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Semin Liver Dis 2003; 23(2): 125-136
DOI: 10.1055/s-2003-39951
Copyright © 2002 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA. Tel.: +1(212) 584-4662

Hepatitis B in the Human Immunodeficiency Virus-Infected Patient: Epidemiology, Natural History, and Treatment

Chloe L. Thio
  • Assistant Professor of Medicine, Johns Hopkins University, Baltimore, Maryland
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Publikationsverlauf

Publikationsdatum:
11. Juni 2003 (online)

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ABSTRACT

Coinfection with hepatitis B virus (HBV) is common in the human immunodeficiency virus-1 (HIV)-infected patient because of shared modes of transmission. HBV does not appear to alter HIV disease progression; however, HBV infection is more frequent and more severe in the HIV-infected population, emphasizing the importance of preventing HBV infection. The goal of anti-HBV therapy is prevention of cirrhosis because therapy does not eradicate the hepatic reservoirs (cccDNA). The approved therapies-interferon-alfa, lamivudine, and adefovir-each have a niche in the treatment of chronic hepatitis B in the HIV-infected population, but none has been well-studied in this setting. As new drugs currently in clinical trials become available, therapy for chronic hepatitis B will enter the promising era of combination therapy.

KEYWORDS

HIV - hepatitis B - interferon-alfa - lamivudine - adefovir

REFERENCES

  • 1 Mahoney F J. Update on diagnosis, management, and prevention of hepatitis B virus infection.  Clin Microbiol Rev . 1999;  12 351-366
    PubMedGoogle Scholar
  • 2 Homann C, Krogsgaard K, Pedersen C, Andersson P, Nielsen J O. High incidence of hepatitis B infection and evolution of chronic hepatitis B infection in patients with advanced HIV infection.  J Acquir Immune Defic Syndr . 1991;  4 416-420
    PubMedGoogle Scholar
  • 3 Rustgi V K, Hoofnagle J H, Gerin J L. et al . Hepatitis B virus infection in the acquired immunodeficiency syndrome.  Ann Intern Med . 1984;  101 795-797
    PubMedGoogle Scholar
  • 4 Centers for Disease Control and Prevention. 1999 USPHS/ IDSA guidelines for the prevention of opportunistic infections in persons infected with human immunodeficiency virus: disease-specific recommendations. USPHS/IDSA Prevention of Opportunistic Infections Working Group. US Public Health Services/Infectious Diseases Society of America.  MMWR Morb Mortal Wkly Rept . 1999;  48 1-82
    PubMedGoogle Scholar
  • 5 MacKellar D A, Valleroy L A, Secura G M. et al . Two decades after vaccine license: hepatitis B immunization and infection among young men who have sex with men.  Am J Public Health . 2001;  91 965-971
    PubMedGoogle Scholar
  • 6 Kao J H. Hepatitis B viral genotypes: clinical relevance and molecular characteristics.  J Gastroenterol Hepatol . 2002;  17 643-650
    CrossrefPubMedGoogle Scholar
  • 7 Kao J H, Chen P J, Lai M Y, Chen D S. Hepatitis B genotypes correlate with clinical outcomes in patients with chronic hepatitis B.  Gastroenterology . 2000;  118 554-559
    CrossrefPubMedGoogle Scholar
  • 8 Hollinger F B. Hepatitis B virus. In: Knipe DM, Howley PM, et al, eds. Virology, 4th ed Philadelphia: Lippincott Williams and Wilkins 2001: 2971-3036
    Google Scholar
  • 9 Sakai T, Shiraki K, Inoue H. et al . HBV subtype as a marker of the clinical course of chronic HBV infection in Japanese patients.  J Med Virol . 2002;  68 175-181
    CrossrefPubMedGoogle Scholar
  • 10 Coleman P J, McQuillan G M, Moyer L A, Lambert S B, Margolis H S. 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;  178 954-959
    PubMedGoogle Scholar
  • 11 McQuillan G M, Coleman P J, 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;  89 14-18
    PubMedGoogle Scholar
  • 12 Kingsley L A, Rinaldo Jr R C, Lyter D W. et al . Sexual transmission efficiency of hepatitis B virus and human immunodeficiency virus among homosexual men.  JAMA . 1990;  264 230-234
    CrossrefPubMedGoogle Scholar
  • 13 Levine O S, Vlahov D, Koehler J. et al . Seroepidemiology of hepatitis B virus in a population of injecting drug users- association with drug injection patterns.  Am J Epidemiol . 1995;  142 331-341
    PubMedGoogle Scholar
  • 14 Centers for Disease Control and Prevention. Recommendations for protection against viral hepatitis.  MMWR Morb Mortal Wkly Rept . 1985;  34 313-335
    PubMedGoogle Scholar
  • 15 Rehermann B, Ferrari C, Pasquinelli C, Chisari F V. The hepatitis B virus persists for decades after patients' recovery from acute viral hepatitis despite active maintenance of a cytotoxic T-lymphocyte response.  Nat Med . 1996;  2 1104-1108
    CrossrefPubMedGoogle Scholar
  • 16 McMahon B J, Holck P, Bulkow L, Snowball M. Serologic and clinical outcomes of 1536 Alaska natives chronically infected with hepatitis B virus.  Ann Intern Med . 2001;  135 759-768
    CrossrefPubMedGoogle Scholar
  • 17 Liaw Y F, Tai D I, Chu C M, Chen T J. The development of cirrhosis in patients with chronic type B hepatitis: a prospective study.  Hepatology . 1988;  8 493-496
    PubMedGoogle Scholar
  • 18 Fattovich G, Brollo L, Giustina G. et al . Natural history and prognostic factors for chronic hepatitis type B.  Gut . 1991;  32 294-298
    PubMedGoogle Scholar
  • 19 Yang H I, Lu S N, Liaw Y F. et al . Hepatitis B e antigen and the risk of hepatocellular carcinoma.  N Engl J Med . 2002;  347 168-174
    PubMedGoogle Scholar
  • 20 Beasley R P, Hwang L Y, Lin C C, Chien C S. Hepatocellular carcinoma and hepatitis B virus: a prospective study of 22707 men in Taiwan.  Lancet . 1981;  2 1129-1133
    PubMedGoogle Scholar
  • 21 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;  6 167-172
    PubMedGoogle Scholar
  • 22 de Jongh E F, Janssen H L, De Man A R. Survival and prognostic indicators in hepatitis B surface antigen-positive cirrhosis of the liver.  Gastroenterology . 1992;  103 1630-1635
    PubMedGoogle Scholar
  • 23 Davis G L, Hoofnagle J H, Waggoner J G. Spontaneous reactivation of chronic hepatitis B virus infection.  Gastroenterology . 1984;  86 230-235
    PubMedGoogle Scholar
  • 24 Torbenson M, Thomas D L. Occult hepatitis B.  Lancet Infect Dis . 2002;  2 479-486
    CrossrefPubMedGoogle Scholar
  • 25 2001 USPHS/IDSA guidelines for the prevention of opportunistic infections in persons infected with human immunodeficiency virus. HIV Clin Trials .  2001;  2 493-554
    Google Scholar
  • 26 Hofer M, Joller-Jemelka H I, Grob P J, Luthy R, Opravil M. Frequent chronic hepatitis B virus infection in HIV-infected patients positive for antibody to hepatitis B core antigen only. Swiss HIV Cohort Study.  Eur J Clin Microbiol Infect Dis . 1998;  17 6-13
    CrossrefPubMedGoogle Scholar
  • 27 Silva A E, McMahon B J, Parkinson A J. et al . Hepatitis B virus DNA in persons with isolated antibody to hepatitis B core antigen who subsequently received hepatitis B vaccine.  Clin Infect Dis . 1998;  26 895-897
    PubMedGoogle Scholar
  • 28 Lok A S, McMahon B J. Chronic hepatitis B.  Hepatology . 2001;  34 1225-1241
    CrossrefPubMedGoogle Scholar
  • 29 Thio C L, Seaberg E C, Skolasky R L. et al . HIV-1, hepatitis B virus, and risk of liver-related mortality in the Multicenter AIDS Cohort Study (MACS).  Lancet . 2002;  360 1921-1926
    CrossrefPubMedGoogle Scholar
  • 30 Colin J F, Cazals-Hatem D, Loriot M A. et al . Influence of human immunodeficiency virus infection on chronic hepatitis B in homosexual men.  Hepatology . 1999;  29 1306-1310
    CrossrefPubMedGoogle Scholar
  • 31 Gilson R JC, Hawkins A E, Beecham M R. et al . Interactions between HIV and hepatitis B virus in homosexual men: effects on the natural history of infection.  AIDS . 1997;  11 597-606
    CrossrefPubMedGoogle Scholar
  • 32 Bodsworth N J, Cooper D A, Donovan B. The influence of human immunodeficiency virus type 1 infection on the development of the hepatitis B carrier state.  J Infect Dis . 1991;  163 1138-1140
    PubMedGoogle Scholar
  • 33 Vento S, Di Perri G, Garofano T, Concia E, Bassetti D. Reactivation of hepatitis B in AIDS.  Lancet . 1989;  2 108-109
    PubMedGoogle Scholar
  • 34 Lazizi Y, Grangeot-Keros L, Delfraissy J F. et al . Reappearance of hepatitis B virus in immune patients infected with the human immunodeficiency virus type 1.  J Infect Dis . 1988;  158 666-667
    PubMedGoogle Scholar
  • 35 Biggar R J, Goedert J J, Hoofnagle J. Accelerated loss of antibody to hepatitis B surface antigen among immunodificient homosexual men infected with HIV.  N Engl J Med . 1987;  316 630
    CrossrefPubMedGoogle Scholar
  • 36 Davies S E, Portmann B C, O'Grady J G. et al . Hepatic histological findings after transplantation for chronic hepatitis B virus infection, including a unique pattern of fibrosing cholestatic hepatitis.  Hepatology . 1991;  13 150-157
    CrossrefPubMedGoogle Scholar
  • 37 Fang J W, Wright T L, Lau J Y. Fibrosing cholestatic hepatitis in patient with HIV and hepatitis B.  Lancet . 1993;  342 1175
    PubMedGoogle Scholar
  • 38 Scharschmidt B F, Held M J, Hollander H H. et al . Hepatitis B in patients with HIV infection: relationship to AIDS and patient survival.  Ann Intern Med . 1992;  117 837-838
    CrossrefPubMedGoogle Scholar
  • 39 Solomon R E, Van Raden M, Kaslow R A. et al . Association of hepatitis B surface antigen and core antibody with acquisition and manifestations of human immunodeficiency virus type 1 HIV-1) infection.  Am J Public Health . 1990;  80 1475-1478
    PubMedGoogle Scholar
  • 40 Eskild A, Magnus P, Petersen G. et al . Hepatitis B antibodies in HIV-infected homosexual men are associated with more rapid progression to AIDS.  AIDS . 1992;  6 571-574
    PubMedGoogle Scholar
  • 41 Ockenga J, Tillmann H L, Trautwein C. et al . Hepatitis B and C in HIV-infected patients. Prevalence and prognostic value.  J Hepatol . 1997;  27 18-24
    CrossrefPubMedGoogle Scholar
  • 42 Saves M, Vandentorren S, Daucourt V. et al . Severe hepatic cytolysis: incidence and risk factors in patients treated by antiretroviral combinations. Aquitaine Cohort, France, 1996-1998. Groupe d'Epidemiologie Clinique de Sida en Aquitaine (GECSA).  AIDS . 1999;  13 F115-F121
    CrossrefPubMedGoogle Scholar
  • 43 Sulkowski M S, Thomas D L, Chaisson R E, Moore R D. Hepatotoxicity associated with antiretroviral therapy in adults infected with human immunodeficiency virus and the role of hepatitis C or B virus infection.  JAMA . 2000;  283 74-80
    CrossrefPubMedGoogle Scholar
  • 44 Carr A, Cooper D A. Restoration of immunity to chronic hepatitis B infection in HIV-infected patient on protease inhibitor.  Lancet . 1997;  349 995-996
    PubMedGoogle Scholar
  • 45 Velasco M, Moran A, Tellez M J. Resolution of chronic hepatitis B after ritonavir treatment in an HIV-infected patient (Letter).  N Engl J Med . 1999;  340 1765-1766
    CrossrefPubMedGoogle Scholar
  • 46 Altfeld M, Rockstroh J K, Addo M. et al . Reactivation of hepatitis B in a long-term anti-HBs-positive patient with AIDS following lamivudine withdrawal.  J Hepatol . 1998;  29 306-309
    CrossrefPubMedGoogle Scholar
  • 47 Bessesen M, Ives D, Condreay L, Lawrence S, Sherman K E. Chronic active hepatitis B exacerbations in human immunodeficiency virus-infected patients following development of resistance to or withdrawal of lamivudine.  Clin Infect Dis . 1999;  28 1032-1035
    CrossrefPubMedGoogle Scholar
  • 48 Manegold C, Hannoun C, Wywiol A. et al . Reactivation of hepatitis B virus replication accompanied by acute hepatitis in patients receiving highly active antiretroviral therapy.  Clin Infect Dis . 2001;  32 144-148
    CrossrefPubMedGoogle Scholar
  • 49 Centers for Disease Control and Prevention. Sexually transmitted diseases treatment guidelines 2002.  MMWR . 2002;  51 63-66
    PubMedGoogle Scholar
  • 50 Collier A C, Corey L, Murphy V L, Handsfield H H. Antibody to human immunodeficiency virus and suboptimal response to hepatitis B vaccination.  Ann Intern Med . 1988;  109 101-105
    PubMedGoogle Scholar
  • 51 Odaka N, Eldred L, Cohn S. et al . Comparative immunogenicity of plasma and recombinant hepatitis B virus vaccines in homosexual men.  JAMA . 1988;  260 3635-3637
    CrossrefPubMedGoogle Scholar
  • 52 Bruguera M, Cremades M, Salinas R. et al . Impaired response to recombinant hepatitis B vaccine in HIV-infected persons.  J Clin Gastroenterol . 1992;  14 27-30
    PubMedGoogle Scholar
  • 53 Keet I P, van Doornum G, Safary A, Coutinho R A. Insufficient response to hepatitis B vaccination in HIV-positive homosexual men.  AIDS . 1992;  6 509-510
    CrossrefPubMedGoogle Scholar
  • 54 Rey D, Krantz V, Partisani M. et al . Increasing the number of hepatitis B vaccine injections augments anti-HBs response rate in HIV-infected patients. Effects on HIV-1 viral load.  Vaccine . 2000;  18 1161-1165
    CrossrefPubMedGoogle Scholar
  • 55 Are booster immunisations needed for lifelong hepatitis B immunity? European Consensus Group on Hepatitis B Immunity.  Lancet . 2000;  355 561-565
    CrossrefPubMedGoogle Scholar
  • 56 Vento S, Garofano T, Renzini C. et al . Fulminant hepatitis associated with hepatitis A virus superinfection in patients with chronic hepatitis C.  N Engl J Med . 1998;  338 286-290
    CrossrefPubMedGoogle Scholar
  • 57 Okoshi S, Igarashi M, Suda T. et al . Remote development of hepatocellular carcinoma in patients with liver cirrhosis type B serologically cured for HBs antigenemia with long- standing normalization of ALT values.  Dig Dis Sci . 2002;  47 2002-2006
    CrossrefPubMedGoogle Scholar
  • 58 Higashi Y, Tada S, Miyase S. et al . Correlation of clinical characteristics with detection of hepatitis B virus X gene in liver tissue in HBsAg-negative, and HCV-negative hepatocellular carcinoma patients.  Liver . 2002;  22 374-379
    PubMedGoogle Scholar
  • 59 Lopez V A, Bourne E J, Lutz M W, Condreay L D. Assessment of the COBAS Amplicor HBV Monitor Test for quantitation of serum hepatitis B virus DNA levels.  J Clin Microbiol . 2002;  40 1972-1976
    CrossrefPubMedGoogle Scholar
  • 60 Brook M G, Karayiannis P, Thomas H C. Which patients with chronic hepatitis B virus infection will respond to alpha-interferon therapy?.  <~>A statistical analysis of predictive factors. Hepatology . 1989;  10 761-763
    PubMedGoogle Scholar
  • 61 Perrillo R P, Schiff E R, Davis G L. 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;  323 295-301
    PubMedGoogle Scholar
  • 62 Perrillo R, Tamburro C, Regenstein F. et al . Low-dose, titratable interferon alfa in decompensated liver disease caused by chronic infection with hepatitis B virus.  Gastroenterology . 1995;  109 908-916
    PubMedGoogle Scholar
  • 63 Wong D K, Cheung A M, O'Rourke K. et al . Effect of alfa-interferon treatment in patients with hepatitis B e antigen-positive chronic hepatitis B.  Ann Intern Med . 1993;  119 312-323
    PubMedGoogle Scholar
  • 64 Krogsgaard K. The long-term effect of treatment with interferon-alpha 2a in chronic hepatitis B. The Long-Term Follow-up Investigator Group. The European Study Group on Viral Hepatitis (EUROHEP). Executive Team on Anti-Viral Treatment.  J Viral Hepat . 1998;  5 389-397
    CrossrefPubMedGoogle Scholar
  • 65 Fattovich G, Giustina G, Realdi G. et al . Long-term outcome of hepatitis B e antigen-positive patients with compensated cirrhosis treated with interferon alfa.  Hepatology . 1997;  26 1338-1342
    CrossrefPubMedGoogle Scholar
  • 66 Wong D K, Yim C, Naylor C D. et al . Interferon alfa treatment of chronic hepatitis B: randomized trial in a predominantly homosexual male population.  Gastroenterology . 1995;  108 165-171
    CrossrefPubMedGoogle Scholar
  • 67 McDonald J A, Caruso L, Karayiannis P. et al . Diminished responsiveness of male homosexual chronic hepatitis B virus carriers with HTLV-III antibodies to recombinant alpha-interferon.  Hepatology . 1987;  7 719-723
    PubMedGoogle Scholar
  • 68 Di Martino V, Thevenot T, Boyer N, Degos F, Marcellin P. Serum alanine transaminase level is a good predictor of response to interferon alfa therapy for chronic hepatitis B in human immunodeficiency virus-infected patients.  Hepatology . 2000;  31 1030-1031
    PubMedGoogle Scholar
  • 69 Di Martino V, Lunel F, Cadranel J F. et al . Long-term effects of interferon-alpha in five HIV-positive patients with chronic hepatitis B.  J Viral Hepat . 1996;  3 253-260
    PubMedGoogle Scholar
  • 70 Marcellin P, Boyer N, Colin J F. et al . Recombinant alpha interferon for chronic hepatitis B in anti-HIV positive patients receiving zidovudine.  Gut . 1993;  34(Suppl 2) S106
    CrossrefPubMedGoogle Scholar
  • 71 Zylberberg H, Jiang J, Pialoux G. et al . Alpha-interferon for chronic active hepatitis B in human immunodeficiency virus-infected patients.  Gastroenterol Clin Biol . 1996;  20 968-971
    PubMedGoogle Scholar
  • 72 Visco G, Alba L, Grisetti S. et al . Zidovudine plus interferon alfa-2b treatment in patients with HIV and chronic active viral hepatitis.  Gut . 1993;  34(Suppl 2) S107-S108
    PubMedGoogle Scholar
  • 73 Fried M W, Shiffman M L, Reddy K R. et al . Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection.  N Engl J Med . 2002;  347 975-982
    CrossrefPubMedGoogle Scholar
  • 74 Cooksley W G, Piratvisuth T, Wang Y J. et al . 40 kDa peginterferon alfa-2A (PEGASYS): efficacy and safety results from a phase II, randomized actively controlled, multicenter study in the treatment of HBeAg positive chronic hepatitis B.  Hepatology . 2001;  34 349A
    PubMedGoogle Scholar
  • 75 Dienstag J L, Schiff E R, Wright T L. et al . Lamivudine as initial treatment for chronic hepatitis B in the United States.  N Engl J Med . 1999;  341 1256-1263
    CrossrefPubMedGoogle Scholar
  • 76 Lai C L, Chien R N, Leung N WY. et al . A one-year trial of lamivudine for chronic hepatitis B.  N Engl J Med . 1998;  339 61-68
    CrossrefPubMedGoogle Scholar
  • 77 Chien R N, Liaw Y F, Atkins M. Pretherapy alanine transaminase level as a determinant for hepatitis B e antigen seroconversion during lamivudine therapy in patients with chronic hepatitis B. Asian Hepatitis Lamivudine Trial Group.  Hepatology . 1999;  30 770-774
    CrossrefPubMedGoogle Scholar
  • 78 Song B C, Suh D J, Lee H C, Chung Y H, Lee Y S. Hepatitis B e antigen seroconversion after lamivudine therapy is not durable in patients with chronic hepatitis B in Korea.  Hepatology . 2000;  32 803-806
    CrossrefPubMedGoogle Scholar
  • 79 Pil H S, Kwang-Hyub H, Hoon A S. et al . Additional lamivudine therapy after HBeAg seroconversion would prolong the durability of response in HBV endemic area.  Hepatology . 2001;  34 322A
    PubMedGoogle Scholar
  • 80 Tassopoulos N C, 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. Lamivudine Precore Mutant Study Group.  Hepatology . 1999;  29 889-896
    CrossrefPubMedGoogle Scholar
  • 81 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;  125 705-712
    PubMedGoogle Scholar
  • 82 Dore G J, Cooper D A, 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;  180 607-613
    CrossrefPubMedGoogle Scholar
  • 83 Zollner B, Petersen J, Schroter M. et al . 20-fold increase in risk of lamivudine resistance in hepatitis B virus subtype adw.  Lancet . 2001;  357 934-935
    CrossrefPubMedGoogle Scholar
  • 84 Stuyver L J, Locarnini S A, Lok A. et al . Nomenclature for antiviral-resistant human hepatitis B virus mutations in the polymerase region.  Hepatology . 2001;  33 751-757
    CrossrefPubMedGoogle Scholar
  • 85 Thibault V, Aubron-Olivier C, Agut H, Katlama C. Primary infection with a lamivudine-resistant hepatitis B virus.  AIDS . 2002;  16 131-133
    CrossrefPubMedGoogle Scholar
  • 86 Benhamou Y, Bochet M, Thibault V. et al . Long-term incidence of hepatitis B virus resistance to lamivudine in human immunodeficiency virus-infected patients.  Hepatology . 1999;  30 1302-1306
    CrossrefPubMedGoogle Scholar
  • 87 Yuen M F, Sablon E, Hui C K. et al . Factors associated with hepatitis B virus DNA breakthrough in patients receiving prolonged lamivudine therapy.  Hepatology . 2001;  34 785-791
    CrossrefPubMedGoogle Scholar
  • 88 Lim S G, Wai C T, Rajnakova A, Kajiji T, Guan R. Fatal hepatitis B reactivation following discontinuation of nucleoside analogues for chronic hepatitis B.  Gut . 2002;  51 597-599
    CrossrefPubMedGoogle Scholar
  • 89 Liaw Y F, Leung N W, Chang T T. et al . Effects of extended lamivudine therapy in Asian patients with chronic hepatitis B. Asia Hepatitis Lamivudine Study Group.  Gastroenterology . 2000;  119 172-180
    CrossrefPubMedGoogle Scholar
  • 90 Peters M, Hann H W, Martin P. et al . Adefovir dipivoxil (ADV) alone and in combination with lamivudine (LAM) suppresses YMDD mutant hepatitis B virus replication: 48 week preliminary analysis.  Hepatology . 2002;  36 374A
    CrossrefPubMedGoogle Scholar
  • 91 Marcellin P, Chang T T, Lim S G. et al . Adefovir dipivoxil for the treatment of patients with HBe antigen-positive chronic hepatitis B.  New Engl J Med . 2003;  348 808-816
    CrossrefPubMedGoogle Scholar
  • 92 Werle B, Wursthorn K, Petersen J. et al . Quantitative analyses of hepatic HBV cccDNA during the natural history of chronic hepatitis B and adefovir dipivoxil therapy: an international, multicenter study.  Hepatology . 2002;  36 296A
    PubMedGoogle Scholar
  • 93 Xiung S, Yang H, Westland C. et al .Resistance surveillance of HBeAg-chronic hepatitis B patients treated for two years with adefovir dipivoxil. 11th International Symposium on Viral Hepatitis and Liver Disease, 2003, Abstract 779
    Google Scholar
  • 94 Benhamou Y, Bochet M, Thibault V. et al . Safety and efficacy of adefovir dipivoxil in patients co-infected with HIV-1 and lamivudine-resistant hepatitis B virus: an open-label pilot study.  Lancet . 2001;  358 718-723
    CrossrefPubMedGoogle Scholar
  • 95 Nunez M, Perez-Olmeda M, Diaz B. et al . Activity of tenofovir on hepatitis B virus replication in HIV-co- infected patients failing or partially responding to lamivudine.  AIDS . 2002;  16 2352-2354
    CrossrefPubMedGoogle Scholar
  • 96 Delaugerre C, Marcelin A G, Thibault V. et al . Human immunodeficiency virus (HIV) Type 1 reverse transcriptase resistance mutations in hepatitis B virus (HBV)-HIV-coinfected patients treated for HBV chronic infection once daily with 10 milligrams of adefovir dipivoxil combined with lamivudine.  Antimicrob Agents Chemother . 2002;  46 1586-1588
    CrossrefPubMedGoogle Scholar
  • 97 Chang T T, Hadziyannis S, Cianciara J. et al . Sustained viral load and ALT reduction following 48 weeks of entecavir treatment in subjects withchronic hepatitis B who have failed lamivudine.  Hepatology . 2002;  36 300A
    PubMedGoogle Scholar
  • 98 Gish R, Leung N W, Wang C. et al . Antiviral activity, safety, and incidence of resistance in chronically infected hepatitis B patients given once daily emtricitabine for 2 years.  Hepatology . 2002;  36 372A
    PubMedGoogle Scholar
  • 99 Lai C L, Leung N W, Teo E K. et al . International multicenter trial of LdT (telbividine) alone and in combination with lamivudine for chronic hepatitis B: an interim analysis.  Hepatology . 2002;  36 301A
    PubMedGoogle Scholar
  • 100 Barbaro G, Zechini F, Pellicelli A M. et al . Long-term efficacy of interferon alpha-2b and lamivudine in combination compared to lamivudine monotherapy in patients with chronic hepatitis B. An Italian multicenter, randomized trial.  J Hepatol . 2001;  35 406-411
    CrossrefPubMedGoogle Scholar
  • 101 Schalm S W, Heathcote J, Cianciara J. et al . Lamivudine and alpha interferon combination treatment of patients with chronic hepatitis B infection: a randomised trial.  Gut . 2000;  46 562-568
    CrossrefPubMedGoogle Scholar
  • 102 Markowitz J S, Martin P, Conrad A J. et al . Prophylaxis against hepatitis B recurrence following liver transplantation using combination lamivudine and hepatitis B immune globulin.  Hepatology . 1998;  28 585-589
    CrossrefPubMedGoogle Scholar