T, et al. Lamivudinetreatment for decompensated cirrhosis due to hepatitis B: a multicenter longitudinal study [abstract no. 2347]. Gastroenterology 2000 Apr; 118 (4 Pt 1): A1004CrossRefGoogle Scholar
  131. 131.
    Angelico M, Di Paulo D, Palmieri G, et al. Lamivudine improves the Child-Pugh score in HbsAg positive patients listed for transplantation: a single center experience [abstract no. P/C06/31]. J Hepatol 2000; 32 Suppl. 2: 104CrossRefGoogle Scholar
  132. 132.
    Gao BJ, Xie HS, Lu Z. Lamivudine therapy of decompensated chronic hepatitis B [abstract no. P-H-2]. J Gastroenterol Hepatol 2000 Sep; 15 Suppl: I184Google Scholar
  133. 133.
    Fontana R, Hann H-W, Wright T, et al. Lamivudine treatment of chronic hepatitis B liver transplant candidates: a multi-centre, prospective US study [abstract no. 058]. 10th International Symposium on Viral Hepatitis and Liver Disease; 2000 Apr 9–13; Atlanta, 33Google Scholar
  134. 134.
    Lim SG, Lo SK, Chong J, et al. Outcome of treatment with lamivudine for chronic hepatitis B in a compassionate care program in Asia [abstract]. Hepatology 1999 Oct; 30 (4 Pt 2): 643Google Scholar
  135. 135.
    Perrillo RP, Wright T, Rakela J, et al. A multicenter United States—Canadian trial to assess lamivudine monotherapy before and after liver transplantation for chronic hepatitis B. Hepatology 2001 Feb; 33(2): 424–32PubMedCrossRefGoogle Scholar
  136. 136.
    Jung SA, Chung Y-H, Yang SH, et al. Efficacy and safety of lamivudine therapy in patients with decompensated liver cirrhosis caused by HBV infection [abstract]. Hepatology 1999 Oct; 30 (4 Pt 2): 645AGoogle Scholar
  137. 137.
    Fontana RJ, Lok ASF. Lamivudine treatment in patients with decompensated hepatitis B cirrhosis: for whom and when? J Hepatol 2000 (33): 329–32PubMedCrossRefGoogle Scholar
  138. 138.
    Fontana RJ, Keeffe EB, Soldevila C, et al. Is lamivudine beneficial in HBsAG+ patients awaiting liver transplantation? Experience in 182 North American patients [abstract no. 40]. Transplantation 1999 Apr 15; 67: S16CrossRefGoogle Scholar
  139. 139.
    Fontana RJ, Perrillo R, Hann H-WL, et al. Determinants of survival in 133 patients with decompensated chronic hepatitis B treated with lamivudine [abstract no. 239]. Hepatology 2000 Oct; 32 (4 Pt 2): 221AGoogle Scholar
  140. 140.
    Cotrina M, Buti M, Jardi R, et al. Prediction of long-term response to lamivudine by measuring HBV-DNA levels at month 3 in patients with chronic hepatitis B [abstract no. 1711]. Hepatology 2000 Oct; 32 (4 Pt 2): 587ACrossRefGoogle Scholar
  141. 141.
    Lau DT-Y, Khokhar F, Doo E, et al. Long-term therapy of chronic hepatitis B with lamivudine. Hepatology 2000 Oct; 32: 828–34PubMedCrossRefGoogle Scholar
  142. 142.
    Ono SK, Kato N, Shiratori Y, et al. The polymerase L528M mutation cooperates with nucleotide binding-site mutations, increasing hepatitis B virus replication and drug resistance. J Clin Invest 2001 Feb; 107(4): 449–55PubMedCrossRefGoogle Scholar
  143. 143.
    Liaw Y-F, Chien R-N, Yeh C-T, et al. Acute exacerbation and hepatitis B virus clearance after emergence of YMDD motif mutation during lamivudine therapy [see comments]. Hepatology 1999 Aug; 30: 567–72PubMedCrossRefGoogle Scholar
  144. 144.
    Chang TT, Lai CL, Ng KY, et al. Enhanced HBeAg and ALT responses during long term lamivudine treatment in Chinese patients [abstract no. O-H-21]. J Gastroenterol Hepatol 2000 Sep; 15 Suppl.: I134CrossRefGoogle Scholar
  145. 145.
    Lok AS-F, Hussain M, Cursano C, et al. Evolution of hepatitis B virus polymerase gene mutations in hepatitis B e antigennegative patients receiving lamivudine therapy. Hepatology 2000 Nov; 32(5): 1145–53PubMedCrossRefGoogle Scholar
  146. 146.
    Lok ASF. Lamivudine therapy for chronic hepatitis B: is longer duration of treatment better? [editorial]. Gastroenterology 2000 Jul; 119(1): 263–6PubMedCrossRefGoogle Scholar
  147. 147.
    Shaw T, Locarnini S. Combination chemotherapy for hepatitis B virus: the final solution? [editorial]. Hepatology 2000 Aug; 32(2): 430–2PubMedCrossRefGoogle Scholar
  148. 148.
    Shaw T, Locarnini S. Combination chemotherapy for hepatitis B virus: the path forward? Drugs 2000 Sep; 60(3): 517–31PubMedCrossRefGoogle Scholar
  149. 149.
    Honkoop P, de Man RA, Niesters HGM, et al. Acute exacerbation of chronic hepatitis B virus infection after withdrawal of lamivudine therapy. Hepatology 2000 Sep; 32(3): 635–9PubMedCrossRefGoogle Scholar
  150. 150.
    Crowley SJ, Tognarini D, Desmond P. The cost-effectiveness of the introduction of lamivudine for the treatment of chronic hepatitis B in Australia [abstract]. Hepatology 1999 Oct; 30 (4 Pt 2): 181AGoogle Scholar
  151. 151.
    Desmond P, Tognarini D, Crowley SJ. The potential impact of lamivudine (100 mg) on the clinical management of chronic hepatitis B in Australia [abstract]. Hepatology 1999 Oct; 30 (4 Pt 2): 643AGoogle Scholar
  152. 152.
    Bonzanini A, Gianfrate F, Lloyd A, et al. Adrug budget perspective of lamivudine compared with interferon-α in the treatment of precore chronic hepatitis B in Italy [abstract no. P/C06/49]. J Hepatol 2000; 32 Suppl. 2: 109CrossRefGoogle Scholar
  153. 153.
    Zacks SL, Fried MW. Cost comparison of interferon and lamivudine for the treatment of chronic hepatitis B [abstract no. 1289]. Hepatology 1999 Oct; 30 (4 Pt 2) Suppl.: 483AGoogle Scholar
  154. 154.
    Lacey LF, Cox FM, Payne SL. A drug budget perspective of lamivudine compared with interferon-α in the treatment of chronic hepatitis B in the United States [abstract]. Hepatology 1999 Oct; 30 (4 Pt 2): 481AGoogle Scholar
  155. 155.
    Dickens T, Raasch RH, Saal GB, et al. The long-term cost-effectiveness of lamivudine for the treatment of chronic hepatitis B in the United States [abstract no. 1722]. Hepatology 2000 Oct; 32 (4 Pt 2): 590AGoogle Scholar
  156. 156.
    Dickens T, Raasch RH, Saal GB, et al. The short-term costeffectiveness of lamivudine for the treatment of chronic hepatitis B in the United States [abstract no. 1721]. Hepatology 2000 Sep; 32 (4 Pt 2): 590AGoogle Scholar
  157. 157.
    Lau GKK, Tsiang M, Hou J, et al. Combination therapy with lamivudine and famciclovir for chronic hepatitis Binfected Chinese patients: a viral dynamics study. Hepatology 2000 Aug; 32(2): 394–9PubMedCrossRefGoogle Scholar
  158. 158.
    Kwo PY, Chalasani N, Lumeng L, et al. A pilot study with lamivudine and famciclovir for the treatment of chronic hepatitis B [abstract no. 1717]. Hepatology 2000 Oct; 32 (4 Pt 2): 589Google Scholar
  159. 159.
    Naoumov NV, Suri D, Rigopoulou EI, et al. Combination treatment with lamivudine plus interleukin-12 shows greater antiviral activity in chronic hepatitis B [abstract no. 868]. Hepatology 2000 Oct; 32 (4 Pt 2): 376Google Scholar
  160. 160.
    Lin BL, Yang SY, Huang GU, et al. A study on the short-term efficacy of thymosin α1 (Tα1) combined with lamivudine in treating patients with chronic hepatitis B [abstract no. O-H-20]. J Gastroenterol Hepatol 2000 Sep; 15 Suppl.: I133CrossRefGoogle Scholar
  161. 161.
    Farrell GC. Immunosuppression and reactivation of hepatitis B in the lamivudine era: opportunities for prevention and exploitation? [editorial]. J Gastroenterol Hepatol 1999; 14: 741–4PubMedCrossRefGoogle Scholar
  162. 162.
    Pianko S, McHutchison J. Chronic hepatitis B: new therapies on the horizon? [commentary]. Lancet 1999 Nov 13; 354: 1662–3PubMedCrossRefGoogle Scholar
  163. 163.
    Farrell GC. Clinical potential of emerging new agents in hepatitis B. Drugs 2000 Oct; 60(4): 701–10PubMedCrossRefGoogle Scholar

Copyright information

© Adis International Limited 2001

Authors and Affiliations

  1. 1.Adis International LimitedMairangi Bay, Auckland 10New Zealand

Personalised recommendations