Skip to main content

Advertisement

SpringerLink
Log in

Epidemiology, Natural History, and Treatment of Hepatitis Delta Virus Infection in HIV/Hepatitis B Virus Coinfection

  • Co-infections and Comorbidity (D Bhattacharya, Section Editor)
  • Published:
Current HIV/AIDS Reports Aims and scope Submit manuscript

Abstract

Purpose of Review

Limited data exist on the prevalence, determinants, and outcomes of hepatitis delta virus (HDV) infection among HIV/hepatitis B virus (HBV)–coinfected persons. This review provides current evidence on the epidemiology, natural history, and treatment of HDV infection in patients with HIV/HBV coinfection and highlights future research needs.

Recent Findings

Cross-sectional studies in Europe, Africa, South America, and Asia show that the prevalence of HDV among HIV/HBV-coinfected patients ranges from 1.2 to 25%. No studies have evaluated the prevalence of HDV infection among HIV/HBV-coinfected patients in the USA. HDV infection increases the risk of hepatic decompensation and hepatocellular carcinoma among HIV/HBV-coinfected patients. HDV treatment remains limited to pegylated interferon-alpha, which results in sustained virologic response in fewer than 25%.

Summary

Data on the epidemiology, natural history, and treatment of HDV among HIV/HBV-coinfected persons remain limited. More research is needed to address these knowledge gaps in order to better manage HDV coinfection in HIV/HBV-coinfected patients.

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

Access this article

Log in via an institution

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 importance •• Of major importance

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

    PubMed  Google Scholar 

  2. Hughes SA, Wedemeyer H, Harrison PM. Hepatitis delta virus. Lancet. 2011;378(9785):73–85.

    PubMed  Google Scholar 

  3. Rizzetto M. Hepatitis D: thirty years after. J Hepatol. 2009;50(5):1043–50.

    CAS  PubMed  Google Scholar 

  4. •• Chen HY, Shen DT, Ji DZ, et al. Prevalence and burden of hepatitis D virus infection in the global population: a systematic review and meta-analysis. Gut. 2018;68:512–21. This systematic review and meta-analysis found that the prevalence of HDV among HBsAg-positive individuals may be higher than was previously reported.

    PubMed  Google Scholar 

  5. Rizzetto M. Hepatitis D virus: introduction and epidemiology. Cold Spring Harb Perspect Med. 2015;5(7):a021576.

    PubMed  PubMed Central  Google Scholar 

  6. Wedemeyer H, Heidrich B, Manns MP. Hepatitis D virus infection--not a vanishing disease in Europe! Hepatology. 2007;45(5):1331–2 author reply 2-3.

    PubMed  Google Scholar 

  7. Erhardt A, Knuth R, Sagir A, Kirschberg O, Heintges T, Häussinger D. Socioepidemiological data on hepatitis delta in a German university clinic--increase in patients from Eastern Europe and the former Soviet Union. Z Gastroenterol. 2003;41(6):523–6.

    CAS  PubMed  Google Scholar 

  8. Cross TJ, Rizzi P, Horner M, et al. The increasing prevalence of hepatitis delta virus (HDV) infection in South London. J Med Virol. 2008;80(2):277–82.

    PubMed  Google Scholar 

  9. •• Béguelin C, Moradpour D, Sahli R, et al. Hepatitis delta-associated mortality in HIV/HBV-coinfected patients. J Hepatol. 2017;66(2):297–303. This cross-sectional study found the prevalence of HDV infection to be 15.45% in the Swiss HIV Cohort Study.

    PubMed  Google Scholar 

  10. Kushner T, Serper M, Kaplan DE. Delta hepatitis within the veterans affairs medical system in the United States: prevalence, risk factors, and outcomes. J Hepatol. 2015;63(3):586–92.

    PubMed  PubMed Central  Google Scholar 

  11. Wedemeyer H, Yurdaydìn C, Dalekos GN, Erhardt A, Çakaloğlu Y, Değertekin H, et al. Peginterferon plus adefovir versus either drug alone for hepatitis delta. N Engl J Med. 2011;364(4):322–31.

    CAS  PubMed  Google Scholar 

  12. • Terrault NA, Lok ASF, McMahon BJ, et al. Update on prevention, diagnosis, and treatment of chronic Hepatitis B: AASLD 2018 Hepatitis B Guidance. Clin Liver Dis (Hoboken). 2018;12(1):33–4. These are the most updated American Association for the Study of Liver Disease guidelines on hepatitis B virus management.

    Google Scholar 

  13. EASL 2017 Clinical Practice Guidelines on the management of hepatitis B virus infection. J Hepatol. 2017;67(2):370–98.

  14. Sarin SK, Kumar M, Lau GK, Abbas Z, Chan HLY, Chen CJ, et al. Asian-Pacific clinical practice guidelines on the management of hepatitis B: a 2015 update. Hepatol Int. 2016;10(1):1–98.

    CAS  PubMed  Google Scholar 

  15. Soriano V, Grint D, d'Arminio Monforte A, et al. Hepatitis delta in HIV-infected individuals in Europe. AIDS. 2011;25(16):1987–92.

    PubMed  Google Scholar 

  16. Hønge BL, Jespersen S, Medina C, Té DS, da Silva ZJ, Lewin S, et al. Hepatitis B and delta virus are prevalent but often subclinical co-infections among HIV infected patients in Guinea-Bissau, West Africa: a cross-sectional study. PLoS One. 2014;9(6):e99971.

    PubMed  PubMed Central  Google Scholar 

  17. Buti M, Homs M, Rodriguez-Frias F, Funalleras G, Jardí R, Sauleda S, et al. Clinical outcome of acute and chronic hepatitis delta over time: a long-term follow-up study. J Viral Hepat. 2011;18(6):434–42.

    CAS  PubMed  Google Scholar 

  18. Romeo R, Del Ninno E, Rumi M, et al. A 28-year study of the course of hepatitis delta infection: a risk factor for cirrhosis and hepatocellular carcinoma. Gastroenterology. 2009;136(5):1629–38.

    PubMed  Google Scholar 

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

    PubMed  Google Scholar 

  20. Gheorghe L, Iacob S, Simionov I, Vadan R, Gheorghe C, Iacob R, et al. Natural history of compensated viral B and D cirrhosis. Rom J Gastroenterol. 2005;14(4):329–35.

    PubMed  Google Scholar 

  21. Fattovich G, Giustina G, Christensen E, Pantalena M, Zagni I, Realdi G, et al. Influence of hepatitis delta virus infection on morbidity and mortality in compensated cirrhosis type B. The European concerted action on viral hepatitis (Eurohep). Gut. 2000;46(3):420–6.

    CAS  PubMed  PubMed Central  Google Scholar 

  22. Ji J, Sundquist K, Sundquist J. A population-based study of hepatitis D virus as potential risk factor for hepatocellular carcinoma. J Natl Cancer Inst. 2012;104(10):790–2.

    PubMed  Google Scholar 

  23. Fattovich G, Boscaro S, Noventa F, Pornaro E, Stenico D, Alberti A, et al. Influence of hepatitis delta virus infection on progression to cirrhosis in chronic hepatitis type B. J Infect Dis. 1987;155(5):931–5.

    CAS  PubMed  Google Scholar 

  24. Rizzetto M, Canese MG, Aricò 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(12):997–1003.

    CAS  PubMed  PubMed Central  Google Scholar 

  25. Grabowski J, Wedemeyer H. Hepatitis delta: immunopathogenesis and clinical challenges. Dig Dis. 2010;28(1):133–8.

    PubMed  Google Scholar 

  26. He W, Ren B, Mao F, Jing Z, Li Y, Liu Y, et al. Hepatitis D virus infection of mice expressing human sodium taurocholate co-transporting polypeptide. PLoS Pathog. 2015;11(4):e1004840.

    PubMed  PubMed Central  Google Scholar 

  27. Verrier ER, Colpitts CC, Bach C, Heydmann L, Weiss A, Renaud M, et al. A targeted functional RNA interference screen uncovers glypican 5 as an entry factor for hepatitis B and D viruses. Hepatology. 2016;63(1):35–48.

    CAS  PubMed  Google Scholar 

  28. Li J, Wands J. Hepatitis B and D viral receptors. Hepatology. 2016;63(1):11–3.

    PubMed  Google Scholar 

  29. Chang J, Nie X, Chang HE, Han Z, Taylor J. Transcription of hepatitis delta virus RNA by RNA polymerase II. J Virol. 2008;82(3):1118–27.

    CAS  PubMed  Google Scholar 

  30. Koh C, Canini L, Dahari H, Zhao X, Uprichard SL, Haynes-Williams V, et al. Oral prenylation inhibition with lonafarnib in chronic hepatitis D infection: a proof-of-concept randomised, double-blind, placebo-controlled phase 2A trial. Lancet Infect Dis. 2015;15(10):1167–74.

    CAS  PubMed  PubMed Central  Google Scholar 

  31. Wedemeyer HPK, Deterding K, et al. A phase 2 dose-escalation study of lonafarnib plus ritonavir in patients with chronic hepatitis D: final results from the Lonafarnib with ritonavir in HDV-4 (LOWR HDV-4) study. J Hepatol. 2017;66(1):S24.

    Google Scholar 

  32. 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(6):1625–35.

    CAS  PubMed  Google Scholar 

  33. Casey JL, Niro GA, Engle RE, Vega A, Gomez H, McCarthy M, et al. Hepatitis B virus (HBV)/hepatitis D virus (HDV) coinfection in outbreaks of acute hepatitis in the Peruvian Amazon basin: the roles of HDV genotype III and HBV genotype F. J Infect Dis. 1996;174(5):920–6.

    CAS  PubMed  Google Scholar 

  34. Gomes-Gouvêa MS, Soares MC, Bensabath G, et al. Hepatitis B virus and hepatitis delta virus genotypes in outbreaks of fulminant hepatitis (Labrea black fever) in the western Brazilian Amazon region. J Gen Virol. 2009;90(Pt 11):2638–43.

    PubMed  Google Scholar 

  35. Guilhot S, Huang SN, Xia YP, La Monica N, Lai MM, Chisari FV. Expression of the hepatitis delta virus large and small antigens in transgenic mice. J Virol. 1994;68(2):1052–8.

    CAS  PubMed  PubMed Central  Google Scholar 

  36. Govindarajan S, De Cock KM, Redeker AG. Natural course of delta superinfection in chronic hepatitis B virus-infected patients: histopathologic study with multiple liver biopsies. Hepatology. 1986;6(4):640–4.

    CAS  PubMed  Google Scholar 

  37. Liao B, Zhang F, Lin S, He H, Liu Y, Zhang J, et al. Epidemiological, clinical and histological characteristics of HBV/HDV co-infection: a retrospective cross-sectional study in Guangdong, China. PLoS One. 2014;9(12):e115888.

    PubMed  PubMed Central  Google Scholar 

  38. Nisini R, Paroli M, Accapezzato D, Bonino F, Rosina F, Santantonio T, et al. Human CD4+ T-cell response to hepatitis delta virus: identification of multiple epitopes and characterization of T-helper cytokine profiles. J Virol. 1997;71(3):2241–51.

    CAS  PubMed  PubMed Central  Google Scholar 

  39. Roingeard P, Dubois F, Marcellin P, Bernuau J, Bonduelle S, Benhamou JP, et al. Persistent delta antigenaemia in chronic delta hepatitis and its relation with human immunodeficiency virus infection. J Med Virol. 1992;38(3):191–4.

    CAS  PubMed  Google Scholar 

  40. Bichko V, Netter HJ, Wu TT, Taylor J. Pathogenesis associated with replication of hepatitis delta virus. Infect Agents Dis. 1994;3(2–3):94–7.

    CAS  PubMed  Google Scholar 

  41. Samuel D, Zignego AL, Reynes M, Feray C, Arulnaden JL, David MF, et al. Long-term clinical and virological outcome after liver transplantation for cirrhosis caused by chronic delta hepatitis. Hepatology. 1995;21(2):333–9.

    CAS  PubMed  Google Scholar 

  42. Raimondo G, Brunetto MR, Pontisso P, Smedile A, Maina AM, Saitta C, et al. Longitudinal evaluation reveals a complex spectrum of virological profiles in hepatitis B virus/hepatitis C virus-coinfected patients. Hepatology. 2006;43(1):100–7.

    PubMed  Google Scholar 

  43. Arribas JR, González-García JJ, Lorenzo A, Montero D, de Guevara CL, Montes M, et al. Single (B or C), dual (BC or BD) and triple (BCD) viral hepatitis in HIV-infected patients in Madrid, Spain. AIDS. 2005;19(13):1361–5.

    CAS  PubMed  Google Scholar 

  44. Mathurin P, Thibault V, Kadidja K, Ganne-Carrié N, Moussalli J, el Younsi M, et al. Replication status and histological features of patients with triple (B, C, D) and dual (B, C) hepatic infections. J Viral Hepat. 2000;7(1):15–22.

    CAS  PubMed  Google Scholar 

  45. Jardi R, Rodriguez F, Buti M, Costa X, Cotrina M, Galimany R, et al. Role of hepatitis B, C, and D viruses in dual and triple infection: influence of viral genotypes and hepatitis B precore and basal core promoter mutations on viral replicative interference. Hepatology. 2001;34(2):404–10.

    CAS  PubMed  Google Scholar 

  46. Smedile A, Dentico P, Zanetti A, Sagnelli E, Nordenfelt E, Actis GC, et al. Infection with the delta agent in chronic HBsAg carriers. Gastroenterology. 1981;81(6):992–7.

    CAS  PubMed  Google Scholar 

  47. Pontisso P, Ruvoletto MG, Fattovich G, Chemello L, Gallorini A, Ruol A, et al. Clinical and virological profiles in patients with multiple hepatitis virus infections. Gastroenterology. 1993;105(5):1529–33.

    CAS  PubMed  Google Scholar 

  48. Wranke A, Heidrich B, Ernst S, Calle Serrano B, Caruntu FA, Curescu MG, et al. Anti-HDV IgM as a marker of disease activity in hepatitis delta. PLoS One. 2014;9(7):e101002.

    PubMed  PubMed Central  Google Scholar 

  49. Farci P, Gerin JL, Aragona M, Lindsey I, Crivelli O, Balestrieri A, et al. Diagnostic and prognostic significance of the IgM antibody to the hepatitis delta virus. JAMA. 1986;255(11):1443–6.

    CAS  PubMed  Google Scholar 

  50. Borghesio E, Rosina F, Smedile A, Lagget M, Niro MG, Marinucci G, et al. Serum immunoglobulin M antibody to hepatitis D as a surrogate marker of hepatitis D in interferon-treated patients and in patients who underwent liver transplantation. Hepatology. 1998;27(3):873–6.

    CAS  PubMed  Google Scholar 

  51. Shattock AG, Morris MC. Evaluation of commercial enzyme immunoassays for detection of hepatitis delta antigen and anti-hepatitis delta virus (HDV) and immunoglobulin M anti-HDV antibodies. J Clin Microbiol. 1991;29(9):1873–6.

    CAS  PubMed  PubMed Central  Google Scholar 

  52. Aragona M, Macagno S, Caredda F, Crivelli O, Lavarini C, Maran E, et al. Serological response to the hepatitis delta virus in hepatitis D. Lancet. 1987;1(8531):478–80.

    CAS  PubMed  Google Scholar 

  53. Noureddin M, Gish R. Hepatitis delta: epidemiology, diagnosis and management 36 years after discovery. Curr Gastroenterol Rep. 2014;16(1):365.

    PubMed  Google Scholar 

  54. Le Gal F, Brichler S, Sahli R, Chevret S, Gordien E. First international external quality assessment for hepatitis delta virus RNA quantification in plasma. Hepatology. 2016;64(5):1483–94.

    PubMed  Google Scholar 

  55. Olivero A, Smedile A. Hepatitis delta virus diagnosis. Semin Liver Dis. 2012;32(3):220–7.

    PubMed  Google Scholar 

  56. Schaper M, Rodriguez-Frias F, Jardi R, Tabernero D, Homs M, Ruiz G, et al. Quantitative longitudinal evaluations of hepatitis delta virus RNA and hepatitis B virus DNA shows a dynamic, complex replicative profile in chronic hepatitis B and D. J Hepatol. 2010;52(5):658–64.

    CAS  PubMed  Google Scholar 

  57. Zachou K, Yurdaydin C, Drebber U, Dalekos GN, Erhardt A, Cakaloglu Y, et al. Quantitative HBsAg and HDV-RNA levels in chronic delta hepatitis. Liver Int. 2010;30(3):430–7.

    CAS  PubMed  Google Scholar 

  58. Manesis EK, Vourli G, Dalekos G, Vasiliadis T, Manolaki N, Hounta A, et al. Prevalence and clinical course of hepatitis delta infection in Greece: a 13-year prospective study. J Hepatol. 2013;59(5):949–56.

    PubMed  Google Scholar 

  59. Negro F. Hepatitis D virus coinfection and superinfection. Cold Spring Harb Perspect Med. 2014;4(11):a021550.

    PubMed  PubMed Central  Google Scholar 

  60. Rizzetto M, Alavian SM. Hepatitis delta: the rediscovery. Clin Liver Dis. 2013;17(3):475–87.

    PubMed  Google Scholar 

  61. Amougou MA, Noah DN, Moundipa PF, Pineau P, Njouom R. A prominent role of hepatitis D virus in liver cancers documented in Central Africa. BMC Infect Dis. 2016;16(1):647.

    PubMed  PubMed Central  Google Scholar 

  62. Hadziyannis SJ. Review: hepatitis delta. J Gastroenterol Hepatol. 1997;12(4):289–98.

    CAS  PubMed  Google Scholar 

  63. Rizzetto M, Ponzetto A, Forzani I. Hepatitis delta virus as a global health problem. Vaccine. 1990;8 Suppl:S10–4 discussion S21–3.

    CAS  PubMed  Google Scholar 

  64. Braga WS, Castilho MC, Borges FG, et al. Hepatitis D virus infection in the Western Brazilian Amazon - far from a vanishing disease. Rev Soc Bras Med Trop. 2012;45(6):691–5.

    PubMed  Google Scholar 

  65. Lin HH, Lee SS, Yu ML, et al. Changing hepatitis D virus epidemiology in a hepatitis B virus endemic area with a national vaccination program. Hepatology. 2015;61(6):1870–9.

    CAS  PubMed  Google Scholar 

  66. •• Elsaid MI, Li Y, John T, Narayanan N, Catalano C, Rustgi VK. Economic and healthcare burdens of hepatitis delta: a study of commercially insured adults in the United States. Hepatology. 2019. Available from: https://doi.org/10.1002/hep.31055. This was a case control study that utilized claims data to determine the economic burden of HDV infection, and found that HDV infection was associated with increased healthcare costs.

  67. Gaeta GB, Precone DF, Cozzi-Lepri A, Cicconi P, D'Arminio MA. Multiple viral infections. J Hepatol. 2006;44(1 Suppl):S108–13.

    CAS  PubMed  Google Scholar 

  68. Sagnelli E, Stroffolini T, Ascione A, Chiaramonte M, Craxì A, Giusti G, et al. Decrease in HDV endemicity in Italy. J Hepatol. 1997;26(1):20–4.

    CAS  PubMed  Google Scholar 

  69. Navascués CA, Rodríguez M, Sotorrío NG, Sala P, Linares A, Suárez A, et al. Epidemiology of hepatitis D virus infection: changes in the last 14 years. Am J Gastroenterol. 1995;90(11):1981–4.

    PubMed  Google Scholar 

  70. Değertekin H, Yalçin K, Yakut M. The prevalence of hepatitis delta virus infection in acute and chronic liver diseases in Turkey: an analysis of clinical studies. Turk J Gastroenterol. 2006;17(1):25–34.

    PubMed  Google Scholar 

  71. Gaeta GB, Stroffolini T, Smedile A, Niro G, Mele A. Hepatitis delta in Europe: vanishing or refreshing? Hepatology. 2007;46(4):1312–3.

    PubMed  Google Scholar 

  72. Nath N, Mushahwar IK, Fang CT, Berberian H, Dodd RY. Antibodies to delta antigen in asymptomatic hepatitis B surface antigen-reactive blood donors in the United States and their association with other markers of hepatitis B virus. Am J Epidemiol. 1985;122(2):218–25.

    CAS  PubMed  Google Scholar 

  73. Safaie P, Razeghi S, Rouster SD, Privitera I, Sherman KE. Hepatitis D diagnostics: utilization and testing in the United States. Virus Res. 2018;250:114–7.

    CAS  PubMed  Google Scholar 

  74. Gish RG, Yi DH, Kane S, Clark M, Mangahas M, Baqai S, et al. Coinfection with hepatitis B and D: epidemiology, prevalence and disease in patients in Northern California. J Gastroenterol Hepatol. 2013;28(9):1521–5.

    PubMed  Google Scholar 

  75. •• Patel EU, Thio CL, Boon D, Thomas DL, Tobian AAR. Prevalence of hepatitis B and hepatitis D virus infections in the United States, 2011–2016. Clin Infect Dis. 2019;69(4):709–12. This cross-sectional study found that 42% of HBsAg-positive individuals are HDV antibody positive.

    PubMed  PubMed Central  Google Scholar 

  76. Kucirka LM, Farzadegan H, Feld JJ, Mehta SH, Winters M, Glenn JS, et al. Prevalence, correlates, and viral dynamics of hepatitis delta among injection drug users. J Infect Dis. 2010;202(6):845–52.

    PubMed  PubMed Central  Google Scholar 

  77. Ponzetto A, Seeff LB, Buskell-Bales Z, Ishak KG, Hoofnagle JH, Zimmerman HJ, et al. Hepatitis B markers in United States drug addicts with special emphasis on the delta hepatitis virus. Hepatology. 1984;4(6):1111–5.

    CAS  PubMed  Google Scholar 

  78. Novick DM, Farci P, Croxson TS, Taylor MB, Schneebaum CW, Lai ME, et al. Hepatitis D virus and human immunodeficiency virus antibodies in parenteral drug abusers who are hepatitis B surface antigen positive. J Infect Dis. 1988;158(4):795–803.

    CAS  PubMed  Google Scholar 

  79. 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.

    PubMed  Google Scholar 

  80. Konopnicki D, Mocroft A, de Wit S, Antunes F, Ledergerber B, Katlama C, et al. Hepatitis B and HIV: prevalence, AIDS progression, response to highly active antiretroviral therapy and increased mortality in the EuroSIDA cohort. AIDS. 2005;19(6):593–601.

    PubMed  Google Scholar 

  81. Lee HC, Ko NY, Lee NY, Chang CM, Ko WC. Seroprevalence of viral hepatitis and sexually transmitted disease among adults with recently diagnosed HIV infection in Southern Taiwan, 2000-2005: upsurge in hepatitis C virus infections among injection drug users. J Formos Med Assoc. 2008;107(5):404–11.

    PubMed  Google Scholar 

  82. Diop-Ndiaye H, Touré-Kane C, Etard JF, Lô G, Diaw PA, Ngom-Gueye NF, et al. Hepatitis B, C seroprevalence and delta viruses in HIV-1 Senegalese patients at HAART initiation (retrospective study). J Med Virol. 2008;80(8):1332–6.

    CAS  PubMed  Google Scholar 

  83. Nyirenda M, Beadsworth MB, Stephany P, et al. Prevalence of infection with hepatitis B and C virus and coinfection with HIV in medical inpatients in Malawi. J Inf Secur. 2008;57(1):72–7.

    CAS  Google Scholar 

  84. Kourtis AP, Bulterys M, Hu DJ, Jamieson DJ. HIV-HBV coinfection--a global challenge. N Engl J Med. 2012;366(19):1749–52.

    CAS  PubMed  PubMed Central  Google Scholar 

  85. Fernández-Montero JV, Vispo E, Barreiro P, et al. Hepatitis delta is a major determinant of liver decompensation events and death in HIV-infected patients. Clin Infect Dis. 2014;58(11):1549–53.

    PubMed  Google Scholar 

  86. Sheng WH, Hung CC, Kao JH, Chang SY, Chen MY, Hsieh SM, et al. Impact of hepatitis D virus infection on the long-term outcomes of patients with hepatitis B virus and HIV coinfection in the era of highly active antiretroviral therapy: a matched cohort study. Clin Infect Dis. 2007;44(7):988–95.

    PubMed  Google Scholar 

  87. Hsieh MH, Wang SC, Hsieh MY, Huang CF, Yeh ML, Yang JF, et al. Hepatitis D virus infections among injecting drug users with and without human immunodeficiency virus infection in Taiwan. Kaohsiung J Med Sci. 2016;32(10):526–30.

    PubMed  Google Scholar 

  88. Chang SY, Yang CL, Ko WS, Liu WC, Lin CY, Wu CH, et al. Molecular epidemiology of hepatitis D virus infection among injecting drug users with and without human immunodeficiency virus infection in Taiwan. J Clin Microbiol. 2011;49(3):1083–9.

    PubMed  PubMed Central  Google Scholar 

  89. Coffie PA, Tchounga BK, Bado G, Kabran M, Minta DK, Wandeler G, et al. Prevalence of hepatitis B and delta according to HIV-type: a multi-country cross-sectional survey in West Africa. BMC Infect Dis. 2017;17(1):466.

    PubMed  PubMed Central  Google Scholar 

  90. Katwesigye E, Seremba E, Semitala F, Ocama P. Low sero-prevalence of hepatitis delta antibodies in HIV/ hepatitis B co-infected patients attending an urban HIV clinic in Uganda. Afr Health Sci. 2016;16(4):1089–93.

    PubMed  PubMed Central  Google Scholar 

  91. Lee CY, Tsai HC, Lee SS, et al. Higher rate of hepatitis events in patients with human immunodeficiency virus, hepatitis B, and hepatitis D genotype II infection: a cohort study in a medical center in southern Taiwan. J Microbiol Immunol Infect. 2015;48(1):20–7.

    PubMed  Google Scholar 

  92. Hung CC, Wu SM, Lin PH, Sheng WH, Yang ZY, Sun HY, et al. Increasing incidence of recent hepatitis D virus infection in HIV-infected patients in an area hyperendemic for hepatitis B virus infection. Clin Infect Dis. 2014;58(11):1625–33.

    CAS  PubMed  PubMed Central  Google Scholar 

  93. Thio CL, Smeaton L, Saulynas M, Hwang H, Saravan S, Kulkarni S, et al. Characterization of HIV-HBV coinfection in a multinational HIV-infected cohort. AIDS. 2013;27(2):191–201.

    CAS  PubMed  PubMed Central  Google Scholar 

  94. Mendes-Correa MC, Gomes-Gouvêa MS, Alvarado-Mora MV, da Silva MH, Lázari C, Cavalcanti NCS, et al. Hepatitis delta in HIV/HBV co-infected patients in Brazil: is it important? Int J Infect Dis. 2011;15(12):e828–32.

    PubMed  Google Scholar 

  95. Thio CL, Seaberg EC, Skolasky R, et al. HIV-1, hepatitis B virus, and risk of liver-related mortality in the Multicenter Cohort Study (MACS). Lancet. 2002;360(9349):1921–6.

    PubMed  Google Scholar 

  96. •• Saag MS, Benson CA, Gandhi RT, et al. Antiretroviral drugs for treatment and prevention of HIV infection in adults: 2018 recommendations of the International Antiviral Society-USA Panel. JAMA. 2018;320(4):379–96. These are the most recent guidelines for the treatment of HIV infection.

    CAS  PubMed  PubMed Central  Google Scholar 

  97. Delaney WE, Ray AS, Yang H, et al. Intracellular metabolism and in vitro activity of tenofovir against hepatitis B virus. Antimicrob Agents Chemother. 2006;50(7):2471–7.

    CAS  PubMed  PubMed Central  Google Scholar 

  98. Heathcote EJ, Marcellin P, Buti M, Gane E, de Man RA, Krastev Z, et al. Three-year efficacy and safety of tenofovir disoproxil fumarate treatment for chronic hepatitis B. Gastroenterology. 2011;140(1):132–43.

    CAS  PubMed  Google Scholar 

  99. Marcellin P, Gane E, Buti M, Afdhal N, Sievert W, Jacobson IM, et al. Regression of cirrhosis during treatment with tenofovir disoproxil fumarate for chronic hepatitis B: a 5-year open-label follow-up study. Lancet. 2013;381(9865):468–75.

    CAS  PubMed  Google Scholar 

  100. Snow-Lampart A, Chappell B, Curtis M, Zhu Y, Myrick F, Schawalder J, et al. No resistance to tenofovir disoproxil fumarate detected after up to 144 weeks of therapy in patients monoinfected with chronic hepatitis B virus. Hepatology. 2011;53(3):763–73.

    CAS  PubMed  Google Scholar 

  101. Gordon SC, Krastev Z, Horban A, Petersen J, Sperl J, Dinh P, et al. Efficacy of tenofovir disoproxil fumarate at 240 weeks in patients with chronic hepatitis B with high baseline viral load. Hepatology. 2013;58(2):505–13.

    CAS  PubMed  PubMed Central  Google Scholar 

  102. Sheldon J, Camino N, Rodes B, et al. Selection of hepatitis B virus polymerase mutations in HIV-coinfected patients treated with tenofovir. Antivir Ther. 2005;10(6):727–34.

    CAS  PubMed  Google Scholar 

  103. De Vries-Sluijs TE, Reijnders JG, Hansen BE, et al. Long-term therapy with tenofovir is effective for patients co-infected with human immunodeficiency virus and hepatitis B virus. Gastroenterology. 2010;139(6):1934–41.

    PubMed  Google Scholar 

  104. Lada O, Gervais A, Branger M, Peytavin G, Roquebert B, Collin G, et al. Long-term outcome of primary non-responders to tenofovir therapy in HIV/HBV-co-infected patients: impact of HBV genotype G. Liver Int. 2012;32(1):93–101.

    CAS  PubMed  Google Scholar 

  105. Gunthard HF, Aberg JA, Eron JJ, et al. Antiretroviral treatment of adult HIV infection: 2014 recommendations of the International Antiviral Society-USA Panel. JAMA. 2014;312(4):410–25.

    PubMed  Google Scholar 

  106. McMahon MA, Jilek BL, Brennan TP, et al. The HBV drug entecavir - effects on HIV-1 replication and resistance. N Engl J Med. 2007;356(25):2614–21.

    CAS  PubMed  PubMed Central  Google Scholar 

  107. Matthews GV, Bartholomeusz A, Locarnini S, Ayres A, Sasaduesz J, Seaberg E, et al. Characteristics of drug resistant HBV in an international collaborative study of HIV-HBV-infected individuals on extended lamivudine therapy. AIDS. 2006;20(6):863–70.

    CAS  PubMed  Google Scholar 

  108. Kim HN, Rodriguez CV, Van Rompaey S, et al. Factors associated with delayed hepatitis B viral suppression on tenofovir among patients coinfected with HBV-HIV in the CNICS cohort. J Acquir Immune Defic Syndr. 2014;66(1):96–101.

    CAS  PubMed  PubMed Central  Google Scholar 

  109. Lok AS, McMahon BJ. Chronic hepatitis B. Hepatology. 2007;45(2):507–39.

    CAS  PubMed  Google Scholar 

  110. Lai CL, Yuen MF. The natural history and treatment of chronic hepatitis B: a critical evaluation of standard treatment criteria and end points. Ann Intern Med. 2007;147(1):58–61.

    PubMed  Google Scholar 

  111. Liaw YF, Leung N, Kao JH, Piratvisuth T, Gane E, Han KH, et al. Asian-Pacific consensus statement on the management of chronic hepatitis B: a 2008 update. Hepatol Int. 2008;2(3):263–83.

    PubMed  PubMed Central  Google Scholar 

  112. Soriano V, Puoti M, Peters M, Benhamou Y, Sulkowski M, Zoulim F, et al. Care of HIV patients with chronic hepatitis B: updated recommendations from the HIV-Hepatitis B Virus International Panel. AIDS. 2008;22(12):1399–410.

    PubMed  Google Scholar 

  113. •• Cornberg M, Lok AS, Terrault NA, Zoulim F, Faculty E-AHTEC. Guidance for design and endpoints of clinical trials in chronic hepatitis B - Report from the 2019 EASL-AASLD HBV Treatment Endpoints Conference. J Hepatol. 2019. Available from: https://doi.org/10.1002/hep.31030. Recommendations for treatment endpoints for HBV and HDV therapies in clinical trials.

  114. Dore GJ, 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(6):857–65.

    PubMed  PubMed Central  Google Scholar 

  115. 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(3):227–32.

    CAS  PubMed  Google Scholar 

  116. Lau DT, Doo E, Park Y, Kleiner DE, Schmid P, Kuhns MC, et al. Lamivudine for chronic delta hepatitis. Hepatology. 1999;30(2):546–9.

    CAS  PubMed  Google Scholar 

  117. Soriano V, Vispo E, Sierra-Enguita R, Mendoza C, Fernández-Montero JV, Labarga P, et al. Efficacy of prolonged tenofovir therapy on hepatitis delta in HIV-infected patients. AIDS. 2014;28(16):2389–94.

    CAS  PubMed  Google Scholar 

  118. Boyd A, Miailhes P, Brichler S, Scholtès C, Maylin S, Delaugerre C, et al. Effect of tenofovir with and without interferon on hepatitis D virus replication in HIV-hepatitis B virus-hepatitis D virus-infected patients. AIDS Res Hum Retrovir. 2013;29(12):1535–40.

    CAS  PubMed  Google Scholar 

  119. • Beguelin CFN, Moradpour D, et al. Impact of tenofovir on hepatitis delta virus replication in the Swiss Human Immunodeficiency Virus cohort study. Clin Infect Dis. 2017;64(9):1275–8. This cohort study found that tenofovir-containing antiretroviral therapy did not result in significant reductions in HDV RNA among HIV/HBV-coinfected patients in the Swiss HIV Cohort Study.

    PubMed  Google Scholar 

  120. Abbas Z, Khan MA, Salih M, Jafri W. Interferon alpha for chronic hepatitis D. Cochrane Database Syst Rev. 2011;12:CD006002.

    Google Scholar 

  121. Abbas Z, Memon MS, Mithani H, Jafri W, Hamid S. Treatment of chronic hepatitis D patients with pegylated interferon: a real-world experience. Antivir Ther. 2014;19(5):463–8.

    CAS  PubMed  Google Scholar 

  122. Erhardt A, Gerlich W, Starke C, Wend U, Donner A, Sagir A, et al. Treatment of chronic hepatitis delta with pegylated interferon-alpha2b. Liver Int. 2006;26(7):805–10.

    CAS  PubMed  Google Scholar 

  123. Gripon P, Cannie I, Urban S. Efficient inhibition of hepatitis B virus infection by acylated peptides derived from the large viral surface protein. J Virol. 2005;79(3):1613–22.

    CAS  PubMed  PubMed Central  Google Scholar 

  124. Slijepcevic D, Kaufman C, Wichers CG, et al. Impaired uptake of conjugated bile acids and hepatitis b virus pres1-binding in na(+) -taurocholate cotransporting polypeptide knockout mice. Hepatology. 2015;62(1):207–19.

    CAS  PubMed  PubMed Central  Google Scholar 

  125. Bogomolov P, Alexandrov A, Voronkova N, Macievich M, Kokina K, Petrachenkova M, et al. Treatment of chronic hepatitis D with the entry inhibitor myrcludex B: first results of a phase Ib/IIa study. J Hepatol. 2016;65(3):490–8.

    CAS  PubMed  Google Scholar 

  126. Al-Mahtab M, Bazinet M, Vaillant A. Safety and efficacy of nucleic acid polymers in monotherapy and combined with immunotherapy in treatment-naive Bangladeshi patients with HBeAg+ chronic hepatitis B infection. PLoS One. 2016;11(6):e0156667.

    PubMed  PubMed Central  Google Scholar 

  127. •• Bazinet M, Pântea V, Cebotarescu V, et al. Safety and efficacy of REP 2139 and pegylated interferon alfa-2a for treatment-naive patients with chronic hepatitis B virus and hepatitis D virus co-infection (REP 301 and REP 301-LTF): a non-randomised, open-label, phase 2 trial. Lancet Gastroenterol Hepatol. 2017;2(12):877–89. This Phase 2 study found that the combination of REP 2139 and pegylated interferon alfa-2a resulted in reductions in both HDV RNA and HBsAg.

    PubMed  Google Scholar 

  128. •• Etzion OHS, Lurie Y, Gane E, Bader N, Yardeni D, Nevo-Shor A, et al. End of study results from LIMT HDV study: 36% durable virologic response at 24 weeks post-treatment with pegylated interferon lambda monotherapy in patients with chronic hepatitis delta infection. J Hepatol. 2019:E32. This Phase 2 study found that pegylated interferon lambda resulted in virologic response in 36% at 24 weeks after therapy and with improved tolerability as compared to PEG-IFN-α.

Download references

Author information

Authors and Affiliations

  1. Division of Gastroenterology and Hepatology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA

    Nicole D. Ferrante

  2. Department of Biostatistics, Epidemiology, and Informatics, Center for Clinical Epidemiology and Biostatistics, Center for Pharmacoepidemiology Research and Training, Perelman School of Medicine, University of Pennsylvania, 836 Blockley Hall, 423 Guardian Drive, Philadelphia, PA, 19104-6021, USA

    Nicole D. Ferrante & Vincent Lo Re III

  3. Division of Infectious Diseases, Department of Medicine, Perelman School of Medicine University of Pennsylvania, Philadelphia, PA, USA

    Vincent Lo Re III

  4. Center for AIDS Research, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA

    Vincent Lo Re III

Authors
  1. Nicole D. Ferrante
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Vincent Lo Re III
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Vincent Lo Re III.

Ethics declarations

Conflict of Interest

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

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

This article is part of the Topical Collection on Co-infections and Comorbidity

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Ferrante, N.D., Lo Re, V. Epidemiology, Natural History, and Treatment of Hepatitis Delta Virus Infection in HIV/Hepatitis B Virus Coinfection. Curr HIV/AIDS Rep 17, 405–414 (2020). https://doi.org/10.1007/s11904-020-00508-z

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11904-020-00508-z

Keywords

Search

Navigation