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Current Management of HBV/HDV Coinfection and Future Perspectives

  • Hepatitis B (J Lim, Section Editor)
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Abstract

The hepatitis delta virus (HDV) is the smallest virus known to infect humans. It depends on the helper function of the hepatitis B surface antigen (HBsAg), and HDV infection is therefore only possible in patients infected with hepatitis B. Worldwide, an estimated 10–20 million individuals are coinfected with HDV. Migration of patients from highly prevalent areas accounts for the majority of hepatitis delta cases in Europe and North America. Chronic hepatitis delta is the most severe form of viral hepatitis with accelerated fibrosis progression, more frequent development of liver cirrhosis, earlier hepatic decompensation, and reduced survival rates compared to HBV monoinfection. Currently, only pegylated interferon alfa can be used to treat HDV, leading to HDV RNA suppression in 25–47 % of cases. However, interferon alfa rarely induced cure of HDV infection as long-term relapses have been described in many patients. Currently, alternative treatment options like prenylation inhibitors and HBV entry inhibitors are tested in early clinical trials. Moreover, other novel compounds aiming to achieve serological cure of HBV infection would be of particular importance for hepatitis delta as HBsAg elimination would be the ultimate goal also for hepatitis delta. In this review, we summarize the current state of the art on the management of HDV infection and highlight some perspectives for novel therapies.

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References

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

  1. Cross TJ, Rizzi P, Horner M, Jolly A, Hussain MJ, Smith HM, et al. The increasing prevalence of hepatitis delta virus (HDV) infection in south London. J Med Virol. 2008;80(2):277–82.

    Article  PubMed  Google Scholar 

  2. 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. An interesting study showing that HDV infection is a rapidly progressive disease and that interferon-based treatment may alter its course.

    Article  PubMed  Google Scholar 

  3. Rizzetto M. The delta agent. Hepatology. 1983;3(5):729–37.

    Article  CAS  PubMed  Google Scholar 

  4. Taylor JM. Virology of hepatitis D virus. Semin Liver Dis. 2012;32(3):195–200.

    Article  CAS  PubMed  Google Scholar 

  5. Deny P. Hepatitis delta virus genetic variability: from genotypes I, II, III to eight major clades? Curr Top Microbiol Immunol. 2006;307:151–71.

    CAS  PubMed  Google Scholar 

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

    Article  PubMed  Google Scholar 

  7. Radjef N, Gordien E, Ivaniushina V, Gault E, Anais P, Drugan T, et al. Molecular phylogenetic analyses indicate a wide and ancient radiation of African hepatitis delta virus, suggesting a deltavirus genus of at least seven major clades. J Virol. 2004;78(5):2537–44.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

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

    Article  PubMed  Google Scholar 

  9. Schweitzer A, Horn J, Mikolajczyk RT, Krause G, Ott JJ. Estimations of worldwide prevalence of chronic hepatitis B virus infection: a systematic review of data published between 1965 and 2013. Lancet. 2015.

  10. Han M, Littlejohn M, Yuen L, Edwards R, Devi U, Bowden S, et al. Molecular epidemiology of hepatitis delta virus in the Western Pacific region. J Clin Virol. 2014;61(1):34–9.

    Article  PubMed  Google Scholar 

  11. Braga WS, de Oliveira CM, de Araujo JR, Castilho Mda C, Rocha JM, Gimaque JB, et al. Chronic HDV/HBV co-infection: predictors of disease stage—a case series of HDV-3 patients. J Hepatol. 2014;61(6):1205–11. One of the earliest reports of HDV genotype 3 confirming the severity of HDV infection in that genotype.

    Article  PubMed  Google Scholar 

  12. Kay A, Melo da Silva E, Pedreira H, Negreiros S, Lobato C, Braga W, et al. HBV/HDV co-infection in the Western Brazilian Amazonia: an intriguing mutation among HDV genotype 3 carriers. J Viral Hepat. 2014;21(12):921–4.

    Article  CAS  PubMed  Google Scholar 

  13. Tsatsralt-Od B, Takahashi M, Nishizawa T, Endo K, Inoue J, Okamoto H. High prevalence of dual or triple infection of hepatitis B, C, and delta viruses among patients with chronic liver disease in Mongolia. J Med Virol. 2005;77(4):491–9.

    Article  CAS  PubMed  Google Scholar 

  14. Abbas Z. Hepatitis D, in Pakistan. J Coll Physicians Surg Pak. 2012;22(9):547–8.

    PubMed  Google Scholar 

  15. Andernach IE, Leiss LV, Tarnagda ZS, Tahita MC, Otegbayo JA, Forbi JC, et al. Characterization of hepatitis delta virus in sub-Saharan Africa. J Clin Microbiol. 2014;52(5):1629–36.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  16. 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.

    Article  PubMed Central  PubMed  Google Scholar 

  17. Farci P, Niro GA. Clinical features of hepatitis D. Semin Liver Dis. 2012;32(3):228–36.

    Article  PubMed  Google Scholar 

  18. Gaeta GB, Stroffolini T, Chiaramonte M, Ascione T, Stornaiuolo G, Lobello S, et al. Chronic hepatitis D: a vanishing disease? An Italian multicenter study. Hepatology. 2000;32(4 Pt 1):824–7.

    Article  CAS  PubMed  Google Scholar 

  19. Degertekin H, Yalcin K, Yakut M, Yurdaydin C. Seropositivity for delta hepatitis in patients with chronic hepatitis B and liver cirrhosis in Turkey: a meta-analysis. Liver Int. 2008;28(4):494–8.

    Article  PubMed  Google Scholar 

  20. Wedemeyer H, Heidrich B, Manns MP. Hepatitis D virus infection—not a vanishing disease in Europe! Hepatology. 2007;45(5):1331–2. author reply 1332–3.

    Article  PubMed  Google Scholar 

  21. Le Gal F. C. Castelneau ea. Hepatitis D virus infection—not a vanishing disease in Europe! Reply. Hepatology. 2007;45(5):1332–3.

    Article  Google Scholar 

  22. 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(12):883–94.

    Article  CAS  PubMed  Google Scholar 

  23. Erhardt A, Knuth R, Sagir A, Kirschberg O, Heintges T, Haussinger 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.

    Article  CAS  PubMed  Google Scholar 

  24. Erhardt A, Hoernke M, Heinzel-Pleines U, Sagir A, Gobel T, Haussinger D. Retrospective analysis of chronic hepatitis D in a West German University Clinic over two decades: migratory pattern, prevalence and clinical outcome. Z Gastroenterol. 2010;48(8):813–7.

    Article  CAS  PubMed  Google Scholar 

  25. 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.

    Article  PubMed Central  PubMed  Google Scholar 

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

    Article  PubMed  Google Scholar 

  27. Ippolito AM, Niro GA, Fontana R, Lotti G, Gioffreda D, Valvano MR, et al. Unawareness of HBV infection among inpatients in a Southern Italian hospital. J Viral Hepat. 2011;18(7):e206–11.

    Article  CAS  PubMed  Google Scholar 

  28. Flodgren E, Bengtsson S, Knutsson M, Strebkova EA, Kidd AH, Alexeyev OA, et al. Recent high incidence of fulminant hepatitis in Samara, Russia: molecular analysis of prevailing hepatitis B and D virus strains. J Clin Microbiol. 2000;38(9):3311–6.

    PubMed Central  CAS  PubMed  Google Scholar 

  29. Buti M, Homs M, Rodriguez-Frias F, Funalleras G, Jardi 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.

    Article  CAS  PubMed  Google Scholar 

  30. Niro GA, Smedile A, Ippolito AM, Ciancio A, Fontana R, Olivero A, et al. Outcome of chronic delta hepatitis in Italy: a long-term cohort study. J Hepatol. 2010;53(5):834–40.

    Article  PubMed  Google Scholar 

  31. Romeo R, Del Ninno E, Rumi M, Russo A, Sangiovanni A, de Franchis R, 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.

    Article  PubMed  Google Scholar 

  32. Su CW, Huang YH, Huo TI, Shih HH, Sheen IJ, Chen SW, 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.

    Article  CAS  PubMed  Google Scholar 

  33. Romeo R, Foglieni B, Casazza G, Spreafico M, Colombo M, Prati D. High serum levels of HDV RNA are predictors of cirrhosis and liver cancer in patients with chronic hepatitis delta. PLoS One. 2014;9(3), e92062. An interesting study predicting HDV RNA levels as marker of cirrhosis and liver cancer.

    Article  PubMed Central  PubMed  Google Scholar 

  34. Calle Serrano B, Grosshennig A, Homs M, Heidrich B, Erhardt A, Deterding K, et al. Development and evaluation of a baseline-event-anticipation score for hepatitis delta. J Viral Hepat. 2014;21(11):e154–63. One interesting study building a score which identified patients under risk of developing liver-related complications.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  35. Fernandez-Montero JV, Vispo E, Barreiro P, Sierra-Enguita R, de Mendoza C, Labarga 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. Important study indicating high rates of death and liver decompensation in patients infected with hepatitis delta and HIV.

    Article  CAS  PubMed  Google Scholar 

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

    Article  PubMed  Google Scholar 

  37. Huang YH, Tao MH, Hu CP, Syu WJ, Wu JC. Identification of novel HLA-A*0201-restricted CD8+ T-cell epitopes on hepatitis delta virus. J Gen Virol. 2004;85(Pt 10):3089–98.

    Article  CAS  PubMed  Google Scholar 

  38. Aslan N, Yurdaydin C, Wiegand J, Greten T, Ciner A, Meyer MF, et al. Cytotoxic CD4 T cells in viral hepatitis. J Viral Hepat. 2006;13(8):505–14.

    Article  CAS  PubMed  Google Scholar 

  39. Lunemann S, Malone DF, Hengst J, Port K, Grabowski J, Deterding K, et al. Compromised function of natural killer cells in acute and chronic viral hepatitis. J Infect Dis. 2014;209(9):1362–73. This study suggested that disease activity is dependent on alteration of NK cell phenotype and function.

    Article  CAS  PubMed  Google Scholar 

  40. Lunemann S, Malone DF, Grabowski J, Port K, Beziat V, Bremer B, et al. Effects of HDV infection and pegylated interferon alpha treatment on the natural killer cell compartment in chronically infected individuals. Gut. 2015;64(3):469–82. A detailed study describing how HDV infection and IFN-α treatment affect the NK cell compartment and what consequences this has for the functional capacity of NK cells.

    Article  CAS  PubMed  Google Scholar 

  41. Grabowski J, Yurdaydin C, Zachou K, Buggisch P, Hofmann WP, Jaroszewicz J, et al. Hepatitis D virus-specific cytokine responses in patients with chronic hepatitis delta before and during interferon alfa-treatment. Liver Int. 2011;31(9):1395–405.

    Article  CAS  PubMed  Google Scholar 

  42. 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. This study underlines the predictive character of anti-HDV IgM as a marker of disease activity.

    Article  PubMed Central  PubMed  Google Scholar 

  43. 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.

    Article  CAS  PubMed  Google Scholar 

  44. 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.

    Article  CAS  PubMed  Google Scholar 

  45. Wedemeyer H. Re-emerging interest in hepatitis delta: new insights into the dynamic interplay between HBV and HDV. J Hepatol. 2010;52(5):627–9.

    Article  PubMed  Google Scholar 

  46. 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.

    Article  PubMed  Google Scholar 

  47. Heidrich B, Serrano BC, Idilman R, Kabacam G, Bremer B, Raupach R, et al. HBeAg-positive hepatitis delta: virological patterns and clinical long-term outcome. Liver Int. 2012;32(9):1415–25. The first analysis distinguishing the clinical long-term outcome due to HBeAg status in patients infected with hepatitis delta.

    Article  CAS  PubMed  Google Scholar 

  48. Williams V, Brichler S, Radjef N, Lebon P, Goffard A, Hober D, et al. Hepatitis delta virus proteins repress hepatitis B virus enhancers and activate the alpha/beta interferon-inducible MxA gene. J Gen Virol. 2009;90(Pt 11):2759–67.

    Article  CAS  PubMed  Google Scholar 

  49. Deterding K, Pothakamuri SV, Schlaphoff V, Hadem J, Metzler F, Bahr MJ, et al. Clearance of chronic HCV infection during acute delta hepatitis. Infection. 2009;37(2):159–62.

    Article  CAS  PubMed  Google Scholar 

  50. Benegiamo G, Vinciguerra M, Guarnieri V, Niro GA, Andriulli A, Pazienza V. Hepatitis delta virus induces specific DNA methylation processes in Huh-7 liver cancer cells. FEBS Lett. 2013;587(9):1424–8.

    Article  CAS  PubMed  Google Scholar 

  51. Mederacke I, Yurdaydin C, Dalekos GN, Bremer B, Erhardt A, Cakaloglu Y, et al. Anti-HDV immunoglobulin M testing in hepatitis delta revisited: correlations with disease activity and response to pegylated interferon-alpha2a treatment. Antivir Ther. 2012;17(2):305–12.

    Article  CAS  PubMed  Google Scholar 

  52. Mederacke I, Bremer B, Heidrich B, Kirschner J, Deterding K, Bock T, 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(6):2022–9. One of several important reports that established the so far earliest novel automated HDV RNA assay.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  53. Brichler S, Le Gal F, Butt A, Chevret S, Gordien E. Commercial real-time reverse transcriptase PCR assays can underestimate or fail to quantify hepatitis delta virus viremia. Clin Gastroenterol Hepatol. 2013;11(6):734–40. Large analysis which revealed controversial quantification results of HDV RNA in African patients infected with strains of genotypes 1 and 5 to 8.

    Article  CAS  PubMed  Google Scholar 

  54. 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 

  55. Katsoulidou A, Manesis E, Rokka C, Issaris C, Pagoni A, Sypsa V, et al. Development and assessment of a novel real-time PCR assay for quantitation of hepatitis D virus RNA to study viral kinetics in chronic hepatitis D. J Viral Hepat. 2013;20(4):256–62.

    Article  CAS  PubMed  Google Scholar 

  56. Botelho-Souza LF, dos Santos AO, Borzacov LM, Honda ER, Villalobos-Salcedo JM, Vieira DS. Development of a reverse transcription quantitative real-time PCR-based system for rapid detection and quantitation of hepatitis delta virus in the western Amazon region of Brazil. J Virol Methods. 2014;197:19–24.

    Article  CAS  PubMed  Google Scholar 

  57. Rizzetto M, Rosina F, Saracco G, Bellando PC, Actis GC, Bonino F, et al. Treatment of chronic delta hepatitis with alpha-2 recombinant interferon. J Hepatol. 1986;3 Suppl 2:S229–33.

    Article  PubMed  Google Scholar 

  58. Farci P, Mandas A, Coiana A, Lai ME, Desmet V, Van Eyken P, et al. Treatment of chronic hepatitis D with interferon alfa-2a. N Engl J Med. 1994;330(2):88–94.

    Article  CAS  PubMed  Google Scholar 

  59. Farci P, Roskams T, Chessa L, Peddis G, Mazzoleni AP, Scioscia R, et al. Long-term benefit of interferon alpha therapy of chronic hepatitis D: regression of advanced hepatic fibrosis. Gastroenterology. 2004;126(7):1740–9.

    Article  CAS  PubMed  Google Scholar 

  60. Gunsar F, Akarca US, Ersoz G, Kobak AC, Karasu Z, Yuce G, et al. Two-year interferon therapy with or without ribavirin in chronic delta hepatitis. Antivir Ther. 2005;10(6):721–6.

    CAS  PubMed  Google Scholar 

  61. Niro GA, Ciancio A, Tillman HL, Lagget M, Olivero A, Perri F, et al. Lamivudine therapy in chronic delta hepatitis: a multicentre randomized-controlled pilot study. Aliment Pharmacol Ther. 2005;22(3):227–32.

    Article  CAS  PubMed  Google Scholar 

  62. Lau DT, Kleiner DE, Park Y, Di Bisceglie AM, Hoofnagle JH. Resolution of chronic delta hepatitis after 12 years of interferon alfa therapy. Gastroenterology. 1999;117(5):1229–33.

    Article  CAS  PubMed  Google Scholar 

  63. Niro GA, Rosina F, Rizzetto M. Treatment of hepatitis D. J Viral Hepat. 2005;12(1):2–9.

    Article  CAS  PubMed  Google Scholar 

  64. Castelnau C, Le Gal F, Ripault MP, Gordien E, Martinot-Peignoux M, Boyer N, et al. Efficacy of peginterferon alpha-2b in chronic hepatitis delta: relevance of quantitative RT-PCR for follow-up. Hepatology. 2006;44(3):728–35.

    Article  CAS  PubMed  Google Scholar 

  65. Niro GA, Ciancio A, Gaeta GB, Smedile A, Marrone A, Olivero A, et al. Pegylated interferon alpha-2b as monotherapy or in combination with ribavirin in chronic hepatitis delta. Hepatology. 2006;44(3):713–20.

    Article  CAS  PubMed  Google Scholar 

  66. 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.

    Article  CAS  PubMed  Google Scholar 

  67. Wedemeyer H, Yurdaydin C, Dalekos GN, Erhardt A, Cakaloglu Y, Degertekin H, et al. Peginterferon plus adefovir versus either drug alone for hepatitis delta. N Engl J Med. 2011;364(4):322–31. The so far largest study investigating the effect of interferon-based therapy in patients infected with hepatitis delta.

    Article  CAS  PubMed  Google Scholar 

  68. Ormeci N, Bolukbas F, Erden E, Coban S, Ekiz F, Erdem H, et al. Pegylated interferon alfa-2B for chronic delta hepatitis: 12 versus 24 months. Hepato-Gastroenterology. 2011;58(110–111):1648–53.

    CAS  PubMed  Google Scholar 

  69. Karaca C, Soyer OM, Baran B, Ormeci AC, Gokturk S, Aydin E, et al. Efficacy of pegylated interferon-alpha treatment for 24 months in chronic delta hepatitis and predictors of response. Antivir Ther. 2013;18(4):561–6.

    Article  CAS  PubMed  Google Scholar 

  70. 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.

    Article  CAS  PubMed  Google Scholar 

  71. Heller T, Rotman Y, Koh C, Clark S, Haynes-Williams V, Chang R, et al. Long-term therapy of chronic delta hepatitis with peginterferon alfa. Aliment Pharmacol Ther. 2014;40(1):93–104.

    Article  CAS  PubMed  Google Scholar 

  72. Heidrich B, Yurdaydin C, Kabacam G, Ratsch BA, Zachou K, Bremer B, et al. Late HDV RNA relapse after peginterferon alpha-based therapy of chronic hepatitis delta. Hepatology. 2014;60(1):87–97. One important study demonstrating that late HDV RNA relapses may occur after PEG-IFN-α therapy and that therefore the term sustained virological response should be avoided in HDV infection. Nevertheless, patients responding to therapy showed lower rates of clinical events.

    Article  CAS  PubMed  Google Scholar 

  73. Wedemeyer H, Yurdaydın C, Caruntu FA, Curescu MG, Yalçın K, Akarca US, et al. Pegylated-interferon-alfa-2a plus tenofovir or placebo for the treatment of hepatitis delta. London: 49th Annual Meeting of the European Association for the Study of the Liver (EASL 2014); 2014. The most recent multicentric study of patients treated with PEG-IFN-α monotherapy or in combination with tenofovir.

    Google Scholar 

  74. Keskin O, Wedemeyer H, Tuzun A, Zachou K, Deda X, Dalekos GN, et al. Association between level of hepatitis D virus RNA at week 24 of pegylated interferon therapy and outcome. Clin Gastroenterol Hepatol. 2015. One of several important analyses which identified HDV RNA levels at week 24 of treatment with PEG-IFN as a predictive marker of treatment response.

  75. Yilmaz E, Baran B, Soyer OM, Onel M, Onel D, Ormeci AC, et al. Effects of polymorphisms in interferon lambda 3 (interleukin 28B) on sustained virologic response to therapy in patients with chronic hepatitis D virus infection. Clin Gastroenterol Hepatol. 2014;12(10):1753–8.

    Article  CAS  PubMed  Google Scholar 

  76. Guedj J, Rotman Y, Cotler SJ, Koh C, Schmid P, Albrecht J, et al. Understanding early serum hepatitis D virus and hepatitis B surface antigen kinetics during pegylated interferon-alpha therapy via mathematical modeling. Hepatology. 2014;60(6):1902–10.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  77. Wolters LM, van Nunen AB, Honkoop P, Vossen AC, Niesters HG, Zondervan PE, et al. Lamivudine-high dose interferon combination therapy for chronic hepatitis B patients co-infected with the hepatitis D virus. J Viral Hepat. 2000;7(6):428–34.

    Article  CAS  PubMed  Google Scholar 

  78. 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.

    Article  CAS  PubMed  Google Scholar 

  79. Yurdaydin C, Bozkaya H, Onder FO, Senturk H, Karaaslan H, Akdogan M, et al. Treatment of chronic delta hepatitis with lamivudine vs lamivudine + interferon vs interferon. J Viral Hepat. 2008;15(4):314–21.

    Article  CAS  PubMed  Google Scholar 

  80. Yurdaydin C, Bozkaya H, Gurel S, Tillmann HL, Aslan N, Okcu-Heper A, et al. Famciclovir treatment of chronic delta hepatitis. J Hepatol. 2002;37(2):266–71.

    Article  CAS  PubMed  Google Scholar 

  81. Garripoli A, Di Marco V, Cozzolongo R, Costa C, Smedile A, Fabiano A, et al. Ribavirin treatment for chronic hepatitis D: a pilot study. Liver. 1994;14(3):154–7.

    Article  CAS  PubMed  Google Scholar 

  82. Kabacam G, Onder FO, Yakut M, Seven G, Karatayli SC, Karatayli E, et al. Entecavir treatment of chronic hepatitis D. Clin Infect Dis. 2012;55(5):645–50.

    Article  CAS  PubMed  Google Scholar 

  83. Calle Serrano B, Manns MP, Wedemeyer H. Hepatitis delta and HIV infection. Semin Liver Dis. 2012;32(2):120–9.

    Article  PubMed  Google Scholar 

  84. Sheldon J, Ramos B, Toro C, Rios P, Martinez-Alarcon J, Bottecchia M, et al. Does treatment of hepatitis B virus (HBV) infection reduce hepatitis delta virus (HDV) replication in HIV-HBV-HDV-coinfected patients? Antivir Ther. 2008;13(1):97–102.

    CAS  PubMed  Google Scholar 

  85. Soriano V, Vispo E, Sierra-Enguita R, Mendoza C, Fernandez-Montero JV, Labarga P, et al. Efficacy of prolonged tenofovir therapy on hepatitis delta in HIV-infected patients. AIDS. 2014;28(16):2389–94. Long-term analysis of patients infected with hepatitis delta and HIV who were treated with tenofovir showing reduced HDV RNA levels.

    Article  CAS  PubMed  Google Scholar 

  86. Rosenau J, Kreutz T, Kujawa M, Bahr MJ, Rifai K, Hooman N, et al. HBsAg level at time of liver transplantation determines HBsAg decrease and anti-HBs increase and affects HBV DNA decrease during early immunoglobulin administration. J Hepatol. 2007;46(4):635–44.

    Article  CAS  PubMed  Google Scholar 

  87. Smedile A, Casey JL, Cote PJ, Durazzo M, Lavezzo B, Purcell RH, et al. Hepatitis D viremia following orthotopic liver transplantation involves a typical HDV virion with a hepatitis B surface antigen envelope. Hepatology. 1998;27(6):1723–9.

    Article  CAS  PubMed  Google Scholar 

  88. Mederacke I, Filmann N, Yurdaydin C, Bremer B, Puls F, Zacher BJ, et al. Rapid early HDV RNA decline in the peripheral blood but prolonged intrahepatic hepatitis delta antigen persistence after liver transplantation. J Hepatol. 2012;56(1):115–22.

    Article  CAS  PubMed  Google Scholar 

  89. Giersch K, Helbig M, Volz T, Allweiss L, Mancke LV, Lohse AW, et al. Persistent hepatitis D virus mono-infection in humanized mice is efficiently converted by hepatitis B virus to a productive co-infection. J Hepatol. 2014;60(3):538–44. First mouse model demonstrating that HDV can persist intrahepatically and may convert to a productive infection.

    Article  CAS  PubMed  Google Scholar 

  90. Bordier BB, Ohkanda J, Liu P, Lee SY, Salazar FH, Marion PL, et al. In vivo antiviral efficacy of prenylation inhibitors against hepatitis delta virus. J Clin Invest. 2003;112(3):407–14.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  91. 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. First 2A double-blind, randomised, placebo-controlled study assessing the effect of the prenylation inhibitor lonafarnib on patients infected with hepatitis delta.

  92. Urban S, Bartenschlager R, Kubitz R, Zoulim F. Strategies to inhibit entry of HBV and HDV into hepatocytes. Gastroenterology. 2014;147(1):48–64.

    Article  CAS  PubMed  Google Scholar 

  93. Ni Y, Lempp FA, Mehrle S, Nkongolo S, Kaufman C, Falth M, et al. Hepatitis B and D viruses exploit sodium taurocholate co-transporting polypeptide for species-specific entry into hepatocytes. Gastroenterology. 2014;146(4):1070–83. Important bioinformatic analyses of comparative expression arrays confirming that sodium-taurocholate co-transporter polypeptide is a specific receptor for HBV and HDV.

    Article  CAS  PubMed  Google Scholar 

  94. Urban S, Bogomolov P, Voronkova N, Allweiss L, Dandri M, Schwab M, et al. A proof-of-concept phase 2a clinical trial with HBV/HDV entry inhibitor Myrcludex B. Boston: 65th Annual Meeting of the American Association for the Study of Liver (AASLD 2014); 2014. One of the first studies analyzing the effect of HBV/HDV entry inhibitor Myrcludex B in patients infected with HDV.

    Google Scholar 

  95. Rizzetto M, Smedile A. Pegylated interferon therapy of chronic hepatitis D: in need of revision. Hepatology. 2015;61(4):1109–11.

    Article  CAS  PubMed  Google Scholar 

  96. Gheorghe L, Iacob S, Simionov I, Vadan R, Constantinescu I, Caruntu F, et al. Weight-based dosing regimen of peg-interferon alpha-2b for chronic hepatitis delta: a multicenter Romanian trial. J Gastrointestin Liver Dis. 2011;20(4):377–82.

    PubMed  Google Scholar 

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Correspondence to H. Wedemeyer.

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Anika Wranke declares no conflicts of interest. Heiner Wedemeyer has received honoraria for speaking or consulting from Abbott, Abbvie, BMS, Boehringer Ingelheim, BMS, Eiger, Gilead Sciences, Janssen, Merck/MSD, MyrGmbH, Novartis, Novira, Roche Diagnostics, Roche, Siemens, and Transgene.

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Wranke, A., Heidrich, B., Hardtke, S. et al. Current Management of HBV/HDV Coinfection and Future Perspectives. Curr Hepatology Rep 14, 284–292 (2015). https://doi.org/10.1007/s11901-015-0280-8

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