Viral hepatitis delta: Possibilities of therapy

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Abstract

Chronic delta hepatitis is still remaining an unresolved global health care problem. Current analytical review discusses the possibility of treating this disease with medicaments aimed at suppressing various stages of hepatitis delta virus (HDV) reproduction. The data obtained in clinical trials of new medicines and the results of their use in real clinical practice are also analyzed.

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About the authors

Olga V. Isaeva

Central Research Institute of Epidemiology of Rospotrebnadzor; I.I. Mechnikov Scientific Research Institute of Vaccines and Serums

Author for correspondence.
Email: isaeva.06@mail.ru
ORCID iD: 0000-0002-2656-3667

Doctor of Biological Sciences, Central Research Institute of Epidemiology of Rospotrebnadzor, Leading Researcher at the Laboratory of Viral Hepatites, I.I. Mechnikov Scientific Research Institute of Vaccines and Serums

Russian Federation, Moscow; Moscow

Karen K. Kyuregyan

Central Research Institute of Epidemiology of Rospotrebnadzor; I.I. Mechnikov Scientific Research Institute of Vaccines and Serums

Email: isaeva.06@mail.ru
ORCID iD: 0000-0002-3599-117X

Doctor of Biological Sciences, Professor of the Russian Academy of Sciences, Central Research Institute of Epidemiology of Rospotrebnadzor, Leading Researcher at the Laboratory of Viral Hepatites, I.I. Mechnikov Scientific Research Institute of Vaccines and Serums

Russian Federation, Moscow; Moscow

Saniyat A. Magomedova

Dagestan State Medical University of the Ministry of Healthcare of Russia

Email: isaeva.06@mail.ru
ORCID iD: 0000-0002-3512-6047

PhD in Medical Sciences, Associate Professor of the Department of the Faculty of Advanced Training and Professional Retraining of Specialists

Russian Federation, Makhachkala

Mikhail I. Mikhailov

Central Research Institute of Epidemiology of Rospotrebnadzor; I.I. Mechnikov Scientific Research Institute of Vaccines and Serums

Email: isaeva.06@mail.ru
ORCID iD: 0000-0002-6636-6801

MD, Corresponding Member of the Russian Academy of Sciences, Head of the Laboratory of Viral Hepatitis, I.I. Mechnikov Scientific Research Institute of Vaccines and Serums, Central Research Institute of Epidemiology of Rospotrebnadzor

Russian Federation, Moscow; Moscow

References

  1. Hughes S.A., H. Wedemeyer., P.M. Harrison. Hepatitis delta virus. Lancet. 2011; 378(9785): 73–85. https://dx.doi.org/10.1016/S0140-6736(10)61931-9.
  2. Lempp F.A., Nubbaum L., Rieble L. et al. Screening an FDA-approved drug library on a cell line that supports the full lifecycle of hepatitis delta virus. J Hepatol. 2016; 64; 388.
  3. Lampertico P., Agarwal K., Berg T. et al. EASL 2017 clinical practice guidelines on the management of hepatitis B virus infection. J Hepatol. 2017; 67(2): 370–98. https://dx.doi.org/10.1016/j.jhep.2017.03.021.
  4. Wranke A., Serrano B.C., Heidrich B. et al. Antiviral treatment and liver-related complications in hepatitis delta. Hepatology. 2017; 65(2) :414–25. https://dx.doi.org/10.1002/hep.28876.
  5. Yurdaydin C., Keskin O., Kalkan C. et al. Interferon treatment duration in patients with chronic delta hepatitis and its effect on the natural course of the disease. J Infect Dis. 2018; 217(8): 1184–92. https://dx.doi.org/10.1093/infdis/jix656.
  6. Cornberg M., Lok A.S.-F., Terrault N.A., Zoulim F. Guidance for design and endpoints of clinical trials in chronic hepatitis B – report from the 2019 EASL-AASLD HBV treatment endpoints conference. J Hepatol. 2020; 72(3): 539–57. https://dx.doi.org/10.1016/j.jhep.2019.11.003.
  7. Yurdaydin C., Abbas Z., Buti M. et al. Treating chronic hepatitis delta: the need for surrogate markers of treatment efficacy. J Hepatol. 2019; 70(5):1008–15. https://dx.doi.org/10.1016/j.jhep.2018.12.022.
  8. Yurdaydin C. Treatment of chronic delta hepatitis. Semin Liver Dis. 2012; 32(3): 237–44. https://dx.doi.org/10.1055/s-0032-1323629.
  9. Wranke A., Wedemeyer H. Antiviral therapies for hepatitis delta virus infection – progress ad challenges towards cure. Curr Opin Virol. 2016; 20: 112–18. https://dx.doi.org/10.1016/j.coviro.2016.10.002.
  10. Erhardt A., Gerlich W., Starke C. et al. Treatment of chronic hepatitis delta with pegylated interferon-alpha2b. Liver Int. 2006; 26(7): 805–10. https://dx.doi.org/10.1111/j.1478-3231.2006.01279.x.
  11. Karaca C., Soyer O., Baran B. Efficacy of pegylated interferon-α treatment for 24 months in chronic hepatitis delta and predictors of response. Antivir Ther. 2013; 18(4): 561–66. https://dx.doi.org/10.3851/IMP2381.
  12. Niro G., Ciancio A., Gaeta G. et al. Pegylated interferonalpha-2b as monotherapy or in combination with ribavirin in chronic hepatitis delta. Hepatology. 2006; 44(3): 713–20. https://dx.doi.org/10.1002/hep.21296.
  13. Ormeci N., Bolukbas F., Erden E. et al. Pegylated interferonalfa-2B for chronic delta hepatitis: 12 versus 24 month. Hepatogastroenterol. 2011; 58(110–111): 1648–53. https://dx.doi.org/10.5754/hge10126.
  14. Farci P., Roskams T., Chessa L. et al. Long-term benefit of interferon alpha therapy of chronic hepatitis D: Regression of advanced hepatic fibrosis. Gastroenterology. 2004; 126(7): 1740–49. https://dx.doi.org/10.1053/j.gastro.2004.03.017.
  15. Wedemeyer H., Yurdaydin C., Dalekos G. et al Pegylated interferon plus adefovir versus either drug alone for hepatitis delta. N Engl J Med. 2011; 364(4): 322–31. https://dx.doi.org/10.1056/NEJMoa0912696.
  16. Pugnale P., Pazienza V., Guilloux K., Negro F. Hepatitis delta virus inhibits alpha interferon signaling. Hepatology. 2009; 49(2): 398–406. https://dx.doi.org/10.1002/hep.22654.
  17. Giersch K., Perez-Gonzalez P., Hendricks L. et al. Strain-specific responsiveness of hepatitis D virus to interferon-alpha treatment. JHEP Rep. 2023; 5(4): 100673. https://dx.doi.org/10.1016/j.jhepr.2023.100673.
  18. Zhang Z., Filzmayer C., Ni Y. et al. Hepatitis D virus replication is sensed by MDA5 and induces IFN-β/λ responses in hepatocytes. J Hepatol. 2018; 69(1): 25–35. https://dx.doi.org/10.1016/j.jhep.2018.02.021.
  19. European Association for the Study of the Liver. EASL 2017 Clinical Practice Guidelines on the management of hepatitis B virus infection. J Hepatol. 2017; 67(2): 370–98. https://dx.doi.org/10.1016/j.jhep.2017.03.021.
  20. Brancaccio G., Fasano M., Grossi A. et al. Clinical outcomes in patients with hepatitis D, cirrhosis and persistent hepatitis B virus replication, and receiving long-term tenofovir or entecavir. Aliment Pharmacol Ther. 2019; 49(8): 1071–76. https://dx.doi.org/10.1111/apt.15188.
  21. Wedemeyer H., Yurdaydin C., Ernst S. et al Prolonged therapy of hepatitis delta for 96 weeks with pegylated interferon alfa plus tenofovir or placebo does not prevent HDV-RNA relapse after treatment: the HIDIT-2 study. J Hepatol. 2014; 60(1): S2–3. https://dx.doi.org/10.1016/S0168-8278(14)60006-4.
  22. Alvarado-Mora M.V., Romano C.M., Gomes-Gouvea M.S. et al. Dynamics of hepatitis D (delta) virus genotype 3 in the Amazon region of South America. Infect Genet Evol. 2011; 11(6): 1462–68. https://dx.doi.org/10.1016/j.meegid.2011.05.020.
  23. Lempp F.A., Ni Y., Urban S. Hepatitis delta virus: Insights into a peculiar pathogen and novel treatment options. Nat Rev Gastroenterol Hepatol. 2016; 13(10): 580–89. https://dx.doi.org/10.1038/nrgastro.2016.126.
  24. Yurdaydin C. Recent advances in managing hepatitis D. F1000Res. 2017; 6: 1596. https://dx.doi.org/10.12688/f1000research.11796.1.
  25. Hamid S.S., Etzion O., Lurie Y. et al. A phase 2 randomized clinical trial to evaluate the safety and efficacy of pegylated interferon lambda monotherapy in patients with chronic hepatitis delta virus infection. Interim results from the LIMT HDV Study (abstr.). Hepatology. 2017; 66: 496A.
  26. Abbas Z., Yakoob J., Umer M.A. et al. Interferon lambda-3 polymorphism and response to pegylated interferon in patients with hepatitis D. Antivir Ther. 2015; 20(5): 529–33. https://dx.doi.org/10.3851/IMP2943. Epub 2015 Feb 10.
  27. Wranke A., Serrano B.C., Heidrich B. et al. Antiviral treatment and liver-related complications in hepatitis delta. Hepatology. 2017; 65(2): 414–25. https://dx.doi.org/10.1002/hep.28876.
  28. Nkongolo S., Hollnberger J., Urban S. [[Bulevirtide as the first specific agent against hepatitis D virus infections-mechanism and clinical effect. Bundesgesundheitsblatt Gesundheitsforschung Gesundheitsschutz. 2022; 65(2): 254–63 (In German). https://dx.doi.org/10.1007/s00103-022-03486-2.
  29. Soriano V., Barreiro P., Sherman K.E. The changing epidemiology of liver disease in HIV patients. AIDS Rev. 2013; 15(1): 25–31.
  30. Blank A., Meier K., Urban S. et al. Drug-drug interaction potential of the HBV and HDV entry inhibitor myrcludex B assessed in vitro. Antivir Ther. 2018; 23(3): 267–75. https://dx.doi.org/10.3851/IMP3206.
  31. Schulze A., Schieck A., Gahler C. et al. Preclinical studies on Myrcludex B, a novel Hepatitis B virus (HBV) –envelope protein derived entry inhibitor. Zeitschrift fur Gastroenterologie 2010; 48(1). https://dx.doi.org/10.1055/s-0029-1246535.
  32. Soriano V., Moreno-Torres V., Trevino A. et al. Bulevirtide in the treatment of hepatitis delta: Drug discovery, clinical development and place in therapy. Drug Des Devel Ther. 2023; 17: 155–66. https://dx.doi.org/10.2147/DDDT.S379964.
  33. Bogomolov P., Alexandrov A., Voronkova N. 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): 490–98. https://dx.doi.org/10.1016/j.jhep.2016.04.016.
  34. Rizetto M., Niro G. Myrcludex B, a novel therapy for chronic hepatitis D? J Hepatol. 2016; 65(3): 465–66. https://dx.doi.org/10.1016/j.jhep.2016.06.014.
  35. Wedemeyer H., Bogomolov P., Blank A., et. al. Final results of a multicenter open-label phase 2b clinical trial to assess safety and efficacy of Myrcludex B in combination with enofovir in patients with chronic HBV/HDV infection. J Hepatol. 2018;68(1):S3. doi: 10.1016/S0168-8278(18)30224-1.
  36. Wedemeyer H., Schöneweis K., Bogomolov P., et al. Safety and efficacy of bulevirtide in combination with tenofovir disoproxil fumarate in patients with hepatitis B virus and hepatitis D virus coinfection (MYR202): a multicentre, randomised, parallel-group, open-label, phase 2 trial. Lancet Infect Dis. 2023 Jan;23(1):117-129. doi: 10.1016/S1473-3099(22)00318-8.
  37. Богомолов П.О., Ивашкин В.Т., Буеверов А.О. с соавт. Эффективность и безопасность булевиртида в лечении хронического гепатита D: результаты рандомизированных контролируемых исследований. Инфекционные болезни. 2020; 18(4): 153–162. [Bogomolov P.О., Ivashkin V.T., Bueverov А.О., Syutkin V.Е., Sagalova O.I., Sleptsova S.S., Yushuk N.D. et al. Efficacy and safety of bulevirtide in the treatment of chronic hepatitis D: Results of randomized controlled trials. Infektsionnyye bolezni = Infectious Diseases. 2020; 18(4): 153–162 (In Russ.). https://dx.doi.org/10.20953/1729-9225-2020-4-153-162. EDN: ITCBJT.
  38. Asselah A., Arama S., Bogomolov P. et al. Safety and efficacy of bulevirtide monotherapy and in combination with Peginterferon alfa-2a in patients with chronic hepatitis delta: 24-week interim data of MYR204 Phase 2b study. J Hepatol. 2021;75: S291, OS-2717.
  39. Wedemeyer H., Schoneweis K., Bogomolov P. et al. 48 weeks of high dose (10 mg) bulevirtide as monotherapy or with peginterferon alfa-2a in patients with chronic HBV/HDV co-infection. J Hepatol. 2020; 73(2): 52–53. https://dx.doi.org/10.1016/S0168-8278(20)30651-6.
  40. ClinicalTrials.gov. Study to assess efficacy and safety of bulevirtide in participants with chronic hepatitis delta (CHD). URL: http://clinicaltrials.gov/show/NCT03852719 (date of access – 01.04.2023).
  41. Wedemeyer H., Aleman S., Andreone P., Blank A. Bulevirtide monotherapy at low and high dose in patients with chronic hepatitis delta: 24-week interim data of the phase 3 MYR301 study. Dig Liver Dis. 2022; 54: S24–S25. https://dx.doi.org/10.1016/j.dld.2022.01.047.
  42. URL: https://www.ema.europa.eu/en/medicines/human/EPAR/hepcludex (date of access – 01.04.2023).
  43. Богомолов П.О., Ивашкин В.Т., Буеверов А.О. с соавт. Эффективность и безопасность противовирусной терапии у пациентов с компенсированным циррозом печени HDV-этиологии. Терапевтический архив. 2021; 93(11): 1290–1299. [Bogomolov P.O., Ivashkin V.T., Bueverov A.O. et al. Efficacy and safety of antiviral therapy in patients with compensated cirrhosis of the liver of HDV etiology. Terapevticheskiy arkhiv = Therapeutic Archive. 2021;93(11): 2021; 93(11): 1290–1299 (In Russ)]. https://dx.doi.org/10.26442/00403660.2021.11.201163. EDN: VSHZUY.
  44. Schwarz C., Chromy D., Bangert C. et al. Immediate-type hypersensitivity reaction to bulevirtide and successful desensitization in a patient with HBV/HDV-associated compensated cirrhosis. J Hepatol. 2022; 77(1): 254–55. https://dx.doi.org/10.1016/j.jhep.2022.03.004.
  45. Asselah T., Loureiro D., Le Gal F. et al. Early virological response in six patients with hepatitis D virus infection and compensated cirrhosis treated with Bulevirtide in real-life. Liver Int. 2021; 41(7): 1509–17. https://dx.doi.org/10.1111/liv.14950.
  46. De Ledinghen V., Hermabessiere P., Metivier S. et al. Bulevirtide with or without peginterferon in HDV infected patients in a real-life setting: Two-year results from the French multicenter early access program. Hepatology. 2022; 76(Abstract): 28.
  47. Zoulim F., Fougerou C., Roulot D. et al. Efficacy and safety of treatment with bulevirtide in chronic hepatitis delta: preliminary results of the real-life ANRS HD EP01 Buledelta cohort. Hepatology. 2022; 76(Abstract): 1017.
  48. Degasperi E., Anolli M.P., Uceda-Renteria S.C. et al. Improvement of clinical parameters in HDV patients with advanced compensated cirrhosis treated with bulevirtide monotherapy for 48 weeks. Hepatology. 2022; 76(Abstract): 1011.
  49. Degasperi E., Anolli M., Renteria S. et al. Bulevirtide monotherapy for 48 weeks in patients with HDV-related compensated cirrhosis and clinically significant portal hypertension. J Hepatol. 2022; 77(6): 1525–31. https://dx.doi.org/10.1016/j.jhep.2022.07.016.
  50. Jachs M., Schwarz C., Panzer M. et al. Jachs M., Schwarz C., Panzer M. et al. Response-guided long-term treatment of chronic hepatitis D patients with bulevirtide-results of a «real world» study. Aliment Pharmacol Ther. 2022; 56(1): 144–54. https://dx.doi.org/10.1111/apt.16945.
  51. Zollner C., Hofmann J., Lutz K. et al. Real-life experiences with bulevirtide for the treatment of hepatitis delta-48 weeks data from a German centre. Liver Int. 2022; 42(11): 2403–7. https://dx.doi.org/10.1111/liv.15408.
  52. Магомедова С.А., Абдурахманов Д.Т., Арбулиева Е.А. Опыт монотерапии булевиртидом у пациентов с циррозом печени HDV-этиологии в Республике Дагестан. Инфекционные болезни.2022; 20(2): 112–116. [Magomedova S.A., Abdurakhmanov D.T., Arbulieva E.A. Experience of bulevirtide monotherapy in patients with liver cirrhosis of HBV etiology in the Republic of Dagestan. Infektsionnyye bolezni = Infectious Diseases. 2022; 20(2): 112–116 (In Russ.)]. https://dx.doi.org/10.20953/1729-9225-2022-2-112-116. EDN: YASLOJ.
  53. Атмурзаева Д.Т., Иванова М.Р. Опыт противовирусной терапии хронического гепатита D в Кабардино-Балкарской Республике. Инфекционные болезни. 2023; 21(1): 59–63. [Atmurzayeva D.T., Ivanova M.R. Experience of antiviral therapy of chronic hepatitis D in the Kabardino-Balkar Republic. Infektsionnyye bolezni = Infectious Diseases. 2023; 21(1): 59–63 (In Russ.)]. https://dx.doi.org/10.20953/1729-9225-2023-1-59-63.
  54. Жданов К.В., Гусев Д.А., Романова С.Ю. с соавт. Эффективность и безопасность булевиртида в лечении хронического гепатита D – опыт реальной практики в Санкт-Петербурге. Инфекционные болезни. 2023; 21(1): 64–69. [Zhdanov K.V., Gusev D.A., Romanova S.Yu. et al. Efficacy and safety of bulevirtide in the treatment of chronic hepatitis D – the experience of real practice in St. Petersburg. Infektsionnyye bolezni = Infectious Diseases. 2023; 21(1): 64–69 (In Russ.)]. https://dx.doi.org/10.20953/1729-9225-2023-1-64-69.
  55. Исаева О.В., Кюрегян К.К., Ильченко Л.Ю. с соавт. Летальные исходы хронического гепатита дельта: клинико-биохимическая и вирусологическая характеристика. Терапия. 2021; 7(4): 48–56. [Isaeva O.V., Kyuregyan K.K., Ilchenko L.Yu. et al. Lethal outcomes of chronic hepatitis delta: clinical, biochemical and virological characteristics. Terapiya = Therapy. 2021; 7(4): 48–56 (In Russ.)]. https://dx.doi.org/10.18565/therapy.2021.4.48-56. EDN: ERQNPH.
  56. Исаева О.В., Ильченко Л.Ю., Сарыглар А.А. с соавт. Течение и исходы хронического вирусного гепатита D у жителей республики Тыва как эндемичного региона. Вопросы вирусологии. 2021; 66(1): 74–83. [Isaeva O.V., Ilchenko L.Yu., Saryglar A.A. et al. The course and outcomes of chronic viral hepatitis D in residents of the Republic of Tyva as an endemic region. Voprosy virusologii = Problems of Virology. 2021; 66(1): 74–83 (In Russ.)]. https://dx.doi.org/10.36233/0507-4088-29. EDN: VUMUEO.
  57. Le Gal F., Brichler S., Sahli R. et al. First international external quality assessment for hepatitis delta virus RNA quantification in plasma. Hepatology. 2016; 64(5): 1483–94. https://dx.doi.org/10.1002/hep.28772.
  58. Hollnberger J., Schlund F., Schoneweis K. et al. Rare cases of non-response in bulevirtide (BLV) treated patients from the MYR-204/301 studies are not associated with the development of BLV resistance. Hepatology. 2021; 74: S426A.
  59. Asselah T., Lampertico P., Aleman S. et al. Bulevirtide monotherapy is safe and well tolerated in patients with chronic hepatitis D: An integrated safety analysis of 48-week data. Hepatology. 2022; 76(Abstract): 1016.
  60. Schwarz C., Chromy D., Bangert C. et al. Immediate-type hypersensitivity reaction to bulevirtide and successful desensitization in a patient with HBV/HDV-associated compensated cirrhosis. J Hepatol. 2022; 77: 254–55. https://dx.doi.org/10.1016/j.jhep.2022.03.00443
  61. Einav S., Glenn J. Prenylation inhibitors: A novel class of antiviral agents. J Antimicrobial Chemother. 2003; 52(6): 883–86. https://dx.doi.org/10.1093/jac/dkg490.
  62. Berndt N., Hamilton A.D., Sebti S.M. Targeting protein prenylation for cancer therapy. Nat Rev Cancer. 2011; 11(11): 775–91. https://dx.doi.org/10.1038/nrc3151.
  63. Mijimolle N., Velasco J., Dubus P. et al. Protein farnesyltransferase in embryogenesis, adult homeostasis, and tumor development. Cancer Cell. 2005; 7(4): 313–24. https://dx.doi.org/10.1016/j.ccr.2005.03.004.
  64. Palsuledesai C.C., Distefano M.D. Protein prenylation: Enzymes, therapeutics, and biotechnology applications. ACS Chem Biol. 2015; 10(1): 51–62. https://dx.doi.org/10.1021/cb500791f.
  65. Yurdaydin C., Idilman R., Choong I. et al. Optimizing the prenylation inhibitor lonafarnib using ritonavir boosting in patients with chronic delta hepatitis. J Hepatol. 2015; 62: S 252. https://dx.doi.org/10.1016/S0168-8278(15)30137-9.
  66. Koh C., Canini L., Dahari H.et al. Oral prenylation inhibition with lonafarnib in chronic hepatitis D infection: A proof-of-concept randomized, double-blind, placebo-controlled phase IIa trial. Lancet Infect Dis. 2015; 15(10): 1167–74. https://dx.doi.org/10.1016/S1473-3099(15)00074-2.
  67. Sandmann L., Cornberg M. Experimental drugs for the treatment of hepatitis D. J Exp Pharmacol. 2021; 13: 461–68. https://dx.doi.org/10.2147/JEP.S235550.
  68. Koh C., Da B.L., Surana P. et al. A phase 2 study of lonafarnib, ritonavir and peginterferon lambda for 24 weeks: Interim end-of-treatment results from the LIFT HDV study. AASLD. 2020.
  69. Vaillant A. Nucleic acid polymers: Broad spectrum antiviral activity, antiviral mechanisms and optimization for the treatment of hepatitis B and hepatitis D infection. Antivir Res. 2016; 133: 32–40. https://dx.doi.org/10.1016/j.antiviral.2016.07.004.
  70. Blanchet M., Sinnathamby V., Vaillant A., Labonte P. Inhibition of HBsAg secretion by nucleic acid polymers in HepG2.2.15 cells. Antiviral Res. 2019; 164: 97–105. https://dx.doi.org/10.1016/j.antiviral.2019.02.009.
  71. Bazinet M., Pantea 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. https://dx.doi.org/10.1016/S2468-1253(17)30288-1. Erratum in: Lancet Gastroenterol Hepatol. 2018; 3(1): e1.
  72. Noordeen F., Scougall C.A., Grosse A. et al Therapeutic antiviral effect of the nucleic acid polymer rep 2055 against persistent duck hepatitis B virus infection. PLoS One. 2015; 10(11): e0140909. https://dx.doi.org/10.1371/journal.pone.0140909.
  73. Noordeen F., Vaillant A., Jilbert A.R. Nucleic acid polymers prevent the establishment of duck hepatitis B virus infection in vivo. Antimicrob Agents Chemother. 2013; 57(11): 5299–306. https://dx.doi.org/10.1128/AAC.01005-13.
  74. Durantel D., Asselah T. Nucleic acid polymers are effective in targeting hepatitis B surface antigen, but more trials are needed. Gastroenterology. 2020; 158(8): 2051–54. https://dx.doi.org/10.1053/j.gastro.2020.04.020.
  75. Clemmons R. M., Stewart C., Davis G. et al Development of a prototype, rapid saliva test for hepatitis B surface antigen (HBSAg) utilizing a «dipstick» method. Ann N Y Acad Sci. 1993; 694: 272–73. https://dx.doi.org/10.1111/j.1749-6632.1993.tb18361.x.
  76. Bazinet M., Pantea V., Cebotarescu V. et al. Persistent control of hepatitis B virus and hepatitis delta virus infection following REP 2139-Ca and pegylated interferon therapy in chronic hepatitis B virus/hepatitis delta virus coinfection. Hepatol Commun. 2021; 5(2): 189–202. https://dx.doi.org/10.1002/hep4.1633.

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