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Эффективность и безопасность противовирусной терапии у пациентов с компенсированным циррозом печени HDV‑этиологии
Эффективность и безопасность противовирусной терапии у пациентов с компенсированным циррозом печени HDV‑этиологии
Богомолов П.О., Ивашкин В.Т., Буеверов А.О., Маев И.В., Сагалова О.И., Слепцова С.С., Ющук Н.Д., Гусев Д.А., Жданов К.В., Чуланов В.П. Эффективность и безопасность противовирусной терапии у пациентов с компенсированным циррозом печени HDV-этиологии. Терапевтический архив. 2021;93(11):1290–1299. DOI: 10.26442/00403660.2021.11.201163
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Аннотация
Цель. Изучение эффективности и безопасности булевиртида – ингибитора проникновения вирусов гепатита B и D в клетку у пациентов с циррозом печени HDV-этиологии.
Материалы и методы. Анализ результатов применения булевиртида в режиме монотерапии и двойной терапии с пегилированным интерфероном альфа-2а (ПЕГ-ИФН) в рандомизированных контролируемых открытых сравнительных исследованиях MYR202 и MYR203 у 56 пациентов с компенсированным циррозом печени в исходе хронического гепатита D.
Результаты. Монотерапия булевиртидом в течение 24 нед в исследовании MYR202 у 46 пациентов с компенсированным циррозом печени продемонстрировала: 1) высокую частоту вирусологического (100%) и биохимического ответа (нормализация аланинаминотрансферазы – 45,7%) на лечении; 2) превосходство булевиртида в эффективности над контрольной группой (тенофовиром); 3) сопоставимость эффективности лечения у пациентов с циррозом и без; 4) отсутствие прогрессирования фиброза печени при эластометрии у большей части пациентов.
Высокая вирусологическая и биохимическая эффективность булевиртида в режиме монотерапии и двойной терапии с ПЕГ-ИФН подтверждена в течение 48 нед в исследовании MYR203 у 10 пациентов с компенсированным циррозом печени: частота вирусологического ответа составила 80%, нормализации аланинаминотрансферазы – 70%.
Отмечалась хорошая переносимость булевиртида, не выявлено ухудшения переносимости по сравнению с пациентами без цирроза, отсутствовали серьезные нежелательные явления и случаи отмены лечения из-за нежелательных явлений.
Заключение. Булевиртид рекомендуется в качестве 1-й линии лечения хронического гепатита D у пациентов с компенсированным циррозом печени в режиме монотерапии и двойной терапии с ПЕГ-ИФН.
Ключевые слова: хронический гепатит D, цирроз печени, булевиртид, монотерапия, двойная терапия с пегилированным интерфероном
Materials and methods. Analysis of the results of using bulevirtide in randomized controlled open-label comparative studies MYR202 and MYR203 in 56 patients with chronic hepatitis D and compensated cirrhosis, in monotherapy and combination with pegylated interferon alpha‑2a (PEG-IFN).
Results. Monotherapy with bulevirtide for 24 weeks in the MYR202 study in 46 patients with compensated liver cirrhosis demonstrated: 1) a high rate of virological (100%) and biochemical response (alanine aminotransferase normalization rate – 45.7%), 2) superiority of bulevirtide in efficacy over the control group (tenofovir), 3) comparability of treatment efficacy in patients with and without cirrhosis, 4) no progression of liver fibrosis with elastometry in most patients.
Treatment with bulevirtide in monotherapy and combination with PEG-IFN for 48 weeks in 10 patients with compensated liver cirrhosis in the MYR203 study was accompanied by a high rate of virological response (80%) and normalization of alanine aminotransferase (70%).
Bulevirtide was well tolerated, there was no deterioration in tolerability compared with patients without cirrhosis, there were no serious adverse events and cases of treatment cancellation due to adverse events.
Conclusion. Bulevirtide is recommended as the first line of treatment for chronic hepatitis D in patients with compensated cirrhosis in monotherapy and combination with PEG-IFN.
Keywords: chronic hepatitis D, liver cirrhosis, bulevirtide, monotherapy, combined therapy with pegylated interferon
Материалы и методы. Анализ результатов применения булевиртида в режиме монотерапии и двойной терапии с пегилированным интерфероном альфа-2а (ПЕГ-ИФН) в рандомизированных контролируемых открытых сравнительных исследованиях MYR202 и MYR203 у 56 пациентов с компенсированным циррозом печени в исходе хронического гепатита D.
Результаты. Монотерапия булевиртидом в течение 24 нед в исследовании MYR202 у 46 пациентов с компенсированным циррозом печени продемонстрировала: 1) высокую частоту вирусологического (100%) и биохимического ответа (нормализация аланинаминотрансферазы – 45,7%) на лечении; 2) превосходство булевиртида в эффективности над контрольной группой (тенофовиром); 3) сопоставимость эффективности лечения у пациентов с циррозом и без; 4) отсутствие прогрессирования фиброза печени при эластометрии у большей части пациентов.
Высокая вирусологическая и биохимическая эффективность булевиртида в режиме монотерапии и двойной терапии с ПЕГ-ИФН подтверждена в течение 48 нед в исследовании MYR203 у 10 пациентов с компенсированным циррозом печени: частота вирусологического ответа составила 80%, нормализации аланинаминотрансферазы – 70%.
Отмечалась хорошая переносимость булевиртида, не выявлено ухудшения переносимости по сравнению с пациентами без цирроза, отсутствовали серьезные нежелательные явления и случаи отмены лечения из-за нежелательных явлений.
Заключение. Булевиртид рекомендуется в качестве 1-й линии лечения хронического гепатита D у пациентов с компенсированным циррозом печени в режиме монотерапии и двойной терапии с ПЕГ-ИФН.
Ключевые слова: хронический гепатит D, цирроз печени, булевиртид, монотерапия, двойная терапия с пегилированным интерфероном
________________________________________________
Materials and methods. Analysis of the results of using bulevirtide in randomized controlled open-label comparative studies MYR202 and MYR203 in 56 patients with chronic hepatitis D and compensated cirrhosis, in monotherapy and combination with pegylated interferon alpha‑2a (PEG-IFN).
Results. Monotherapy with bulevirtide for 24 weeks in the MYR202 study in 46 patients with compensated liver cirrhosis demonstrated: 1) a high rate of virological (100%) and biochemical response (alanine aminotransferase normalization rate – 45.7%), 2) superiority of bulevirtide in efficacy over the control group (tenofovir), 3) comparability of treatment efficacy in patients with and without cirrhosis, 4) no progression of liver fibrosis with elastometry in most patients.
Treatment with bulevirtide in monotherapy and combination with PEG-IFN for 48 weeks in 10 patients with compensated liver cirrhosis in the MYR203 study was accompanied by a high rate of virological response (80%) and normalization of alanine aminotransferase (70%).
Bulevirtide was well tolerated, there was no deterioration in tolerability compared with patients without cirrhosis, there were no serious adverse events and cases of treatment cancellation due to adverse events.
Conclusion. Bulevirtide is recommended as the first line of treatment for chronic hepatitis D in patients with compensated cirrhosis in monotherapy and combination with PEG-IFN.
Keywords: chronic hepatitis D, liver cirrhosis, bulevirtide, monotherapy, combined therapy with pegylated interferon
Полный текст
Список литературы
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7. Wedemeyer H, Yurdaydìn C, Dalekos GN, et al. Peginterferon plus adefovir versus either drug alone for hepatitis delta. N Engl J Med. 2011;364(4):322-31. DOI:10.1056/NEJMoa0912696
8. Scheller L, Hilgard G, Anastasiou O, et al. Poor clinical and virological outcome of nucleos(t)ide analogue monotherapy in HBV/HDV co-infected patients. Medicine (Baltimore). 2021;100(28):e26571. DOI:10.1097/MD.0000000000026571
9. Wedemeyer H, Yurdaydin C, Hardtke S, et al. Peginterferon alfa-2a plus tenofovir disoproxil fumarate for hepatitis D (HIDIT-II): a randomised, placebo controlled, phase 2 trial. Lancet Infect Dis. 2019;19(3):275-86. DOI:10.1016/S1473-3099(18)30663-7
10. Bremer B, Anastasiou O, Hardtke S, et al. Residual low HDV viremia is associated with HDV RNA relapse after PEG-IFNa-based antiviral treatment of hepatitis D (delta): results from the HIDIT-II study. J Hepatol. 2020;73(Suppl. 1):S868.
11. Abdrakhman A, Ashimkhanova A, Almawi WY. Effectiveness of pegylated interferon monotherapy in the treatment of chronic hepatitis D virus infection: A meta-analysis. Antiviral Res. 2021;185:104995. DOI:10.1016/j.antiviral.2020.104995
12. Yan H, Zhong G, Xu G, et al. Sodium taurocholate cotransporting polypeptide is a functional receptor for human hepatitis B and D virus. Elife. 2012;3:10.7554/eLife.00049. DOI:10.7554/eLife.00049
13. 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. DOI:10.1128/JVI.79.3.1613-1622.2005
14. Urban S, Bartenschlager R, Kubitz R, Zoulim F. Strategies to inhibit entry of HBV and HDV into hepatocytes. Gastroenterology. 2014;147(1):48-64. DOI:10.1053/j.gastro.2014.04.030
15. Blank A, Markert C, Hohmann N, et al. First-in-human application of the novel hepatitis B and hepatitis D virus entry inhibitor myrcludex B. J Hepatol. 2016;65(3):483-9. DOI:10.1016/j.jhep.2016.04.013
16. Li W, Urban S. Entry of hepatitis B and hepatitis D virus into hepatocytes: Basic insights and clinical implications. J Hepatol. 2016;64(1 Suppl.):S32-S40. DOI:10.1016/j.jhep.2016.02.011
17. Blank A, Eidam A, Haag M, et al. The NTCP-inhibitor Myrcludex B: Effects on Bile Acid Disposition and Tenofovir Pharmacokinetics. Clin Pharmacol Ther. 2018;103(2):341-8. DOI:10.1002/cpt.744
18. Богомолов П.О., Ивашкин В.Т., Буеверов А.О., и др. Эффективность и безопасность булевиртида в лечении хронического гепатита D – результаты рандомизированных контролируемых исследований. Инфекционные болезни. 2020;18:153-62 [Bogomolov PO, Ivashkin VT, Bueverov AO, et al. Efficacy and safety of bulevirtide in the treatment of chronic hepatitis D: results of randomized controlled trials Infekc. bolezni (Infectious diseases). 2020;18:153–62. (in Russian)].
DOI:10.20953/1729-9225-2020-4-153-162
19. Kang C, Syed YY. Bulevirtide: First Approval. Drugs. 2020;80(15):1601-5. DOI:10.1007/s40265-020-01400-1.
20. 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):490-8. DOI:10.1016/j.jhep.2016.04.016
21. 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 tenofovir in patients with chronic HBV/HDV infection. J Hepatol. 2018;68(1):S3.
DOI:10.1016/S0168-8278(18)30224-1
22. Wedemeyer H, Schöneweis K, Bogomolov P, et al. Interim results of a multicentre, open-label phase 2 clinical trial (MYR203) to assess safety and efficacy of Myrcludex B in combination with Peg-Interferon alpha 2a in patients with chronic HBV/HDV co-infection. Hepatology. 2018;68:S11A.
23. Asselah T, Loureiro D, Tout I, Castelnau C, Boyer N, Marcellin P, et al. Future treatments for hepatitis delta virus infection. Liver Int. 2020;40(Suppl. 1):54-60. DOI:10.1111/liv.14356
24. Sandmann L, Cornberg M. Experimental Drugs for the Treatment of Hepatitis D. J Exp Pharmacol. 2021;13:461-8. DOI:10.2147/JEP.S235550
25. 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. DOI:10.1016/j.jhep.2018.12.022
26. Zhang Z, Urban S. New insights into HDV persistence: The role of interferon response and implications for upcoming novel therapies. J Hepatol. 2021;74(3):686-99. DOI:10.1016/j.jhep.2020.11.032
27. Rizzetto M, Hamid S, Negro F. The changing context of hepatitis D. J Hepatol. 2021;74(5):1200-11. DOI:10.1016/j.jhep.2021.01.014
28. Urban S, Neumann-Haefelin C, Lampertico P. Hepatitis D virus in 2021: virology, immunology and new treatment approaches for a difficult-to-treat disease. Gut. 2021;70(9):1782-94. DOI:10.1136/gutjnl-2020-323888
29. Loglio A, Ferenci P, Renteria S, et al. Excellent safety and effectiveness of high-dose myrcludex-B monotherapy administered for 48 weeks in HDV-related compensated cirrhosis: A case report of 3 patients. J Hepatol. 2019;71(4):834-9. DOI:10.1016/j.jhep.2019.07.003
30. 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. DOI:10.1111/liv.14950
31. Masetti C, Aghemo A. Bulevirtide for treatment of patients with HDV infection and compensated cirrhosis: A (huge?) step in the right direction. Liver Int. 2021;41(7):1441-2. DOI:10.1111/liv.14967
2. Stockdale AJ, Kreuels B, Henrion MYR, et al. The global prevalence of hepatitis D virus infection: systematic review and meta-analysis. J Hepatol. 2020;73(3):523-32. DOI:10.1016/j.jhep.2020.04.008
3. 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. 2019;68(3):512-21. DOI:10.1136/gutjnl-2018-316601
4. Da B, Heller T, Koh C. Hepatitis D infection: from initial discovery to current investigational therapies. Gastroenterol Rep (Oxf). 2019;7(4):231-45. DOI:10.1093/gastro/goz023
5. Mentha N, Clément S, Negro F, et al: From virology to new therapies. J Adv Res. 2019;17:3-15. DOI:10.1016/j.jare.2019.03.009
6. Gilman C, Heller T, Koh C. Chronic hepatitis delta: A state-of-the-art review and new therapies. World J Gastroenterol. 2019;25(32):4580‑97. DOI:10.3748/wjg.v25.i32.4580
7. Wedemeyer H, Yurdaydìn C, Dalekos GN, et al. Peginterferon plus adefovir versus either drug alone for hepatitis delta. N Engl J Med. 2011;364(4):322-31. DOI:10.1056/NEJMoa0912696
8. Scheller L, Hilgard G, Anastasiou O, et al. Poor clinical and virological outcome of nucleos(t)ide analogue monotherapy in HBV/HDV co-infected patients. Medicine (Baltimore). 2021;100(28):e26571. DOI:10.1097/MD.0000000000026571
9. Wedemeyer H, Yurdaydin C, Hardtke S, et al. Peginterferon alfa-2a plus tenofovir disoproxil fumarate for hepatitis D (HIDIT-II): a randomised, placebo controlled, phase 2 trial. Lancet Infect Dis. 2019;19(3):275-86. DOI:10.1016/S1473-3099(18)30663-7
10. Bremer B, Anastasiou O, Hardtke S, et al. Residual low HDV viremia is associated with HDV RNA relapse after PEG-IFNa-based antiviral treatment of hepatitis D (delta): results from the HIDIT-II study. J Hepatol. 2020;73(Suppl. 1):S868.
11. Abdrakhman A, Ashimkhanova A, Almawi WY. Effectiveness of pegylated interferon monotherapy in the treatment of chronic hepatitis D virus infection: A meta-analysis. Antiviral Res. 2021;185:104995. DOI:10.1016/j.antiviral.2020.104995
12. Yan H, Zhong G, Xu G, et al. Sodium taurocholate cotransporting polypeptide is a functional receptor for human hepatitis B and D virus. Elife. 2012;3:10.7554/eLife.00049. DOI:10.7554/eLife.00049
13. 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. DOI:10.1128/JVI.79.3.1613-1622.2005
14. Urban S, Bartenschlager R, Kubitz R, Zoulim F. Strategies to inhibit entry of HBV and HDV into hepatocytes. Gastroenterology. 2014;147(1):48-64. DOI:10.1053/j.gastro.2014.04.030
15. Blank A, Markert C, Hohmann N, et al. First-in-human application of the novel hepatitis B and hepatitis D virus entry inhibitor myrcludex B. J Hepatol. 2016;65(3):483-9. DOI:10.1016/j.jhep.2016.04.013
16. Li W, Urban S. Entry of hepatitis B and hepatitis D virus into hepatocytes: Basic insights and clinical implications. J Hepatol. 2016;64(1 Suppl.):S32-S40. DOI:10.1016/j.jhep.2016.02.011
17. Blank A, Eidam A, Haag M, et al. The NTCP-inhibitor Myrcludex B: Effects on Bile Acid Disposition and Tenofovir Pharmacokinetics. Clin Pharmacol Ther. 2018;103(2):341-8. DOI:10.1002/cpt.744
18. Bogomolov PO, Ivashkin VT, Bueverov AO, et al. Efficacy and safety of bulevirtide in the treatment of chronic hepatitis D: results of randomized controlled trials Infekc. bolezni (Infectious diseases). 2020;18:153–62. (in Russian).
DOI:10.20953/1729-9225-2020-4-153-162
19. Kang C, Syed YY. Bulevirtide: First Approval. Drugs. 2020;80(15):1601-5. DOI:10.1007/s40265-020-01400-1.
20. 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):490-8. DOI:10.1016/j.jhep.2016.04.016
21. 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 tenofovir in patients with chronic HBV/HDV infection. J Hepatol. 2018;68(1):S3.
DOI:10.1016/S0168-8278(18)30224-1
22. Wedemeyer H, Schöneweis K, Bogomolov P, et al. Interim results of a multicentre, open-label phase 2 clinical trial (MYR203) to assess safety and efficacy of Myrcludex B in combination with Peg-Interferon alpha 2a in patients with chronic HBV/HDV co-infection. Hepatology. 2018;68:S11A.
23. Asselah T, Loureiro D, Tout I, Castelnau C, Boyer N, Marcellin P, et al. Future treatments for hepatitis delta virus infection. Liver Int. 2020;40(Suppl. 1):54-60. DOI:10.1111/liv.14356
24. Sandmann L, Cornberg M. Experimental Drugs for the Treatment of Hepatitis D. J Exp Pharmacol. 2021;13:461-8. DOI:10.2147/JEP.S235550
25. 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. DOI:10.1016/j.jhep.2018.12.022
26. Zhang Z, Urban S. New insights into HDV persistence: The role of interferon response and implications for upcoming novel therapies. J Hepatol. 2021;74(3):686-99. DOI:10.1016/j.jhep.2020.11.032
27. Rizzetto M, Hamid S, Negro F. The changing context of hepatitis D. J Hepatol. 2021;74(5):1200-11. DOI:10.1016/j.jhep.2021.01.014
28. Urban S, Neumann-Haefelin C, Lampertico P. Hepatitis D virus in 2021: virology, immunology and new treatment approaches for a difficult-to-treat disease. Gut. 2021;70(9):1782-94. DOI:10.1136/gutjnl-2020-323888
29. Loglio A, Ferenci P, Renteria S, et al. Excellent safety and effectiveness of high-dose myrcludex-B monotherapy administered for 48 weeks in HDV-related compensated cirrhosis: A case report of 3 patients. J Hepatol. 2019;71(4):834-9. DOI:10.1016/j.jhep.2019.07.003
30. 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. DOI:10.1111/liv.14950
31. Masetti C, Aghemo A. Bulevirtide for treatment of patients with HDV infection and compensated cirrhosis: A (huge?) step in the right direction. Liver Int. 2021;41(7):1441-2. DOI:10.1111/liv.14967
2. Stockdale AJ, Kreuels B, Henrion MYR, et al. The global prevalence of hepatitis D virus infection: systematic review and meta-analysis. J Hepatol. 2020;73(3):523-32. DOI:10.1016/j.jhep.2020.04.008
3. 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. 2019;68(3):512-21. DOI:10.1136/gutjnl-2018-316601
4. Da B, Heller T, Koh C. Hepatitis D infection: from initial discovery to current investigational therapies. Gastroenterol Rep (Oxf). 2019;7(4):231-45. DOI:10.1093/gastro/goz023
5. Mentha N, Clément S, Negro F, et al: From virology to new therapies. J Adv Res. 2019;17:3-15. DOI:10.1016/j.jare.2019.03.009
6. Gilman C, Heller T, Koh C. Chronic hepatitis delta: A state-of-the-art review and new therapies. World J Gastroenterol. 2019;25(32):4580‑97. DOI:10.3748/wjg.v25.i32.4580
7. Wedemeyer H, Yurdaydìn C, Dalekos GN, et al. Peginterferon plus adefovir versus either drug alone for hepatitis delta. N Engl J Med. 2011;364(4):322-31. DOI:10.1056/NEJMoa0912696
8. Scheller L, Hilgard G, Anastasiou O, et al. Poor clinical and virological outcome of nucleos(t)ide analogue monotherapy in HBV/HDV co-infected patients. Medicine (Baltimore). 2021;100(28):e26571. DOI:10.1097/MD.0000000000026571
9. Wedemeyer H, Yurdaydin C, Hardtke S, et al. Peginterferon alfa-2a plus tenofovir disoproxil fumarate for hepatitis D (HIDIT-II): a randomised, placebo controlled, phase 2 trial. Lancet Infect Dis. 2019;19(3):275-86. DOI:10.1016/S1473-3099(18)30663-7
10. Bremer B, Anastasiou O, Hardtke S, et al. Residual low HDV viremia is associated with HDV RNA relapse after PEG-IFNa-based antiviral treatment of hepatitis D (delta): results from the HIDIT-II study. J Hepatol. 2020;73(Suppl. 1):S868.
11. Abdrakhman A, Ashimkhanova A, Almawi WY. Effectiveness of pegylated interferon monotherapy in the treatment of chronic hepatitis D virus infection: A meta-analysis. Antiviral Res. 2021;185:104995. DOI:10.1016/j.antiviral.2020.104995
12. Yan H, Zhong G, Xu G, et al. Sodium taurocholate cotransporting polypeptide is a functional receptor for human hepatitis B and D virus. Elife. 2012;3:10.7554/eLife.00049. DOI:10.7554/eLife.00049
13. 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. DOI:10.1128/JVI.79.3.1613-1622.2005
14. Urban S, Bartenschlager R, Kubitz R, Zoulim F. Strategies to inhibit entry of HBV and HDV into hepatocytes. Gastroenterology. 2014;147(1):48-64. DOI:10.1053/j.gastro.2014.04.030
15. Blank A, Markert C, Hohmann N, et al. First-in-human application of the novel hepatitis B and hepatitis D virus entry inhibitor myrcludex B. J Hepatol. 2016;65(3):483-9. DOI:10.1016/j.jhep.2016.04.013
16. Li W, Urban S. Entry of hepatitis B and hepatitis D virus into hepatocytes: Basic insights and clinical implications. J Hepatol. 2016;64(1 Suppl.):S32-S40. DOI:10.1016/j.jhep.2016.02.011
17. Blank A, Eidam A, Haag M, et al. The NTCP-inhibitor Myrcludex B: Effects on Bile Acid Disposition and Tenofovir Pharmacokinetics. Clin Pharmacol Ther. 2018;103(2):341-8. DOI:10.1002/cpt.744
18. Богомолов П.О., Ивашкин В.Т., Буеверов А.О., и др. Эффективность и безопасность булевиртида в лечении хронического гепатита D – результаты рандомизированных контролируемых исследований. Инфекционные болезни. 2020;18:153-62 [Bogomolov PO, Ivashkin VT, Bueverov AO, et al. Efficacy and safety of bulevirtide in the treatment of chronic hepatitis D: results of randomized controlled trials Infekc. bolezni (Infectious diseases). 2020;18:153–62. (in Russian)].
DOI:10.20953/1729-9225-2020-4-153-162
19. Kang C, Syed YY. Bulevirtide: First Approval. Drugs. 2020;80(15):1601-5. DOI:10.1007/s40265-020-01400-1.
20. 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):490-8. DOI:10.1016/j.jhep.2016.04.016
21. 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 tenofovir in patients with chronic HBV/HDV infection. J Hepatol. 2018;68(1):S3.
DOI:10.1016/S0168-8278(18)30224-1
22. Wedemeyer H, Schöneweis K, Bogomolov P, et al. Interim results of a multicentre, open-label phase 2 clinical trial (MYR203) to assess safety and efficacy of Myrcludex B in combination with Peg-Interferon alpha 2a in patients with chronic HBV/HDV co-infection. Hepatology. 2018;68:S11A.
23. Asselah T, Loureiro D, Tout I, Castelnau C, Boyer N, Marcellin P, et al. Future treatments for hepatitis delta virus infection. Liver Int. 2020;40(Suppl. 1):54-60. DOI:10.1111/liv.14356
24. Sandmann L, Cornberg M. Experimental Drugs for the Treatment of Hepatitis D. J Exp Pharmacol. 2021;13:461-8. DOI:10.2147/JEP.S235550
25. 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. DOI:10.1016/j.jhep.2018.12.022
26. Zhang Z, Urban S. New insights into HDV persistence: The role of interferon response and implications for upcoming novel therapies. J Hepatol. 2021;74(3):686-99. DOI:10.1016/j.jhep.2020.11.032
27. Rizzetto M, Hamid S, Negro F. The changing context of hepatitis D. J Hepatol. 2021;74(5):1200-11. DOI:10.1016/j.jhep.2021.01.014
28. Urban S, Neumann-Haefelin C, Lampertico P. Hepatitis D virus in 2021: virology, immunology and new treatment approaches for a difficult-to-treat disease. Gut. 2021;70(9):1782-94. DOI:10.1136/gutjnl-2020-323888
29. Loglio A, Ferenci P, Renteria S, et al. Excellent safety and effectiveness of high-dose myrcludex-B monotherapy administered for 48 weeks in HDV-related compensated cirrhosis: A case report of 3 patients. J Hepatol. 2019;71(4):834-9. DOI:10.1016/j.jhep.2019.07.003
30. 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. DOI:10.1111/liv.14950
31. Masetti C, Aghemo A. Bulevirtide for treatment of patients with HDV infection and compensated cirrhosis: A (huge?) step in the right direction. Liver Int. 2021;41(7):1441-2. DOI:10.1111/liv.14967
________________________________________________
2. Stockdale AJ, Kreuels B, Henrion MYR, et al. The global prevalence of hepatitis D virus infection: systematic review and meta-analysis. J Hepatol. 2020;73(3):523-32. DOI:10.1016/j.jhep.2020.04.008
3. 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. 2019;68(3):512-21. DOI:10.1136/gutjnl-2018-316601
4. Da B, Heller T, Koh C. Hepatitis D infection: from initial discovery to current investigational therapies. Gastroenterol Rep (Oxf). 2019;7(4):231-45. DOI:10.1093/gastro/goz023
5. Mentha N, Clément S, Negro F, et al: From virology to new therapies. J Adv Res. 2019;17:3-15. DOI:10.1016/j.jare.2019.03.009
6. Gilman C, Heller T, Koh C. Chronic hepatitis delta: A state-of-the-art review and new therapies. World J Gastroenterol. 2019;25(32):4580‑97. DOI:10.3748/wjg.v25.i32.4580
7. Wedemeyer H, Yurdaydìn C, Dalekos GN, et al. Peginterferon plus adefovir versus either drug alone for hepatitis delta. N Engl J Med. 2011;364(4):322-31. DOI:10.1056/NEJMoa0912696
8. Scheller L, Hilgard G, Anastasiou O, et al. Poor clinical and virological outcome of nucleos(t)ide analogue monotherapy in HBV/HDV co-infected patients. Medicine (Baltimore). 2021;100(28):e26571. DOI:10.1097/MD.0000000000026571
9. Wedemeyer H, Yurdaydin C, Hardtke S, et al. Peginterferon alfa-2a plus tenofovir disoproxil fumarate for hepatitis D (HIDIT-II): a randomised, placebo controlled, phase 2 trial. Lancet Infect Dis. 2019;19(3):275-86. DOI:10.1016/S1473-3099(18)30663-7
10. Bremer B, Anastasiou O, Hardtke S, et al. Residual low HDV viremia is associated with HDV RNA relapse after PEG-IFNa-based antiviral treatment of hepatitis D (delta): results from the HIDIT-II study. J Hepatol. 2020;73(Suppl. 1):S868.
11. Abdrakhman A, Ashimkhanova A, Almawi WY. Effectiveness of pegylated interferon monotherapy in the treatment of chronic hepatitis D virus infection: A meta-analysis. Antiviral Res. 2021;185:104995. DOI:10.1016/j.antiviral.2020.104995
12. Yan H, Zhong G, Xu G, et al. Sodium taurocholate cotransporting polypeptide is a functional receptor for human hepatitis B and D virus. Elife. 2012;3:10.7554/eLife.00049. DOI:10.7554/eLife.00049
13. 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. DOI:10.1128/JVI.79.3.1613-1622.2005
14. Urban S, Bartenschlager R, Kubitz R, Zoulim F. Strategies to inhibit entry of HBV and HDV into hepatocytes. Gastroenterology. 2014;147(1):48-64. DOI:10.1053/j.gastro.2014.04.030
15. Blank A, Markert C, Hohmann N, et al. First-in-human application of the novel hepatitis B and hepatitis D virus entry inhibitor myrcludex B. J Hepatol. 2016;65(3):483-9. DOI:10.1016/j.jhep.2016.04.013
16. Li W, Urban S. Entry of hepatitis B and hepatitis D virus into hepatocytes: Basic insights and clinical implications. J Hepatol. 2016;64(1 Suppl.):S32-S40. DOI:10.1016/j.jhep.2016.02.011
17. Blank A, Eidam A, Haag M, et al. The NTCP-inhibitor Myrcludex B: Effects on Bile Acid Disposition and Tenofovir Pharmacokinetics. Clin Pharmacol Ther. 2018;103(2):341-8. DOI:10.1002/cpt.744
18. Bogomolov PO, Ivashkin VT, Bueverov AO, et al. Efficacy and safety of bulevirtide in the treatment of chronic hepatitis D: results of randomized controlled trials Infekc. bolezni (Infectious diseases). 2020;18:153–62. (in Russian).
DOI:10.20953/1729-9225-2020-4-153-162
19. Kang C, Syed YY. Bulevirtide: First Approval. Drugs. 2020;80(15):1601-5. DOI:10.1007/s40265-020-01400-1.
20. 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):490-8. DOI:10.1016/j.jhep.2016.04.016
21. 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 tenofovir in patients with chronic HBV/HDV infection. J Hepatol. 2018;68(1):S3.
DOI:10.1016/S0168-8278(18)30224-1
22. Wedemeyer H, Schöneweis K, Bogomolov P, et al. Interim results of a multicentre, open-label phase 2 clinical trial (MYR203) to assess safety and efficacy of Myrcludex B in combination with Peg-Interferon alpha 2a in patients with chronic HBV/HDV co-infection. Hepatology. 2018;68:S11A.
23. Asselah T, Loureiro D, Tout I, Castelnau C, Boyer N, Marcellin P, et al. Future treatments for hepatitis delta virus infection. Liver Int. 2020;40(Suppl. 1):54-60. DOI:10.1111/liv.14356
24. Sandmann L, Cornberg M. Experimental Drugs for the Treatment of Hepatitis D. J Exp Pharmacol. 2021;13:461-8. DOI:10.2147/JEP.S235550
25. 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. DOI:10.1016/j.jhep.2018.12.022
26. Zhang Z, Urban S. New insights into HDV persistence: The role of interferon response and implications for upcoming novel therapies. J Hepatol. 2021;74(3):686-99. DOI:10.1016/j.jhep.2020.11.032
27. Rizzetto M, Hamid S, Negro F. The changing context of hepatitis D. J Hepatol. 2021;74(5):1200-11. DOI:10.1016/j.jhep.2021.01.014
28. Urban S, Neumann-Haefelin C, Lampertico P. Hepatitis D virus in 2021: virology, immunology and new treatment approaches for a difficult-to-treat disease. Gut. 2021;70(9):1782-94. DOI:10.1136/gutjnl-2020-323888
29. Loglio A, Ferenci P, Renteria S, et al. Excellent safety and effectiveness of high-dose myrcludex-B monotherapy administered for 48 weeks in HDV-related compensated cirrhosis: A case report of 3 patients. J Hepatol. 2019;71(4):834-9. DOI:10.1016/j.jhep.2019.07.003
30. 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. DOI:10.1111/liv.14950
31. Masetti C, Aghemo A. Bulevirtide for treatment of patients with HDV infection and compensated cirrhosis: A (huge?) step in the right direction. Liver Int. 2021;41(7):1441-2. DOI:10.1111/liv.14967
Авторы
П.О. Богомолов*1,2, В.Т. Ивашкин3, А.О. Буеверов1,3, И.В. Маев2, О.И. Сагалова4, С.С. Слепцова5, Н.Д. Ющук2, Д.А. Гусев6, К.В. Жданов7, В.П. Чуланов3,8
1 ГБУЗ МО «Московский областной научно-исследовательский клинический институт им. М.Ф. Владимирского», Москва, Россия;
2 ФГБОУ ВО «Московский государственный медико-стоматологический университет им. А.И. Евдокимова» Минздрава России, Москва, Россия;
3 ФГАОУ ВО «Первый Московский государственный медицинский университет им. И.М. Сеченова» Минздрава России (Сеченовский Университет), Москва, Россия;
4 ФГБОУ ВО «Южно-Уральский государственный медицинский университет» Минздрава России, Челябинск, Россия;
5 ФГАОУ ВО «Северо-Восточный федеральный университет им. М.К. Аммосова», Якутск, Россия;
6 ГБУЗ «Клиническая инфекционная больница им. С.П. Боткина», Санкт-Петербург, Россия;
7 ФГБВОУ ВО «Военно-медицинская академия им. С.М. Кирова» Минобороны России, Санкт-Петербург, Россия;
8 ФГБУ «Национальный медицинский исследовательский центр фтизиопульмонологии и инфекционных заболеваний» Минздрава России, Москва, Россия
*hepatology@monikiweb.ru
1 Vladimirsky Moscow Regional Research Clinical Institute, Moscow, Russia;
2 Yevdokimov Moscow State University of Medicine and Dentistry, Moscow, Russia;
3 Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia;
4 South Ural State Medical University, Chelyabinsk, Russia;
5 Ammosov North-Eastern Federal University, Yakutsk, Russia;
6 Botkin Clinical Infectious Diseases Hospital, Saint Petersburg, Russia;
7 Kirov Military Medical Academy, Saint Petersburg, Russia;
8 National Medical Research Center of Phthisiopulmonology and Infectious Diseases, Moscow, Russia
*hepatology@monikiweb.ru
1 ГБУЗ МО «Московский областной научно-исследовательский клинический институт им. М.Ф. Владимирского», Москва, Россия;
2 ФГБОУ ВО «Московский государственный медико-стоматологический университет им. А.И. Евдокимова» Минздрава России, Москва, Россия;
3 ФГАОУ ВО «Первый Московский государственный медицинский университет им. И.М. Сеченова» Минздрава России (Сеченовский Университет), Москва, Россия;
4 ФГБОУ ВО «Южно-Уральский государственный медицинский университет» Минздрава России, Челябинск, Россия;
5 ФГАОУ ВО «Северо-Восточный федеральный университет им. М.К. Аммосова», Якутск, Россия;
6 ГБУЗ «Клиническая инфекционная больница им. С.П. Боткина», Санкт-Петербург, Россия;
7 ФГБВОУ ВО «Военно-медицинская академия им. С.М. Кирова» Минобороны России, Санкт-Петербург, Россия;
8 ФГБУ «Национальный медицинский исследовательский центр фтизиопульмонологии и инфекционных заболеваний» Минздрава России, Москва, Россия
*hepatology@monikiweb.ru
________________________________________________
1 Vladimirsky Moscow Regional Research Clinical Institute, Moscow, Russia;
2 Yevdokimov Moscow State University of Medicine and Dentistry, Moscow, Russia;
3 Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia;
4 South Ural State Medical University, Chelyabinsk, Russia;
5 Ammosov North-Eastern Federal University, Yakutsk, Russia;
6 Botkin Clinical Infectious Diseases Hospital, Saint Petersburg, Russia;
7 Kirov Military Medical Academy, Saint Petersburg, Russia;
8 National Medical Research Center of Phthisiopulmonology and Infectious Diseases, Moscow, Russia
*hepatology@monikiweb.ru
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