• 1
    Lok ASF, McMahon BJ. AASLD practice guideline: chronic hepatitis B. HEPATOLOGY 2007; 45: 507539.
  • 2
    Keeffe EB, Dieterich DT, Han SH, Jacobson IM, Martin P, Schiff ER, 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: 936962.
  • 3
    Betteridge D. What is oxidative stress? Metabolism 2000; 49: 38.
  • 4
    Graziewicz MA, Day BJ, Copeland WC. The mitochondrial DNA polymerase as a target of oxidative damage. Nucleic Acids Res 2002; 30: 28172824.
  • 5
    Shlay JC, Visnegarawal F, Bartsch G, Wang J, Peng G, El-Sadr WM, et al. Body composition and metabolic changes in antiretroviral-naive patients randomized to didanosine and stavudine vs abacavir and lamivudine. J Acquir Immune Defic Syndr 2005; 38: 147155.
  • 6
    McKenzie R, Fried MW, Sallie R, Conjeevaram H, Di Bisceglie AM, Park Y, et al. Hepatic failure and lactic acidosis due to fialuridine (FIAU), an investigational nucleoside analog for chronic hepatitis B. N Engl J Med 1995; 333: 10991105.
  • 7
    Lewis W, Levine ES, Griniuviene B, Tankersley KO, Colacino JM, Sommadussi JP, et al. Fialuridine and its metabolites inhibit DNA polymerase gamma at sites of multiple adjacent analog incorporation, decrease mtDNA abundacne, and cause mitochondrial structural defects in cultured hepatoblasts. Proc Natl Acad Sci U S A 1996; 93: 35923597.
  • 8
    Medina DJ, Tsai CH, Hsiung GD, Cheng YC. Comparison of mitochondrial morphology, mitochondrial DNA content, and cell viability in cultured cells treated with three anti-human immunodeficiency virus dideoxynucleosides. Antimicrob Agents Chemother 1994; 38: 18241828.
  • 9
    Martin JL, Brown CE, Matthews-Davis N, Reardon JE. Effects of antiviral nucleoside on human DNA polymerases and mitochondrial DNA synthesis. Antimicrob Agents Chemother 1994; 38: 27432749.
  • 10
    McMomsey G, Lonergan JT. Mitochondrial dysfunction: patient monitoring and toxicity management. J Acquir Immune Defic Syndr 2004; 37: S30S35.
  • 11
    Venhoff N, Setzer B, Melkaoui K, Walker UA. Mitochondrial toxicity of tenofovir, emtricitabine, and abacavir alone and in combination with additional nucleoside reverse transcriptase inhibitors. Antivir Ther 2007; 12: 10751085.
  • 12
    Mazzucco CE, Hamatake RK, Colonno RJ, Tenney DJ. Entecavir for treatment of hepatitis B virus displays no in vitro mitochondrial toxicity or DNA polymerase gamma inhibition. Antimicrob Agents Chemother 2008; 52: 598605.
  • 13
    Walker UA, Setzer B, Venhoff N. Increased long-term mitochondrial toxicity in combination of nucleoside analog reverse-transcriptase inhibitors. AIDS 2002; 16: 21652173.
  • 14
    Hulgan T, Haas DW, Haines JL, Ritchie MD, Robbins GK, Shafer RW, et al. Mitochondrial haplogroups and peripheral neuropathy during antiretroviral therapy: an adult AIDS clinical trials group study. AIDS 2005; 19: 13411349.
  • 15
    Van Rompay KKA, Durand-Gasselin L, Brignolo LL, Ray AS, Abel K, Cihlar T, et al. Chronic administration of tenofovir to rhesus macaques from infancy through adulthood and pregnancy: summary of pharmacokinetics and biological and virological effects. Antimicrob Agents Chemother 2008; 52: 31443160.
  • 16
    Fisher EJ, Chaloner K, Cohn DL, Grant LB, Alston B, Brosgart CL, et al. Community programs for clinical research on AIDS: the safety and efficacy of adefovir dipivoxil in patients with adefovir dipivoxil and HIV disease: a randomized, placebo controlled trial. AIDS 2001; 15: 16951700.
  • 17
    Kahn J, Lagakos S, Wulfsohn M, Cherng D, Miller M, Cherrington J, et al. Efficacy and safety of adefovir dipivoxil with antiretroviral therapy: a randomized controlled trial. JAMA 1999; 282: 23052312.
  • 18
    Izzedine H, Hulot JS, Launay-Vacher V, Marcellini P, Hadziyannis SJ, Currie G, et al. Adefovir Dipivoxil International 437 Study Group, renal safety of adefovir dipivoxil in patients with chronic hepatitis B: two double-blind, randomized, placebo controlled studies. Kidney Int 2004; 66: 11531158.
  • 19
    Verheist D, Monge M, Meynard JL, Fouqueray B, Mougenot B, Girard PM, et al. Fanconi syndrome and renal failure induced by tenofovir: a first case report. Am J Kidney Dis 2002; 40: 13311333.
  • 20
    Izzedine H, Isnard-bagnis C, Hulot JS, Vittecoq D, Cheng A, Jais CK, et al. Renal safety of tenofovir in HIV treatment-experienced patients. AIDS 2004; 18: 10741076.
  • 21
    Karras A, Lafaurie M, Furco A, Bourgarit A, Droz D, Sereni D, et al. Tenofovir-related nephrotoxicity in human immunodeficiency virus-infected patients: three cases of renal failure, fanconi syndrome, and nephrogenic diabetes insipidus. Clin Infect Dis 2003; 36: 10701073.
  • 22
    Lee JC, Marosok RD. Acute tubular necrosis in a patient receiving tenofovir. AIDS 2003; 17: 35432544.
  • 23
    Coca S, Parzella MA. Acute renal failure associated with tenofovir: evidence of drug-induced nephrotoxicity. Am J Med Sci 2002; 324: 342344.
  • 24
    Izzedine H, Launay-Vacher V, Deray G. Antiviral drug-induced nephrotoxicity. Am J Kidney Dis 2005; 45: 804817.
  • 25
    Jonas MM, Little NR, Gardner SD. Long-term lamivudine treatment of children with chronic hepatitis B: durability of therapeutic responses and safety. J Viral Hepat 2008; 15: 2027.
  • 26
    Sokal EM, Kelly DA, Mizerski J, Badia IB, Areias JA, Schwarz KB, et al. Long-term lamivudine therapy for children with HBeAg positive chronic hepatitis B. HEPATOLOGY 2006; 43: 225232.
  • 27
    Lai CL, Chien RN, Leung NW, Chang TT, Guan R, Tai DI, et al. A one-year trial of lamivudine for chronic hepatitis B. N Engl J Med 1998; 339: 6168.
  • 28
    Liaw YF, Sung JJ, Chow WC, Farrell G, Lee CZ, Yuen H, et al. Lamivudine for patients with chronic hepatitis B and advanced liver disease. N Engl J Med 2004; 351: 15211531.
  • 29
    Lok AS, Lai CL, Leung N, Yao GB, Cui ZY, Schiff ER, et al. Long-term safety of lamivudine treatment in patients with chronic hepatitis B. Gastroenterology 2003; 125: 17141722.
  • 30
    Adani GL, Baccarani U, Risaliti A, Bresadola F, Della Rocca G, Viale P. Rhabdomyolysis due to lamivudine administration in a liver transplant recipient. Am J Transplant 2005; 5: 634.
  • 31
    Fodale V, Mazzeo A, Pratico C, Aguennouz M, Toscano A, Santamaria LB, et al. Fatal exacerbation of peripheral neuropathy during lamivudine therapy: evidence for iatrogenic mitochondrial damage. Anaesthesia 2005; 60: 806810.
  • 32
    Bayraekci US, Baskin E, Ozcay F, Ozdemir BH, Karakayali H, Habernal M, et al. Renal fanconi syndrome and myopathy after liver transplantation: drug related mitochondrial cytopathy? Pediatr Transplant 2008; 12: 109112.
  • 33
    Cupler EJ, Dalakas MC. Exacerbation of peripheral neuropathy by lamivudine. Lancet 1995; 345: 460461.
  • 34
    Ojetti VA, Gasharrini A, Migneco A, Fiore A, Santoliquido D, DeMartini S, et al. Lamivudine induced muscle mitochondrial toxicity. Dig Liver Dis 2002; 34: 384385.
  • 35
    Khawcharoenporn T, Shikuma CM, Williams AE, Chow DC. Lamivudine associated macrocytosis in HIV-infected patients. Int J STD AIDS 2007; 18: 3940.
  • 36
    Fontana RJ. Management of patients with decompensated HBV cirrhosis. Semin Liver Dis 2003; 23: 89100.
  • 37
    Lau GK, Yiu HH, Fong DY, Cheng HC, Au WY, Lai LS. Early is superior to deferred preemptive lamivudine therapy for hepatitis B patients undergoing chemotherapy. Gastroenterology 2003; 125: 17421749.
  • 38
    Marcellin P, Change TT, Lim SG, Tong MJ, Sievert W, Shiffman ML, et al. Adefovir dipivoxil for the treatment of hepatitis e antigen positive chronic Hepatitis B. N Engl J Med 2003; 348: 808817.
  • 39
    Hadziyannis SJ, Tassopoulos NC, Heathcote EJ, Chang TT, Kitis G, Rizzetto M, et al. Adefovir dipivoxil for the treatment of hepatitis B e antigen negative chronic hepatitis B. N Engl J Med 2003; 348: 800808.
  • 40
    Hadziyannis SJ, Tassopoulos NC, Heathcote EJ, Chang TT, Kitis G, Rizzetto M, et al. Long-term therapy with adefovir dipivoxil for HBeAg-negative chronic hepatitis B for up to 5 years. Gastroenterology 2006; 131: 17431751.
  • 41
    Marcellin P, Chang TT, Lim SGL, Sievert W, Tong M, Arterburn S, et al. Long-term efficacy and safety of adefovir dipivoxil for the treatment of hepatitis B e antigen positive chronic hepatitis B. HEPATOLOGY 2008; 48: 750758.
  • 42
    Schiff E, Lai CL, Hadziyannis S, Neuhaus P, Terrault N, Colombo M, et al. Adefovir dipivoxil for wait-listed and post-liver transplantation patients with lamivudine-resistant hepatitis B: final long-term results. Liver Transpl 2007; 13: 349360.
  • 43
    Tanji N, Tanji K, Kambham N, Markowitz GS, Bell A, D'agati VD. Adefovir nephrotoxicity: Possible role of mitochondiral DNA depletion. Hum Pathol 2001; 32: 734740.
  • 44
    Imaoka T, Kusuhara H, Adachi M, Schuetz JD, Takeuchi K, Sugiyama Y. Functional involvement of multidrug resistance-associated protein 4 in the renal elimination of the antiviral drugs adefovir and tenofovir. Mol Pharmacol 2007; 71: 619627.
  • 45
    Fontaine H, Vallet-Pichard A, Chaix ML, Currie G, Serpaggi J, Verkarre V, et al. Efficacy and safety of adefovir dipivoxil in kidney recipients, hemodialysis patients, and patients with renal insufficiency. Transplantation 2005; 80: 10861092.
  • 46
    Lampertico P, Vigano M, Manenti E, Iavarone M, Sablon E, Colombo M, et al. Low resistance to adefovir combined with lamivudine: a 3-year study of 145 lamivudine resistant hepatitis B patients. Gastroenterology 2007; 133: 14451451.
  • 47
    Sung JJ, Lai JY, Zeuzem S, Chow WC, Heathcote EJ, Perrillo RP, et al. Lamivudine compared with lamivudine and adefovir for the treatment of HBeAg positive chronic hepatitis B. J Hepatol 2008; 48: 728735.
  • 48
    Vigano M, Lampertico P, Iavarone M, Tontini GE, Facchetti F, Colombo M. High risk of renal impairment and arterial hypertension during long-term adefovir and lamivudine combination therapy in patients with lamivudine-resistant chronic hepatitis B [Abstract]. HEPATOLOGY 2008; 48(4 Suppl 1 ): 7081.
  • 49
    Hui CK, Zhang HY, Bowden S, Locarnini JM, Leung KW, Yueng YH, et al. 96 weeks combination of adefovir dipivoxil plus emtricitabine vs adefovir dipivoxil monotherpay in the treatment of chronic hepatitis B. J Hepatol 2008; 48: 714720.
  • 50
    Wursthorn K, Lutgehetmann M, Dandri M, Volz T, Buggisch P, Zollner B, et al. Peginterferon alpha-2b plus adefovir induce strong cccDNA decline and HBsAg reduction in patients with chronic hepatitis B. HEPATOLOGY 2006; 44: 675684.
  • 51
    Lai CL, Shouval D, Lok ASF, Goodman Z, Chang TT, Cheinquer H, et al. Entecavir verus lamivudine for patients with HBeAg-negative chronic hepatitis B. N Engl J Med 2006; 354: 10111020.
  • 52
    Chang TT, Gish RG, de Man R, Gadano A, Sollano J, Chao YC, et al. A comparison of entecavir and lamivudine for HBeAg-positive chronic hepatitis B. N Engl J Med 2006; 354: 10011010.
  • 53
    Gish RG, Lok ASF, Chang TT, de Man R, Gadano A, Sollano J, et al. Entecavir therapy for up to 96 weeks in patients with HBeAg-positive chronic hepatitis B. Gastroenterology 2007; 133: 14371444.
  • 54
    Han SH, Chang TT, Chao YC, Yoon SK, Gish RG, Cheinquer H, et al. Five years of continuous entecavir for nucleoside-naïve HBeAg (+) chronic hepatitis B: results from study ETV 901 [Abstract]. HEPATOLOGY 2008; 48(4 Suppl 1 ): 705A.
  • 55
    Sherman M, Yurdaydin C, Sollano J, Silva M, Liaw Y, Cianciara J, et al. Entecavir for treatment of lamivudine-refractory HBeAg + chronic hepatitis B. Gastroenterology 2006; 130: 20392049.
  • 56
    Colonno RJ, Rose RE, Pokornowski K, Baldick CJ, Eggers B, Xu D, et al. Four-year assessment of ETV resistance in nucleoside-naive and lamivudine refractory patients [Abstract]. J Hepatol 2007; 46(Suppl 1): S294.
  • 57
    Schollmeyer J, Lutghetmann M, Volz T, Lohse AW, Buggisch P, Meyer TH, et al. Combination of entecavir and tenofovir as a rescue therapy is safe and highly efficient in cirrhotic HBV mono-infected patients with the history of multiple prior treatment failures [Abstract]. HEPATOLOGY 2008; 48(Suppl 1): A985.
  • 58
    Kamar N, Milioto O, Alric L, Kahwaji LE, Cointault O, Lavayssieree L, et al. Entecavir therapy for adefovir-resistant hepatitis B virus infection in kidney and liver allograft recipients. Transplantation 2008; 86: 611614.
  • 59
    Lin PF, Nowicka B, Terry B, Zhang S, Wang C, Fan L, et al. Entecavir exhibits inhibitory activity against human immunodeficiency virus under conditions of reduced viral challenge. Antimicrob Agents Chemother 2008; 52: 17591767.
  • 60
    Lai CL, Gane E, Liaw YF, Hsu CW, Thongsawat S, Wang Y, et al. Telbivudine versus lamivudine in patients with chronic hepatitis B. N Engl J Med 2007; 357: 25762588.
  • 61
    Liaw YF, Gane E, Leung N, Zeuzem S, Wang Y, Lai CL et al. 2-year GLOBE Trial results: telbivudine is superior to lamivudine in patients with chronic hepatitis B. Gastroenterology 2009; 136: 486495.
  • 62
    United States Food and Drug Administration. Potential Signals of Serious Risks/New Safety Information Identified from the Adverse Event Reporting System (AERS) between January-March 2008. Accessed February 2009.
  • 63
    Lai CL, Leung N, Teo EK, Tong M, Wong F, Hann HW, 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: 528536.
  • 64
    Marcellin P, Jacobson I, Habersetzer F, Senturk H, Andreone P, Moyes C, et al. Tenofovir disoproxil fumarate (TDF) for the treatment of HBeAg-negative chronic hepatitis B: week 72 TDF data and week 24 adefovir dipivoxil switch data. J Hepatol 2008; 48(Suppl 2): S26.
  • 65
    Sheldon J, Camino N, Rodes B, Bartholomeusz A, Kuiper M, Tacke F, et al. Selection of hepatitis B virus polymerase mutations in HIV-coinfected patients treated with tenofovir. Antivir Ther 2005; 10: 727734.
  • 66
    van Bommel F, Wunsche T, Mauss S, Reinke P, Bergk A, Schurmann D, et al. Comparison of adefovir and tenofovir in the treatment of lamivudine-resistant hepatitis B virus infection. HEPATOLOGY 2004; 40: 14211425.
  • 67
    van Bommel F, de Man RA, Erhardt A, Huppe D, Stein K, Buggisch P, et al. First multicenter evaluation of tenofovir in nucleos(t)ide analog experienced patients with HBV monoinfection [Abstract]. HEPATOLOGY 2007; 46(Suppl 1): 664A.
  • 68
    Tan J, Degertekin B, Wong SN, Husain M, Oberhelman K, Lok AS. Tenofovir monotherapy is effective in hepatitis B patients with antiviral treatment failure to adefovir in the absence of adefovir-resistant mutations. J Hepatol 2008; 48: 391398.
  • 69
    Izzedine H, Hulot JS, Vittecoq D, Gallent JE, Staszewski S, Launey-Vacher V, et al. Long-term renal safety profile of tenofovir disproxil fumarate in antiretroviral naive, HIV-1 infected patients: data derived from a double-blind randomized active controlled multicenter study. Nephrol Dial Transplant 2005; 20: 743746.
  • 70
    Gallant JE, Dejesus E, Arribas JR, Pozniak AL, Gazzard B, Campo RE, et al. Tenofovir DF, emtricitabine, and efavirenz vs zidovudine, lamivudine, and efavirenz. N Engl J Med 2006; 354: 251260.
  • 71
    Winston J, Shepp DH. Estimating renal function in patients on tenofovir disproxil fumarate: suggestions for safer use. HIV Med 2006; 7: 484485.
  • 72
    Parsonage MJ, Wilkins EG, Snowden N, Issa BG, Savage MW. The development of hypophosphataemic osteomalaica with myopathy in two patients with HIV infection receiving tenofovir therapy. HIV Med 2005; 6: 341346.
  • 73
    Cassetti LJ, Madruga JV, Suleiman JM, Etzel A, Zhong L, Cheng AK, et al. The safety and efficacy of tenofovir DF in combination with lamivudine and efavirenz through 6 years in antiretroviral-naïve, HIV-1 infected patients. HIV Clin Trials 2007; 8: 164172.
  • 74
    Gallant J, Staszewski ES, Pozniak AL, DeJesus E, Suleiman JM, Miller MD, et al. Efficacy and safety of tenofovir DF vs stavudine in combination therapy in anti-retroviral naïve patients: a 3-year randomized trial. JAMA 2004; 292: 191201.
  • 75
    Gafni RL, Hazra R, Reynolds JC, Maldarelli F, Tuillo AN, DeCarlo E, et al. Tenofovir disoproxil fumarate and an optimized background regimen of antiretroviral agents as salvage therapy: impact on bone mineral density in HIV-infected children. Pediatrics 2006; 118: e711e718.
  • 76
    Gupta SK, Eustace JA, Winston JA, Boydstun II, Ahuja TS, Rodriguez RA, et al. Guidelines for the management of chronic kidney disease in HIV-infected patients. Recommendations of the HIV Medicine Association of The Infectious Diseases Society of America. Clin Infect Dis 2005; 40: 15591585.
  • 77
    Neff GW, O'Brien CB, Nery J, Shire N, Montalbano M, Ruiz P, et al. Outcomes in liver transplant recipients with hepatitis B virus: resistance and recurrence patterns from a large transplant center over the last decade. Liver Transpl 2004; 10: 13721378.
  • 78
    Benhamou Y, Fleury H, Trimoulet P, Pellegrin I, Urbinelli R, Katlama C, et al. Anti-hepatitis B virus efficacy of tenofovir disoproxil fumarate in HIV-infected patients. HEPATOLOGY 2006; 43: 548555.
  • 79
    Peters MG, Andersen J, Lynch P, Liu T, Alston-Smith B, Brosgart CL, et al. Randomized controlled study of tenofovir and adefovir in chronic hepatitis B virus and HIV infection: ACTG A5127. HEPATOLOGY 2006; 44: 11101116.
  • 80
    Terrault NA, Jacobson IM. Treating chronic hepatitis B infection in patients who are pregnant or are undergoing immunosuppressive chemotherapy. Semin Liver Dis 2007; 27: 1824.
  • 81
    Xiao XM, Li AZ, Chen X, Zhu K, Miao J. Prevention of vertical hepatitis B transmission by hepatitis B immunoglobulin in the third trimester of pregnancy. Int J Gynaecol Obstet 2007; 96: 167170.
  • 82
    Ngui SL, Andrews NJ, Underhill GS, Heptonstall J, Teo CG. Failed postnatal immunoprophylaxis for hepatitis B. Characteristics of maternal hepatitis B virus as risk factors. Clin Infect Dis 1998; 27: 100106.
  • 83
    van Zonneveld M, van Nunen AB, Niesters HGM, de Man RA, Schalm SW, Janssen HL. Lamivudine treatment during pregnancy to prevent perinatal transmission of hepatitis B virus infection. J Viral Hepat 2003; 10: 294297.
  • 84
    Su GG, Pan KH, Zhao NF, Fang SH, Yang DH, Zhou Y. Efficacy and safety of lamivudine treatment for chronic hepatitis B in pregnancy. World J Gastroenterol 2004; 10: 910912.
  • 85
    Xu WM, Cui YT, Wang L, Yang H, Liang ZQ, Li XM, et al. Lamivudine in late pregnancy to prevent perinatal transmission of hepatitis B virus infection: a multicentre, randomized, double-blind, placebo-controlled study. J Viral Hepat 2009; 16: 94103.
  • 86
    The Antiretroviral Pregnancy Registry. Available at: Accessed February, 2009.
  • 87
    Watts DH, Covington DL, Beckerman K. Assessing the risk of birth defects associated with antiretroviral exposure during pregnancy. Am J Obstet Gynecol 2004; 191: 985992.
  • 88
    Dybul M, Fauci AS, Bartlett JG, Kaplan JE, Pau AK. Guidelines for using antiretroviral agents among HIV-infected adults and adolescents. Recommendations on the Panel on Clinical Practices for the Treatment of HIV. MMWR Recomm Rep 2002; 51: 155.
  • 89
    Mandelbrot L, Kermarrec N, Marcollet A, Lafanechere A, Longuet P, Chosidow D, et al. Case report: nucleoside analog induced lactic acidosis in the third trimester of pregnancy. AIDS 2003; 17: 272273.
  • 90
    Blance S, Tardieu M, Benhammou V, Warszawski J, Rustin P. Mitochondrial dysfunction following perinatal exposure to nucleoside analogs. AIDS 2006; 20: 16851690.
  • 91
    Brogly SB, Ylitalo N, Mofenson LM, Oleske J, Van Dyke R, Crain MJ, et al. In utero nucleoside reverse transcriptase inhibitor exposure and signs of possible mitochondrial dysfunction in HIV-uninfected children. AIDS 2007; 21: 929938.