Skip to main content

Advertisement

Log in

Management of Hepatitis B Virus Coinfection: HIV, Hepatitis C Virus, Hepatitis D Virus

  • Hepatitis B: Epidemiology, Natural History, Treatment, and Transplantation (Thomas Berg and Steven-Huy Han, Section Editors)
  • Published:
Current Hepatitis Reports Aims and scope Submit manuscript

Abstract

Coinfection of hepatitis B virus (HBV) with HIV, hepatitis C virus (HCV) and hepatitis D virus (HDV) is common because of shared modes of transmission. Increasing prevalence of high risk sexual behavior and intra venous drug use (IVDU) contributes to a majority of the cases with coinfection. Occult HBV or prior HBV infection is frequently encountered in patients coinfected with HIV or HCV. Although HBV is a preventable disease, failure to screen and inadequate vaccination in the high risk individuals account for vast under-recognition of the cases with HBV infection. Chronic liver disease from viral hepatitis B and C has emerged as the major cause of morbidity and mortality worldwide as well as in the United States. This is especially true in cases coinfected with HIV. The potential long term risks of untreated hepatitis include cirrhosis and hepatocellular carcinoma. There have been several advancements in the understanding of natural history and management options of chronic viral hepatitis. This article discusses and reviews the natural history, epidemiology, and management of HBV patients coinfected with HIV, HCV, or HDV. It includes an updated summary of the outcomes with liver transplantation and post transplant recurrence in the coinfected population with HBV. It also discusses the role of occult HBV in HIV and HCV coinfection respectively.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

Papers of particular interest, published recently, have been highlighted as: •• Of major importance

  1. Kellerman SE, Hanson DL, McNaghten AD, Fleming PL. Prevalence of chronic hepatitis B and incidence of acute hepatitis B infection in human immunodeficiency virus-infected subjects. J Infect Dis. 2003;188(4):571–7.

    Article  PubMed  Google Scholar 

  2. Duclos-Vallee JC, Feray C, Sebagh M, et al. Liver transplantation in HIV-HCV and HIVHBV coinfected patients: a large experience in a single centre. J Hepatol. 2006;44:S8.

    Article  Google Scholar 

  3. Brook G, Main J, Nelson M, Bhagani S, Wilkins E, Leen C, et al. British HIV Association guidelines for the management of coinfection with HIV-1 and hepatitis B or C virus 2010. HIV Med. 2010;11(1):1–30.

    Article  PubMed  CAS  Google Scholar 

  4. Sulkowski MS. Viral hepatitis and HIV coinfection. J Hepatol. 2008;48(2):353–67.

    Article  PubMed  CAS  Google Scholar 

  5. Thio C, Seaberg E, Skolasky R, Phair J, Visscher B, Muñoz A, et al. HIV-1, hepatitis B virus, and risk of liver-related mortality in the Multicenter Cohort Study (MACS). Lancet. 2002;360:1921–6.

    Article  PubMed  Google Scholar 

  6. Konopnicki D, Mocroft A, de Wit S, Antunes F, Ledergerber B, Katlama C, et al. Hepatitis B and HIV: prevalence, AIDS progression, response to HAART and increased mortality in the EuroSIDA cohort. AIDS. 2005;19:2117–25.

    Article  Google Scholar 

  7. Sulkowski MS, Thomas DL, Mehta SH, Chaisson RE, Moore RD. Hepatotoxicity associated with nevirapine or efavirenz containing antiretroviral therapy: role of hepatitis C and B infections. Hepatology. 2002;35:182–9.

    Article  PubMed  CAS  Google Scholar 

  8. Iloeje U, Yang H, Su J, Jen C, You S, Chen C, et al. Predicting cirrhosis risk based on the level of circulating hepatitis B virus viral load. Gastroenterology. 2006;130:678–86.

    Article  PubMed  Google Scholar 

  9. Chen C, Yang H, Su J, Jen C, You S, Lu S, et al. Risk of hepatocellular carcinoma across biological gradient of serum hepatitis B virus DNA level. JAMA. 2006;295:65–73.

    Article  PubMed  CAS  Google Scholar 

  10. Chen CJ, Yang HI, Su J, Jen CL, You SL, et al. Risk of hepatocellular carcinoma across a biological gradient of serum hepatitis B virus DNA level. JAMA. 2006;295(1):65–73.

    Article  PubMed  CAS  Google Scholar 

  11. Weber R, Sabin CA, Friis-Møller N, Reiss P, El-Sadr WM, Kirk O, et al. Liver-related deaths in persons infected with the human immunodeficiency virus: the D:A:D study. Arch Intern Med. 2006;166(15):1632–41.

    Article  PubMed  Google Scholar 

  12. Cocciolone R, Morey A, Panasiuk P, Whitfeld MJ, et al. Atypical Gianotti-Crosti syndrome in two HIV and hepatitis B co-infected adults. Australas J Dermatol. 2011;52(1):32–6.

    Article  PubMed  Google Scholar 

  13. Mendes-Corrêa M, Núñez M, et al. Management of HIV and hepatitis virus coinfection. Expert Opin Pharmacother. 2010;11(15):2497–516.

    Article  PubMed  Google Scholar 

  14. Sulkowski MS et al. Viral hepatitis and HIV coinfection. J Hepatol. 2008;48(2):353–67.

    Article  PubMed  CAS  Google Scholar 

  15. Wursthorn K, Wedemeyer H, Manns MP. Republished paper: Managing HBV in patients with impaired immunity. Postgrad Med J. 2011;87(1025):223–38.

    Article  PubMed  Google Scholar 

  16. Cooper C, Kanters S, Klein M, Chaudhury P, Marotta P, Wong P, et al. Liver transplant outcomes in HIV-infected patients: a systematic review and meta-analysis with synthetic cohort. AIDS. 2011;25(6):777–86.

    Article  PubMed  Google Scholar 

  17. Tateo M, Roque-Afonso AM, Antonini TM, Medja F, Lombes A, Jardel C, et al. Long-term follow-up of liver transplanted HIV/ hepatitis B virus coinfected patients: perfect control of hepatitis B virus replication and absence of mitochondrial toxicity. AIDS. 2009;23:1069–76.

    Article  PubMed  Google Scholar 

  18. Roland ME, Stock PG. Liver transplantation in HIV infected recipients. Semin Liver Dis. 2006;26:273.

    Article  PubMed  Google Scholar 

  19. Solid organ transplantation in HIV: multi-site study. http://www.HIVtransplant.com. Accessed November 2007.

  20. •• Bagaglio S, Bianchi G, Danise A, Porrino L, Uberti-Foppa C. Longitudinal evaluation of occult hepatitis B infection in HIV1 infected individuals during highly active antiretroviral treatment interruption and after HAART resumption. Infection 2011;39(2):121–6. This prospective study showed that in HIV positive patients, occult hepatitis B did not cause significant flare of transaminases during anti retroviral therapy or when anti retroviral therapy is interrupted. No HBV resistance mutations were encountered even when the patients received HAART containing single agent against HBV.

    Article  PubMed  CAS  Google Scholar 

  21. Koff RS. Risks associated with hepatitis A and hepatitis B in patients with hepatitis C. J Clin Gastroenterol. 2001;33:20–6.

    Article  PubMed  CAS  Google Scholar 

  22. Chu CJ, Lee SD. Hepatitis B virus/hepatitis C virus coinfection: epidemiology, clinical features, viralinteractions and treatment. J Gastroenterol Hepatol. 2008;23(4):512–20.

    Article  PubMed  Google Scholar 

  23. Liaw YF, Chen YC, Sheen IS, Chien RN, Yeh CT, Chu CM. Impact of acute hepatitis C virus super-infection in patients with chronic hepatitis B virus infection. Gastroenterology. 2004;126:1024–9.

    Article  PubMed  Google Scholar 

  24. Pontisso P, Gerotto M, Ruvoletto MG, et al. Hepatitis C genotypes in patients with dual hepatitis B and C virus infection. J Med Virol. 1996;48:157–60.

    Article  PubMed  CAS  Google Scholar 

  25. Raimondo G, Brunetto MR, Pontisso P, et al. Longitudinal evaluation reveals a complex spectrum of virological profiles in hepatitis B virus/hepatitis C virus-co-infected patients. Hepatology. 2006;43:100–7.

    Article  PubMed  Google Scholar 

  26. Mimms LT, Mosley JW, Hollinger FB, et al. Effect of concurrent acute infection with hepatitis C virus on acute hepatitis B virus infection. BMJ. 1993;307:1095–7.

    Article  PubMed  CAS  Google Scholar 

  27. Coppola N, Marrocco C, Di Caprio D, et al. Acute hepatitis B and C virus coinfection: a virological and clinical study of 3 cases. Clin Infect Dis. 2003;36:528–32.

    Article  PubMed  Google Scholar 

  28. Liaw YF, Lin SM, Sheen IS, Chu CM. Acute hepatitis C virus superinfection followed by spontaneous HBeAg seroconversion and HBsAg elimination. Infection. 1991;19:250–1.

    Article  PubMed  CAS  Google Scholar 

  29. Liaw YF, Yeh CT, Tsai SL. Impact of acute hepatitis B virus superinfection on chronic hepatitis C virus infection. Am J Gastroenterol. 2000;95:2978–80.

    Article  PubMed  CAS  Google Scholar 

  30. Wietzke P, Schott P, Braun F, Mihm S, Ramadori G. Clearance of HCV RNA in a chronic hepatitis C virus-infected patient during acute hepatitis B virus super-infection. Liver. 1999;19:348–53.

    Article  PubMed  CAS  Google Scholar 

  31. Cacciola I, Pollicino T, Squadrito G, et al. Occult hepatitis B virus infection in patients with chronic hepatitis C liver disease. N Engl J Med. 1999;341:22–6.

    Article  PubMed  CAS  Google Scholar 

  32. Kao JH, Chen PJ, Lai MY, Chen DS. Occult hepatitis B virus infection and clinical outcomes of patients with chronic hepatitis C. J Clin Microbiol. 2002;40:4068–71.

    Article  PubMed  CAS  Google Scholar 

  33. •• Lok AS, Everhart JE, Di Bisceglie AM, Kim HY, et al. Occult and previous hepatitis B virus infection are not associated with hepatocellular carcinoma in US patients with chronic hepatitis C. Hepatology 2011;54(2):434–42. This large case-control study concluded that neither prior HBV infection nor occult HBV are associated with increased risk of HCC in patients with histologically advanced chronic HCV.

    Article  PubMed  Google Scholar 

  34. Sagnelli E, Coppola N, Pisaturo M, et al. HBV superinfection in HCV chronic carriers: a disease that is frequently severe but associated with the eradication of HCV. Hepatology. 2009;49:1090–7.

    Article  PubMed  CAS  Google Scholar 

  35. Chu CM, Sheen IS, Liaw YF. The role of hepatitis C virus in fulminant viral hepatitis in an area with endemic hepatitis A and B. Gastroenterology. 1994;107:189–95.

    PubMed  CAS  Google Scholar 

  36. Donato F, Boffetta P, Puoti M. A meta-analysis of epidemiological studies on the combined effect of hepatitis B and C virus infections in causing hepatocellular carcinoma. Int J Cancer. 1998;75:347–54.

    Article  PubMed  CAS  Google Scholar 

  37. Jamma S, Hussain G, Lau DT. Current concepts of HBV/HCV coinfection: coexistence, but not necessarily in harmony. Curr Hepat Rep. 2010;9(4):260–9.

    Article  PubMed  Google Scholar 

  38. Liu CJ, Chen PJ, Lai MY, et al. Ribavirin and interferon is effective for hepatitis C virus clearance in hepatitis B and C dually infected patients. Hepatology. 2003;37:568–76.

    Article  PubMed  CAS  Google Scholar 

  39. Potthoff A, Manns MP, Wedemeyer H. Treatment of HBV/HCV coinfection. Expert Opin Pharmacother. 2010;11(6):919–28.

    Article  PubMed  CAS  Google Scholar 

  40. Marrone A, Zampino R, D’Onofrio M, et al. Combined interferon plus lamivudine treatment in young patients with dual HBV (HBeAg positive) and HCV chronic infection. J Hepatol. 2004;41:1064–5.

    Article  PubMed  CAS  Google Scholar 

  41. •• Manzia TM, Di Paolo D, Sforza D, Toti L, Angelico R, Brega A, Angelico M, Tisone G. Liver transplantation for hepatitis B and C virus-related cirrhosis: mid-term results. Transplant Proc 2010; 42(4):1200–3. This retrospective study showed that recurrent fibrosis was lower in liver transplant recipients who were HBV-HCV coinfected than in those who are monoinfected with HBV or HCV alone.

    Article  PubMed  CAS  Google Scholar 

  42. Rizzetto M, Canese MG, Arico S, et al. Immunofluorescence detection of new antigen–antibody system (delta/anti-delta) associated to hepatitis B virus in liver and in serum of HBsAg carriers. Gut. 1977;18:997–1003.

    Article  PubMed  CAS  Google Scholar 

  43. Lai MM. RNA replication without RNA-dependent RNA polymerase: surprises from hepatitis delta virus. J Virol. 2005;79:7951–8.

    Article  PubMed  CAS  Google Scholar 

  44. Taylor JM. Chapter 3. Replication of the hepatitis delta virus RNA genome. Adv Virus Res. 2009;74:103–21.

    Article  PubMed  CAS  Google Scholar 

  45. Su CW, Huang YH, Huo TI, et al. Genotypes and viremia of hepatitis B and D viruses are associated with outcomes of chronic hepatitis D patients. Gastroenterology. 2006;130:1625–35.

    Article  PubMed  CAS  Google Scholar 

  46. Grabowski J, Wedemeyer H. Hepatitis delta: immunopathogenesis and clinical challenges. Dig Dis. 2010;28:133–8.

    Article  PubMed  Google Scholar 

  47. Lai MM. Hepatitis delta virus. In: Webster RG, Granoff A, editors. Encyclopedia of virology. London: Academic Press Ltd; 1994. p. 574–80.

    Google Scholar 

  48. Wedemeyer H, Manns MP. Epidemiology, pathogenesis and management of hepatitis D: update and challenges ahead. Nat Rev Gastroenterol Hepatol. 2010;7:31–40.

    Article  PubMed  Google Scholar 

  49. Castellares C, Barreiro P, Martin-Carbonero L, Labarga P, Vispo E, Casado R, et al. Liver cirrhosis in HIV-infected patients: prevalence, aetiology and clinical outcome. J Viral Hepat. 2008;15:165–72.

    PubMed  CAS  Google Scholar 

  50. Nikolopoulos G, Paraskevis D, Hatzitheodorou E, Moschidis Z, Sypsa V, Zavitsanos X, et al. Impact of hepatitis B virus infection on the progression of AIDS and mortality in HIV-infected individuals: a cohort study and meta-analysis. Clin Infect Dis. 2009;48:1763–71.

    Article  PubMed  Google Scholar 

  51. Dore G, Soriano V, Rockstroh J, Kupfer B, Tedaldi E, Peters L, et al. Frequent hepatitis B virus rebound among HIV-hepatitis B virus-coinfected patients following antiretroviral therapy interruption. AIDS. 2010;24:857–65.

    Article  PubMed  Google Scholar 

  52. Sulkowski MS. Hepatocellular carcinoma in HIV-infected patients comes of age: The convergence of epidemiology and treatment effectiveness. Journal of Hepatology 2009;50:736–745.

    Google Scholar 

  53. Raimondo G, Pollicino T, Cacciola I, Squadrito G. Occult hepatitis B virus infection. J Hepatol 2007;46:160–70.

    Google Scholar 

  54. Zhou J, Dore GJ, Zhang F, et al. Hepatitis B and C virus coinfection in the TREAT Asia HIV Observational Database. J Gastroenterol Hepatol. 2007;22:1510–8.

    Article  PubMed  Google Scholar 

  55. Soriano V, Garcia-Samaniego J, Valencia E, et al. Impact of chronic liver disease due to hepatitis viruses as cause of hospital admission and death in HIV-infected drug users. Eur J Epidemiol. 1999;15:1–4.

    Article  PubMed  CAS  Google Scholar 

  56. Lok ASF, McMahon BJ. AASLD practice guidelines. Chronic hepatitis B: update. 2009. Hepatology. 2009;50:1–36.

    Google Scholar 

  57. Chisari FV. Rous-Whipple Award Lecture. Viruses, immunity, and cancer: lessons from hepatitis B. Am J Pathol. 2000;156:1117e32.

    Article  Google Scholar 

  58. Terrault N, Roche B, Samuel D. Management of the hepatitis B virus in the liver transplantation setting: a European and an American perspective. Liver Transpl. 2005;11:716e32.

    Article  Google Scholar 

  59. Weber R. Liver-related deaths in persons infected with the human immunodeficiency virus - The D: A: D study. Arch Intern Med. 2006;166:1632e41.

    Google Scholar 

  60. Rodriguez-Torres M, Rodriguez-Orengo JF, Rios-Bedoya CF, et al. Efficacy and safety of peg-IFN alfa-2a with ribavirin for the treatment of HCV/HIV coinfected patients who failed previous IFN based therapy. J Clin Virol. 2007;38:32–8.

    Article  PubMed  CAS  Google Scholar 

  61. Berenguer M. Natural history of recurrent hepatitis C. Liver Transplantation. 2002;8:S14–8.

    Article  PubMed  Google Scholar 

  62. Testa G, Crippin JS, Netto GJ, Goldstein RM, Jennings LW, Brkic BS, et al. Liver transplantation for hepatitis C: recurrence and disease progression in 300 patients. Liver Transplantation. 2000;6:553–61.

    Article  PubMed  CAS  Google Scholar 

  63. Roland ME, Barin B, Carlson L, Frassetto LA, Terrault NA, Hirose R, et al. HIV-infected liver and kidney transplant recipients: 1- and 3-year outcomes. Am J Transplant. 2008;8:355–65.

    Article  PubMed  CAS  Google Scholar 

  64. Castellares C, Barreiro P, Martin-Carbonero L, Labarga P, Vispo E, Casado R, et al. Liver cirrhosis in HIV-infected patients: prevalence, aetiology and clinical outcome. J Viral Hepat. 2008;15:165–72.

    PubMed  CAS  Google Scholar 

  65. Shire NJ, Rouster SD, Rajicic N, Sherman KE. Occult hepatitis B in HIV-infected patients. J Acquir Immune Defic Syndr. 2004;36:869–75.

    Article  PubMed  Google Scholar 

  66. Genné D, Rossi I. Hepatitis delta in Switzerland: a silent epidemic. Swiss Med Wkly. 2011;141:w13176.

    PubMed  Google Scholar 

  67. •• Niro GA, Smedile A, Ippolito AM, et al. Outcome of chronic D hepatitis in Italy: a long-term cohort study. J Hepatol 2010;53:834–40. This retrospective cohort study underscores the role of early treatment in patients with chronic HDV. Interferon treatment was associated with better survival outcomes and reduction of major complications by slowing the natural course of the liver disease.

    Article  PubMed  Google Scholar 

  68. Rizzetto M. Hepatitis D: virology, clinical and epidemiological aspects. Acta Gastroenterol Belg. 2000;63:221–4.

    PubMed  CAS  Google Scholar 

  69. Andersen ES, Gerstoft J, Weis N. Reactivation of hepatitis D virus after chemotherapy for diffuse large B cell lymphomadespite lamivudine prophylaxis. Int J Hematol. 2010;92(2):378–80.

    Article  PubMed  Google Scholar 

  70. •• Wedemeyer H, Yurdaydìn C, Dalekos GN, Erhardt A, Çakaloğlu Y, Değertekin H, Gürel S, Zeuzem S, Zachou K, Bozkaya H, Koch A, Bock T, Dienes HP, Manns MP; HIDIT Study Group. Peginterferon plus adefovir versus either drug alone for hepatitis delta. N Engl J Med 2011;364(4):322–31. This randomized controlled trial showed that pegylated interferon treatment for 48 weeks in chronic HDV patients resulted in sustained viral response in more than 25% and biochemical response in 40% of patients. Although addition of adefovir to pegylated interferon had similar outcomes as pegylated interferon alone, there was a significant decrease in HBsAg titers in the former group. Treatment with adefovir alone was ineffective.

    Article  PubMed  CAS  Google Scholar 

  71. Erhardt A, Gerlich W, Starke C, et al. Treatment of chronic hepatitis delta with pegylated interferon-alpha2b. Liver Int. 2006;26:805–10.

    Article  PubMed  CAS  Google Scholar 

  72. Castelnau C, Le Gal F, Ripault MP, et al. Efficacy of peginterferon alpha-2b in chronic hepatitis delta: relevance of quantitative RT-PCR for follow-up. Hepatology. 2006;44:728–35.

    Article  PubMed  CAS  Google Scholar 

  73. Mederacke I, Bremer B, Heidrich B, et al. Establishment of a novel quantitative hepatitis D virus (HDV) RNA assay using the Cobas TaqMan platform to study HDV RNA kinetics. J Clin Microbiol. 2010;48:2022–9.

    Article  PubMed  CAS  Google Scholar 

  74. Wedemeyer H, Tillmann HL, Tegtmeyer B, Cornberg M, Schuler A, Liermann H, et al. Infection with multiple hepatitis viruses: evidence for suppression of HCV replication by HDV and HBV. Hepatology. 2001;34:200.

    Google Scholar 

  75. Heidrich B, Deterding K, Tillmann HL, Raupach R, Manns MP, Wedemeyer H. Virological and clinical characteristics of delta hepatitis in Central Europe. J Viral Hepat. 2009;16:883–94.

    Article  PubMed  CAS  Google Scholar 

  76. Smedile A, Casey JL, Cote PJ, et al. Hepatitis D viremia following orthotopic liver transplantation involves a typical HDV virion with a hepatitis B surface antigen envelope. Hepatology. 1998;27:1723–9.

    Article  PubMed  CAS  Google Scholar 

  77. Niro GA, Gioffreda D, Fontana R. Hepatitis delta virus infection: open issues. Dig Liver Dis. 2011;43 Suppl 1:S19–24.

    Article  PubMed  Google Scholar 

  78. Yurdaydın C, Idilman R, Bozkaya H, Bozdayi AM. Natural history and treatment of chronic delta hepatitis. J Viral Hepat. 2010;17(11):749–56.

    Article  PubMed  Google Scholar 

  79. Niro GA, Ciancio A, Tillman HL, et al. Lamivudine therapy in chronic delta hepatitis: a multicentre randomized-controlled pilot study. Aliment Pharmacol Ther. 2005;22:227–32.

    Article  PubMed  CAS  Google Scholar 

  80. Glenn JS. Prenylation of HDAg and antiviral drug development. Curr Top Microbiol Immunol. 2006;307:133–49.

    Article  PubMed  CAS  Google Scholar 

  81. Mederacke I, Wedemeyer H. Nitazoxanide for the treatment of chronic hepatitis C new opportunities but new challenges? Ann Hepatol. 2009;8:166–8.

    PubMed  Google Scholar 

  82. Chiaramonte M, Stroffolini T, Vian A, et al. Rate of incidence of hepatocellular carcinoma in patients with compensated viral cirrhosis. Cancer 1999;85:2132–7.

    Google Scholar 

Download references

Disclosure

No potential conflicts of interest relevant to this article were reported.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Douglas Dieterich.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Bhamidimarri, K.R., Park, J. & Dieterich, D. Management of Hepatitis B Virus Coinfection: HIV, Hepatitis C Virus, Hepatitis D Virus. Curr Hepatitis Rep 10, 262–268 (2011). https://doi.org/10.1007/s11901-011-0115-1

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11901-011-0115-1

Keywords

Navigation