Manejo de pacientes con infección crónica por el virus de la hepatitis B

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1 Manejo de pacientes con infección crónica por el virus de la hepatitis B Referencias 1. Lee WM. Hepatitis B virus infection. N Engl J Med 1997; 337: Maddrey WC. Hepatitis B: an important public health issue. J Med Virol 2000; 61: Kane M. Global programme for control of hepatitis B infection. Vaccine 1995; 13: S Lok AS, Heathcote EJ, Hoofnagle JH. Management of hepatitis B: 2000 summary of a workshop. Gastroenterology 2001; 120: Anon. EASL International Consensus Conference on hepatitis B. J Hepatol 2003; 39 (suppl 1): S Papatheodoridis GV, Hadziyannis SJ. Current management of chronic hepatitis B. Aliment Pharmacol Ther 2004; 19: Hadziyannis SJ, Papatheodoridis GV. Emerging treatments in chronic hepatitis B. Expert Opin Emerg Drugs 2004; 9: Lok ASF, McMahon BJ. Chronic hepatitis B. Hepatology 2007; 45: Fattovich G. Natural history and prognosis of hepatitis B. Semin Liver Dis 2003; 23: McMahon BJ. The natural history of chronic hepatitis B virus infection. Semin Liver Dis 2004; 24 (suppl 1): Hadziyannis SJ, Papatheodoridis GV. Hepatitis Be antigen negative chronic hepatitis B natural history and treatment. Semin Liver Dis 2006; 26: Hoofnagle JH, Dusheiko GM, Seeff LB, Jones A, Waggoner JG, Bales ZB. Seroconversion from hepatitis B e antigen to antibody in chronic type B hepatitis. Ann Intern Med 1981; 94: Fattovich G, Rugge M, Brollo L, et al. Clinical, virologic and histologic outcome following seroconversion from HBeAg to anti-hbe in chronic hepatitis type B. Hepatology 1986; 6: Lok AS, Lai CL, Wu PC, Leung EK, Lam TS. Spontaneous hepatitis B e antigen to antibody seroconversion and reversion in Chinese patients with chronic hepatitis B virus infection. Gastroenterology 1987; 92: Chu CJ, Hussain M, Lok AS. Hepatitis B virus genotype B is associated with earlier HBeAg seroconversion compared with hepatitis B virus genotype C. Gastroenterology 2002; 122: Yuen MF, Sablon E, Yuan HJ, et al. Signifi cance of hepatitis B genotype in acute exacerbation, HBeAg seroconversion, cirrhosis-related complications, and hepatocellular carcinoma. Hepatology 2003; 37: Chu CJ, Keeff e EB, Han SH, et al. Hepatitis B virus genotypes in the United States: results of a nationwide study. Gastroenterology 2003; 125: Papatheodoridis GV, Hadziyannis SJ. Diagnosis and management of pre-core mutant chronic hepatitis B. J Viral Hepat 2001; 8: Hadziyannis SJ, Vassilopoulos D. Hepatitis B e antigen-negative chronic hepatitis B. Hepatology 2001; 34: Brunetto MR, Giarin M, Oliveri F, et al. Wild type and e antigen-minus hepatitis B virus in course of chronic hepatitis. Proc Natl Acad Sci USA 1991; 88: Lai ME, Solinas A, Mazzoleni AP, et al. The role of pre-core hepatitis B virus mutants on the long-term outcome of chronic hepatitis B virus hepatitis. A longitudinal study. J Hepatol 1994; 20: Liaw YF, Tai DI, Chu CM, Chen TJ. The development of cirrhosis in patients with chronic type B hepatitis: a prospective study. Hepatology 1988; 8: Fattovich G, Brollo L, Giustina G, et al. Natural-history and prognostic factors for chronic hepatitis type B. Gut 1991; 32:

2 24. Weissberg JI, Andres LL, Smith CI, et al. Survival in chronic hepatitis B. An analysis of 379 patients. Ann Intern Med 1984; 101: Realdi G, Fattovich G, Hadziyannis S, et al. Survival and prognostic factors in 366 patients with compensated cirrhosis type B: a 26. multicenter study. J Hepatol 1994; 21: de Jongh FE, Janssen HL, de Man RA, Hop WC, Schalm SW, van Blankenstein M. Survival and prognostic indicators in HBsAg-positive cirrhosis of the liver. Gastroenterology 1992;103: Beasley RP. The major etiology of hepatocellular carcinoma. Cancer 1988; 61: 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: Liaw YF, Leung N, Guan R, et al. Asian-Pacifi c consensus statement on the management of chronic hepatitis B: a 2005 update. Liver Int 2005; 25: de Franchis R, Meucci G, Vecchi M, et al. The natural history of asymptomatic hepatitis B surface antigen carriers. Ann Intern Med 1993; 118: Keeff e EB, Dieterich DT, Han S-HB, et al. A treatment algorithm for the management of chronic hepatitis B virus infection in the United States: an update. Clin Gastroenterol Hepatol 2006; 4: Manesis E, Papatheodoridis GV, Sevastianos V, Cholongitas E, Papaioannou C, Hadziyannis SJ. Signifi cance of hepatitis B viremia levels determined by a quantitative polymerase chain reaction assay in patients with HBeAg-negative chronic hepatitis B virus infection. Am J Gastroenterol 2003; 98: 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: Papatheodoridis GV, Manesis EK, Manolakopoulos S, et al. Is there a meaningful serum HBV DNA cut-off level for therapeutic decisions in HBeAg-negative chronic hepatitis B (CHBe )? Hepatology 2006; 44 (suppl 1): 541A (abstr). 36. Zoulim F. Mechanism of viral persistence and resistance to nucleoside and nucleotide analogs in chronic hepatitis B virus infection. Antiviral Res 2004; 64: Werle-Lapostolle B, Bowden S, Locarnini S, et al. Persistence of cccdna during the natural history of chronic hepatitis B and decline during adefovir dipivoxil therapy. Gastroenterology 2004; 126: Sung JJ, Wong ML, Bowden S, et al. Intrahepatic hepatitis B virus covalently closed circular DNA can be a predictor of sustained response to therapy. Gastroenterology 2005; 128: Zoulim F. Antiviral therapy of chronic hepatitis B: can we clear the virus and prevent drug resistance? Antivir Chem Chemother 2004;15: 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: Korenman J, Baker B, Waggoner J, Everhart JE, Di Bisceglie AM, Hoofnagle JH. Longterm remission of chronic hepatitis B after alpha-interferon therapy. Ann Intern Med 1991; 114: Fattovich G, Giustina G, Realdi G, Corrocher R, Schalm SW. Long-term outcome of hepatitis B e antigen-positive patients with compensated cirrhosis treated with interferon alfa. European Concerted Action on Viral Hepatitis (EUROHEP). Hepatology 1997;26: Van Zonneveld M, Honkoop P, Hansen BE, et al. Long-term follow-up of alphainterferon treatment of patients with chronic hepatitis B. Hepatology 2004; 39: Papatheodoridis GV, Manesis E, Hadziyannis SJ. The long-term outcome of interferon-α treated and untreated patients with HBeAg-negative chronic hepatitis B. J Hepatol 2001; 34: Papatheodoridis GV, Dimou E, Dimakopoulos K, et al. Outcome of hepatitis B e antigennegative chronic hepatitis B on long-term nucleos(t)ide analog therapy starting with lamivudine. Hepatology 2005; 42:

3 46. Lin S-M, Sheen I-S, Chien R-N, Chu C-M, Liaw Y-F. Long-term benefi cial eff ect of interferon therapy in patients with chronic hepatitis B virus infection. Hepatology 1999; 29: 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: Yuen MF, Hui CK, Cheng CC, Wu CH, Lai YP, Lai CL. Long-term follow-up of interferon alfa treatment in Chinese patients with chronic hepatitis B infection: the eff ect on hepatitis B e antigen seroconversion and the development of cirrhosis-related complications. Hepatology 2001; 34: Yuan HJ, Yuen MF, Ka-Ho WD, Sablon E, Lai CL. The relationship between HBV-DNA levels and cirrhosis-related complications in Chinese with chronic hepatitis B. J Viral Hepat 2005; 12: Lok AS, McMahon BJ. Chronic hepatitis B: update of recommendations. Hepatology 2004; 39: Locarnini S, Hatzakis A, Heathcote J, et al. Management of antiviral resistance in patients with chronic hepatitis B. Antivir Ther 2004; 9: Hoofnagle JH, Di Bisceglie AM. The treatment of chronic viral hepatitis. N Engl J Med 1997; 336: Papatheodoridis GV, Dimou E, Papadimitropoulos V. Nucleoside analogues for chronic hepatitis B: antiviral effi cacy and viral resistance. Am J Gastroenterol 2002; 97: Wong DK, Cheung AM, O Rourke K, Naylor CD, Detsky AS, Heathcote J. Eff ect of alphainterferon in patients with hepatitis B e antigen-positive chronic hepatitis B. A meta-analysis. Ann Intern Med 1993; 119: Lau GKK, 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: 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: 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: Marcellin P, Chang TT, Lim SG, et al. Adefovir dipivoxil for the treatment of hepatitis B antigen-positive chronic hepatitis B.N Engl J Med 2003; 348: 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: Lai C-L, Gane E, Liaw Y-F, et al. Telbivudine (LdT) vs lamivudine for chronic hepatitis B: fi rst-year results from the international phase III GLOBE trial. Hepatology 2005; 42 (suppl 1): 748A (abstr). 61. Manesis EK, Hadziyannis SJ. Interferon-alpha treatment and retreatment of hepatitis B e antigen-negative chronic hepatitis B.Gastroenterology 2001; 121: Lampertico P, Del Ninno E, Vigano M, et al. Long-term suppression of hepatitis B e antigen-negative chronic hepatitis B by 24-month interferon therapy. Hepatology 2003; 37: 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: Marcellin P, Bonino F, Lau GK, et al. Factors associated with sustained virologic response 1 year after treatment with peginterferon alfa-2a (40KD) (Pegasys) monotherapy for HBeAg-negative chronic hepatitis B. Hepatology 2005; 42 (suppl 1): 580A (abstr). 65. Tassopoulos NC, Volpes R, Pastore G, et al. Effi cacy of lamivudine in patients with hepatitis B e antigen-negative/hepatitis B virus DNA-positive (precore mutant) chronic hepatitis B. Hepatology 1999; 29: Tassopoulos NC, Volpes R, Pastore G, et al. Post lamivudine treatment follow up of patients with HBeAg negative chronic hepatitis B. J Hepatol 1999; 30 (suppl 1): 117 (abstr). 67. Santantonio T, Mazzola M, Iacovazzi T, Miglietta A, Guastadisegni A, Pastore G. Longterm follow-up of patients with anti-hbe/hbv DNA-positive chronic hepatitis B treated for 12 months with lamivudine. J Hepatol 2000; 32:

4 68. Hadziyannis SJ, Tassopoulos NC, Heathcote EJ, et al. Adefovir dipivoxil for the treatment of hepatitis B antigen-negative chronic hepatitis B. N Engl J Med 2003; 348: Hadziyannis SJ, Tassopoulos NC, Heathcote EJ, et al. Long-term therapy with adefovir dipivoxil for HBeAg-negative chronic hepatitis B. N Engl J Med 2005; 352: Lai CL, Shouval D, Lok AS, et al. Entecavir versus lamivudine for patients with HBeAgnegative chronic hepatitis B. N Engl J Med 2006; 354: Liaw Y-F, Leung NW, Chang T-T, et al. Eff ects of extended lamivudine therapy in Asian patients with chronic hepatitis B. Gastroenterology 2000; 119: Lok AS, Lai CL, Leung N, et al. Long-term safety of lamivudine treatment in patients with chronic hepatitis B. Gastroenterology 2003; 125: Leung NW, Lai CL, Chang TT, et al. Extended lamivudine treatment in patients with chronic hepatitis B enhances hepatitis B e antigen seroconversion rates: results after 3 years of therapy. Hepatology 2001; 33: Chang TT, Lai CL, Chien RN, et al. Four years of lamivudine treatment in Chinese patients with chronic hepatitis B. J Gastroenterol Hepatol 2004; 19: Marcellin P, Chang T, Lim S, et al. Increasing serologic, virologic and biochemical response over time to adefovir dipivoxil (ADV) 10 mg in HBeAg+ chronic hepatitis B (CHB) patients. J Hepatol 2005; 42 (suppl 2): (abstr). 76. Gish RG, Chang TT, de Man RA, et al. Entecavir results in substantial virologic and biochemical improvement and HBeAg seroconversion through 96 weeks of treatment in HBeAg(+) chronic hepatitis B patients (study ETV-022). Hepatology 2005; 42 (suppl 1):267A (abstr). 77. Chang TT, Chao Y-C, Kayamakoglou S, et al. Entecavir maintained virologic suppression through 3 years of treatment in antiviral naïve HBeAg(+) patients (ETV022/901). Hepatology 2006; 44 (suppl 1): 229A (abstr). 78. Lai C-L, Gane E, Hsu C-W, et al. Two-years results from the GLOBE trial in patients with hepatitis B: greater clinical and antiviral effi cacy for telbivudine (LdT) vs lamivudine. Hepatology 2006;44 (suppl 1): 222A (abstr). 79. Papatheodoridis GV, Dimou E, Laras A, Papadimitropoulos V, Hadziyannis SJ. Course of virologic breakthroughs under long-term lamivudine in HBeAg-negative precore mutant HBV liver disease. Hepatology 2002; 36: Gaia S, Marzano A, Smedile A, et al. Four years of treatment with lamivudine: clinical and virological evaluations in HBe antigen-negative chronic hepatitis B. Aliment Pharmacol Ther 2004; 20: Di Marco V, Marzano A, Lampertico P, et al. Clinical outcome of HBeAg-negative chronic hepatitis B in relation to virological response to lamivudine. Hepatology 2004; 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: Janssen HL, van Zonneveld M, Senturk H, et al. Pegylated interferon alfa-2b alone or in combination with lamivudine for HBeAg-positive chronic hepatitis B: a randomised trial. Lancet 2005; 365: Chan HL, Leung NW, Hui AY, et al. A randomized, controlled trial of combination therapy for chronic hepatitis B: comparing pegylated interferon-alpha2b and lamivudine with lamivudine alone. Ann Intern Med 2005; 142: Lai C-L, Leung N, Teo E-K, et al. A 1-year trial of telbivudine, lamivudine, and the combination in patients with hepatitis B e antigen-positive chronic hepatitis B. Gastroenterology 2005; 129: van Nunen AB, Hansen BE, Suh DJ, et al. Durability of HBeAg seroconversion following antiviral therapy for chronic hepatitis B: relation to type of therapy and pretreatment serum hepatitis B virus DNA and alanine aminotransferase. Gut 2003; 52: Dienstag JL, Cianciara J, Karayalcin S, et al. Durability of serologic response after lamivudine treatment of chronic hepatitis B. Hepatology 2003; 37:

5 88. Song B-C, Suh DJ, Lee HC, Chung Y-H, Lee YS. Hepatitis B e antigen seroconversion after lamivudine therapy is not durable in patients with chronic hepatitis B in Korea. Hepatology 2000; 32: Lee KM, Cho SW, Kim SW, Kim HJ, Hahm KB, Kim JH. Effect of virological response on post-treatment durability of lamivudine-induced HBeAg seroconversion. J Viral Hepat 2002; 9: Borroto-Esoda K, Arterburn S, Snow A, et al. Final analysis of virological outcomes and resistance during 5 years of adefovir dipivoxil monotherapy in HBeAg-negative patients. Gastroenterology 2006; 130 (suppl 2): A (abstr). 91. Poynard T, Chutaputti A, Hwang SG, et al. Sustained off treatment HBeAg response in telbivudine and lamivudine treated HBeAg-positive patients from the GLOBE study. J Hepatol 2007;46 (suppl 1): S27 (abstr). 92. Marcellin P, Bonino F, Lau GK, et al. Virological and biochemical response in patients with HBeAg-negative CHB treated with peginterferon alfa-2a (40KD) } lamivudine: 3-year follow-up results. J Hepatol 2007; 46 (suppl 1): S25 26 (abstr). 93. Hadziyannis SJ, Papatheodoridis GV, Dimou E, Laras A, Papaioannou C. Effi cacy of long-term lamivudine monotherapy in patients with HBeAg negative chronic hepatitis B. Hepatology 2000;32: Poordad F, Dieterich DT, Min AD, et al. Continued virologic improvement through 96 weeks of entecavir treatment in HBeAg( ) chronic hepatitis B patients (Study ETV-027). Gastroenterology 2006; 130 (suppl 2): A848 (abstr). 95. Fung SK, Wong F, Hussain M, Lok AS. Sustained response after a 2-year course of lamivudine treatment of hepatitis B e antigen-negative chronic hepatitis B. J Viral Hepat 2004; 11: Barbon V, Gaia S, Marzano A, Lagget M, Rizzetto M. Prompt relapse of viremia after lamivudine discontinuation in e-minus chronic hepatitis B patients completely responders during 5 years of therapy. J Hepatol 2004; 41: Hadziyannis SJ, Sevastianos V, Rapti IN, Tassopoulos N. Sustained biochemical and virological remission after discontiuation of 4 to 5 years of adefovir dipivoxil (ADV) treatment in HBeAg-negative chronic hepatitis B. Hepatology 2006; 44 (suppl 1): 231A 232A (abstr). 98. 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: Shaw T, Bartholomeusz A, Locarnini S. HBV drug resistance: mechanisms, detection and interpretation. J Hepatol 2006; 44: Nowak MA, Bonhoeff er S, Hill AM, Boehme R, Thomas HC, McDade H. Viral dynamics in hepatitis B virus infection. Proc Natl Acad Sci USA 1996; 93: Girones R, Miller RH. Mutation rate of the hepadnavirus genome. Virology 1989; 170: Kobayashi S, Ide T, Sata M. Detection of YMDD motif mutations in some lamivudineuntreated asymptomatic hepatitis B virus carriers. J Hepatol 2001; 34: Paik YH, Chung HY, Ryu W-S, et al. Emergence of YMDD motif mutant of hepatitis B virus during short-term lamivudine therapy in South Korea. J Hepatol 2001; 35: Alexopoulou A, Karayiannis P, Hadziyannis SJ, Aiba N, Thomas HC. Emergence and selection of HBV variants in an anti-hbe positive patient persistently infected with quasi-species. J Hepatol 1997; 26: Cane PA, Mutimer D, Ratcliff e D, et al. Analysis of hepatitis B virus quasispecies changes during emergence and reversion of lamivudine resistance in liver transplantation. Antivir Ther 1999; 4: Hunt CM, McGill JM, Allen ML, Condreay LD. Clinical relevance of hepatitis B virus mutations. Hepatology 2000; 31: Dienstag JL, Goldin RD, Heathcote EJ, et al. Histologic outcome during long-term lamivudine therapy. Gastroenterology 2003; 124: Manolakopoulos S, Karatapanis S, Elefsiniotis J, et al. Clinical course of lamivudine monotherapy in patients with decompensated cirrhosis due to HBeAg negative chronic HBV infection.am J Gastroenterol 2004; 99:

6 109. Villeneuve JP, Condreay LD, Willems B, et al. Lamivudine treatment for decompensated cirrhosis resulting from chronic hepatitis B. Hepatology 2000; 31: Fung SK, Andreone P, Han SH, et al. Adefovir-resistant hepatitis B can be associated with viral rebound and hepatic decompensation. J Hepatol 2005; 43: Allen MI, Deslauriers M, Andrews CW, et al. Identifi cation and characterization of mutations in hepatitis B virus resistant to lamivudine. Lamivudine Clinical Investigation Group. Hepatology 1998; 27: Bartholomeusz A, Locarnini S. Hepatitis B virus mutations associated with antiviral therapy. J Med Virol 2006; 78 (suppl 1):S Yuen MF, Sablon E, Hui CK, Yuan HJ, Decraemer H, Lai CL. Factors associated with hepatitis B virus DNA breakthrough in patients receiving prolonged lamivudine therapy. Hepatology 2001; 34: Manolakopoulos S, Bethanis S, Elefsiniotis J, et al. Lamivudine monotherapy in HBeAgnegative chronic hepatitis B: prediction of response-breakthrough and long-term clinical outcome. Aliment Pharmacol Ther 2006; 23: Angus P, Vaughan R, Xiong S, et al. Resistance to adefovir dipivoxil therapy associated with the selection of a novel mutation in the HBV polymerase. Gastroenterology 2003; 125: Colonno RJ, Rose R, Baldick CJ, et al. Entecavir resistance is rare in nucleoside naive patients with hepatitis B. Hepatology 2006; 44: Colonno RJ, Rose RE, Pokornowski K, Baldick CJ, Klesczewski K, Tenney D. Assessment at three years shows high barrier to resistance is maintained in entecavir-treated naive patients while resistance emergence increases over time in lamivudine refractory patients. Hepatology 2006; 44 (suppl 1): 229A 30A (abstr) Colonno RJ, Rose RE, Pokornowski K, et al. Four year assessment of ETV resistance in nucleoside-naive and lamivudine refractory patients. J Hepatol 2007; 46 (suppl 1): S294 (abstr) Tenney DJ, Levine SM, Rose RE, et al. Clinical emergence of entecavir-resistant hepatitis B virus requires additional substitutions in virus already resistant to lamivudine. Antimicrob Agents Chemother 2004; 48: Di Bisceglie A, Lai C-L, Gane E, et al. Telbivudine GLOBE trial: Maximal early HBV suppression is predictive of optimal two-year effi cacy in nucleoside-treated hepatitis B patients. Hepatology 2006;44 (suppl 1): 230A 31A (abstr) Carreno V, Marcellin P, Hadziyannis S, et al. Retreatment of chronic hepatitis B e antigen-positive patients with recombinant interferon alfa-2a. The European Concerted Action on Viral Hepatitis (EUROHEP). Hepatology 1999; 30: Honkoop P, de Man RA, Niesters HG, Zondervan PE, Schalm SW. Acute exacerbation of chronic hepatitis B virus infection after withdrawal of lamivudine therapy. Hepatology 2000; 32: Fung SK, Chae HB, Fontana RJ, et al. Virologic response and resistance to adefovir in patients with chronic hepatitis B. J Hepatol 2006; 44: Grim SA, Romanelli F. Tenofovir disoproxil fumarate. Ann Pharmacother 2003; 37: Van Bommel F, Zollner B, Sarrazin C, et al. Tenofovir for patients with lamivudine resistant hepatitis B virus (HBV) infection and high HDV DNA level during adefovir therapy. Hepatology 2006; 44: Yang H, Qi X, Sabogal A, Miller M, Xiong S, Delaney WE.Cross-resistance testing of next-generation nucleosite and nucleotide analogues against lamivudine-resistant HBV. Antivir Ther 2005; 10: Dusheiko G, Bertoletti A. Resistance to lamivudine therapy: is there more than meets the eye? Gut 2005; 54: Locarnini S, Mason WS. Cellular and virological mechanisms of HBV drug resistance. J Hepatol 2006; 44: Peters MG, Hann HH, Martin P, et al. Adefovir dipivoxil alone or in combination with lamivudine in patients with lamivudine-resistant chronic hepatitis B. Gastroenterology 2004; 126:

7 130. Chang TT, Gish RG, Hadziyannis SJ, et al. A dose-ranging study of the effi cacy and tolerability of entecavir in lamivudine-refractory chronic hepatitis B patients. Gastroenterology 2005; 129: Lau DT, Khokhar MF, Doo E, et al. Long-term therapy of chronic hepatitis B with lamivudine. Hepatology 2000; 32: Hadziyannis SJ, Papatheodoridis GV. Adefovir dipivoxil in the treatment of chronic hepatitis B virus infection. Expert Rev Anti-infect Ther 2004; 2: Sherman M, Yurdaydin C, Sollano J, et al. Entecavir for treatment of lamivudinerefractory, HBeAg-positive chronic hepatitis B. Gastroenterology 2006; 130: Sherman M, Martin P, Lee WM, et al. Entecavir results in continued virologic and biochemical improvement and HBeAg seroconversion through 96 weeks of treatment in lamivudine-refractory, HBeAg(+) chronic hepatitis B patients (ETV-026). Gastroenterology 2006; 130 (suppl 2): A765 (abstr) Xiong X, Flores C, Yang H, Toole JJ, Gibbs CS. Mutations in hepatitis B DNA polymerase associated with resistance to lamivudine do not confer resistance to adefovir in vitro. Hepatology ; 28: Schiff ER, Lai CL, Hadziyannis S, et al. Adefovir dipivoxil therapy for lamivudine-resistant hepatitis B in pre- and post-liver transplantation patients. Hepatology 2003; 38: Vassiliadis T, Nikolaidis N, Giouleme O, et al. Adefovir dipivoxil added to ongoing lamivudine therapy in patients with lamivudine-resistant hepatitis B e antigen-negative chronic hepatitis B. Aliment Pharmacol Ther 2005; 21: Lampertico P, Vigano P, Manenti E, Iavarone M, Lunghi G, Colombo M. Adefovir rapidly suppresses hepatitis B in HBeAg-negative patients developing genotypic resistance to lamivudine. Hepatology 2005; 42: Liaw YF, Lee CM, Chien RN, Yeh CT. Switching to adefovir monotherapy after emergence of lamivudine-resistant mutations in patients with liver cirrhosis. J Viral Hepat 2006; 13: Rapti I, Dimou E, Mitsoula P, Hadziyannis SJ. Adding-on versus switching-to adefovir tehrapy in lamivudine resistant HBeAg-negative chronic hepatitis B. Hepatology 2007; 45: Shaw T, Bowden S, Locarnini S. Rescue therapy for drug resistant hepatitis B: another argument for combination chemotherapy? Gastroenterology 2004; 126: Lampertico P, Vigano P, Manenti E, Iavarone M, Lunghi G, Colombo M. Five years of sequential LAM to LAM+ADV therapy suppresses HBV replication in most HBeAg-negative cirrhotics, preventing decompensation but not hepatocellular carcinoma. Hepatology 2005; 42 (suppl 1): 582A 83A (abstr) Villeneuve JP, Durantel D, Durantel S, et al. Selection of a hepatitis B virus strain resistant ot adefovir in a liver transplantation patient. J Hepatol 2003; 39: Locarnini S, Qi X, Arterburn S, et al. Incidence and predictors of emergence of adefovir resistant HBV during four years of adefovir dipivoxil (ADV) therapy for patients with chronic hepatitis B (CHB). J Hepatol 2005; 42 (suppl 2): 17 (abstr) Brunelle MN, Jacquard AC, Pichoud C, et al. Susceptibility to antivirals of a human HBV strain with mutations conferring resistance to both lamivudine and adefovir. Hepatology 2005; 41: Schildgen O, Sirma H, Funk A, et al. Variant of hepatitis B virus with primary resistance to adefovir. N Engl J Med 2006; 354: Kim DY, Lee JH, Lee DH, et al. Occurrence of primary adefovir resistance mutation in hepatitis B patients with YMDD mutation and lamivudine resistance. Gastroenterology 2006; 130 (suppl 2):A846 (abstr) Bartholomeusz A, Locarnini SA. Antiviral drug resistance: clinical consequences and molecular aspects. Semin Liver Dis 2006; 26: Gane E, Lai C-L, Min A, et al. Adefovir salvage therapy for virologic breakthrough in telbivudine-treated patients from the GLOBE study. J Hepatol 2007; 46 (suppl 1): S (abstr).

8 150. Vinayek R, Shakil O. Adverse events associated with interferon-alfa therapy in patients with chronic viral hepatitis. Viral Hep Rev 1997;3: Buti M, Esteban R. Drugs in development for hepatitis B. Drugs 2005; 65: Kanwal F, Gralnek IM, Martin P, Dulai GS, Farid M, Spiegel BM. Treatment alternatives for chronic hepatitis B virus infection: a cost-eff ectiveness analysis. Ann Intern Med 2005; 142: Buti M, Casado MA, Calleja JL, et al. Cost-eff ectiveness analysis of lamivudine and adefovir dipivoxil in the treatment of patients with HBeAg-negative chronic hepatitis B. Aliment Pharmacol Ther 2006;23: Dusheiko G, Mutimer D, Dakin H, Hughes N. Cost-eff ective strategies in the treatment of chronic hepatitis B with adefovir dipivoxil (ADV). Hepatology 2005; 42 (suppl 1): 586A (abstr).