Современные возможности и перспективы повторного лечения больных хроническим гепатитом С


Бацких С.Н., Карандашова И.В., Чула­нов В.П.

1 ФБУН «Центральный НИИ эпидемиологии» Роспотребнадзора, Москва, Россия; 2 ГБУЗ «Московский клинический научно-практический центр имени А.С. Логинова» Департамента здравоохранения города Москвы, Москва, Россия
В статье изложены современные представления об основных факторах, влияющих на успешность лечения больных хроническим гепатитом С. Приведены собственные данные по ключевым показателям, ассоциированным с неэффективностью противовирусной терапии. Проанализированы литературные источники, содержащие результаты клинических исследований разных схем терапии. Обсуждаются возможности, проблемы и перспективы современных вариантов повторного лечения пациентов, не ответивших на первичный курс противовирусной терапии.
Ключевые слова: ингибиторы NS5A, гепатит С, интерферон, ингибиторы полимеразы, ингибиторы протеазы, рибавирин, резистентность, мутации
Полный текст статьи доступен
в "Библиотеке Врача"

Литература

  1. Rong L., Dahari H., Ribeiro R.M., Perelson A.S.. Rapid emergence of protease inhibitor resistance in hepatitis C virus. Sci. Transl. Med. 2010; (2): 30–32.
  2. Manns M., Pol S., Jacobson I., Marcellin P., Gordon S., Peng C.Y. et al. All-oral daclatasvir plus asunaprevir for hepatitis C virus genotype 1b: a multinational, phase 3, multicohort study. Lancet 2014; 384: 1597–1605.
  3. Krishnan P., Tripathi R., Schnell G., Reisch T., Beyer J., Irvin M. et al. Resistance analysis of baseline and treatment-emergent variants in hepatitis C virus genotype 1 in the AVIATOR study with paritaprevir-ritonavir, ombitasvir, and dasabuvir. Antimicrob. Agents Chemother. 2015; 59(9): 5445–54.
  4. Sarrazin C. The importance of resistance to direct antiviral drugs in HCV infection in clinical practice. J. Hepatol. 2016; 64: 486–504.
  5. Pawlotsky J.M. Hepatitis C Virus Resistance to Direct-Acting Antiviral Drugs in Interferon-Free Regimens. Gastroenterology 2016; 151: 70–86.
  6. Chulanov V., Zhdanov K., Kersey K., Zhu Y., Svarovskaia E., Massetto B. et al. Sofosbuvir plus Ribavirin for the treatment of Russian patients with chronic HCV genotype 1 or 3 Infection. Hepatology 2014; 60(1) (Suppl): 676A.
  7. Vermehren J., Susser S., Dietz J., von Hahn T., Petersen J., Hinrichsen H. et al. Retreatment of patients who failed DAA-combination therapies: real-world experience from a large hepatitis C resistance database. J. Hepatol. 2016; 64 (Suppl 2): S188.
  8. EASL Recommendations on Treatment of Hepatitis C 2016. J. Hepatol. 2017; 66: 153–94.
  9. Recommendations for Testing, Managing and Treating Hepatitis C. Changes made April 12, 2017. http://www.hcvguidelines.org
  10. Lawitz E., Sulkowski M.S., Ghalib R., Rodriguez-Torres M., Younossi Z.M., Corregidor A. et al. Simeprevir plus sofosbuvir, with or without ribavirin, to treat chronic infection with hepatitis C virus genotype 1 in non-responders to pegylated interferon and ribavirin and treatment-naive patients: the COSMOS randomised study. Lancet 2014; 384(9956): 1756–65.
  11. Kwo P., Gitlin N., Nahass R., Bernstein D., Etzkorn K., Rojter S. et al. Simeprevir plus sofosbuvir (12 and 8 weeks) in hepatitis C virus genotype 1-infected patients without cirrhosis: OPTIMIST-1, a phase 3, randomized study. Hepatology 2016; 64(2): 370–80.
  12. Lawitz E., Matusow G., DeJesus E., Yoshida E.M., Felizarta F., Ghalib R., et al. Simeprevir plus sofosbuvir in patients with chronic hepatitis C virus genotype 1 infection and cirrhosis: A Phase 3 study (OPTIMIST-2). Hepatology 2016; 64: 360–9.
  13. Dieterich D., Bacon B.R., Flamm S.L., Kowdley K.V., Milligan S., Tsai N. et al. Evaluation of sofosbuvir and simeprevir-based regimens in the TRIO network: academic and community treatment of a real-world, heterogeneous population. Hepatology 2014; 60(1) (Suppl): 220A.
  14. Sulkowski M.S., Gardiner D.F., Rodriguez-Torres M., Rajender Reddy K., Hassanein T., Jacobson I. et al. Daclatasvir plus Sofosbuvir for Previously Treated or Untreated Chronic HCV Infection. N. Engl. J. Med. 2014; 370: 211–21.
  15. Welzel T., Petersen J., Herzer K., Ferenci P., Gschwantler M., Cornberg M. et al. Daclatasvir plus sofosbuvir with or without ribavirin for treatment of chronic HCV infection in patients with advanced liver disease: results of a European compassionate use program. J. Hepatol. 2016; 64 (Suppl 2): S825.
  16. Manns M., Pol S., Jacobson I.M., Marcellin P., Gordon S.C., Peng C.Y. et al. All‐oral daclatasvir plus asunaprevir for hepatitis C virus genotype 1b: a multinational, phase 3, multicohort study. Lancet 2014; 384: 1597–605.
  17. Hong C.-M., Liu C.-J., Yeh S.-H., Chen P.-J. Addition of ribavirin to daclatasvir plus asunaprevir for chronic hepatitis C 1b patients with baseline NS5A resistance-associated variants improved response. Journal of the Formosan Medical Association 2017; 116(4): 295–9.
  18. Suda G., Kudo M., Nagasaka A., Furuya K., Yamamoto Y., Kobayashi T. et al. Efficacy and safety of daclatasvir and asunaprevir combination therapy in chronic hemodialysis patients with chronic hepatitis C. J. Gastroenterol. 2016; 51(7): 733–40.
  19. Dore G.J., Conway B., Luo Y., Janczewska E., Knysz B., Liu Y. et al. Efficacy and safety of ombitasvir/paritaprevir/r and dasabuvir compared to IFN-containing regimens in genotype 1 HCV patients: The MALACHITE-I/II trials. J. Hepatol. 2016; 64: 19–28.
  20. Colombo M., Weiland O., Cohen D.E., Du Four J.F., Reynaert H., Diago M. et al. SVR12 rate of 98.6% in 992 HCV Genotype 1b-infected patients treated with ABT-450/r/Ombitasvir and Dasabuvir with or without Ribavirin. Hepatology 2014; 60(1) (Suppl): 1131A.
  21. Feld J., Moreno C., Trinh R., Tam E., Bourgeois S., Horsmans Y. et al. Sustained virologic response of 100% in HCV genotype 1b patients with cirrhosis receiving ombitasvir/paritaprevir/r and dasabuvir for 12weeks. J. Hepatol. 2016; 64: 301–7.
  22. Sarrazin C, Sulkowski M, Krishnan P, Tripathi R, Schnell G, Xie Y, et al. Effect of baseline resistance-associated variants on SVR with the 3D regimen with and without RBV in GT1A and GT1B-infected patients. J. Hepatol. 2016; 64 (Suppl 2): S214.
  23. Hunyady B., Abonyi M., Gervain J., Horvath G., Gerlei Z., Lengyel G. et al. Ombitasvir/Paritaprevir/Ritonavir + Dasabuvir + Ribavirin (3D + RBV) treatment of hepatitis C (HCV) Genotype 1 (GT1) infected patients (pts) after failure to previous first generation protease-inhibitor (PI) therapy interim analysis. J. Hepatol. 2016; 64 (Suppl 2): S750.
  24. Hinrichsen H., Wedemeyer H., Christensen S., Sarrazin C., Baumgarten A., Mauss S. et al. Real-world safety and effectiveness of Ombitasvir/ Paritaprevir/R with Dasabuvir and/or Ribavirin in the German hepatitis C registry. J. Hepatol. 2016; 64 (Suppl 2): S159.
  25. Poordad F., Bennett M., Sepe, T.E., Cohen E., Reindollar R., Everson G.T. et al. Retreatment of HCV Genotype 1 DAA-failures with Ombitasvir/Paritaprevir/r, Dasabuvir, and Sofosbuvir. Hepatology 2015; 62 (6) (Suppl): 1392A.
  26. Nelson D.R., Cooper J.N., Lalezari J.P., Lawitz E., Pockros P.J., Gitlin N. et al. All-oral 12-week treatment with daclatasvir plus sofosbuvir in patients with hepatitis C virus genotype 3 infection: ALLY-3 phase III study. Hepatology 2015; 61(4): 1127–35.
  27. Leroy V., Angus P., Bronowicki J..P, Dore G.J., Hezode C., Pianko S. et al. Daclatasvir, sofosbuvir, and ribavirin for hepatitis C virus genotype 3 and advanced liver disease: A randomized phase III study (ALLY-3+). Hepatology 2016; 63(5): 1430–41.
  28. Halfon P., Locarnini S. Hepatitis C virus resistance to protease inhibitors. J. Hepatol. 2011; 55: 192–206.
  29. Summa V., Ludmerer S.W., McCauley J.A., Fandozzi C., Burlein C., Claudio G. et al. MK-5172, a selective inhibitor of hepatitis C virus NS3/4a protease with broad activity across genotypes and resistant variants. Antimicrob. Agents Chemother. 2012; 56(8): 4161–7.
  30. Howe A.Y., Black S., Curry S., Ludmerer S.W., Liu R., Barnard R.J. et al. Virologic resistance analysis from a phase 2 study of MK-5172 combined with pegylated interferon/ribavirin in treatment-naive patients with hepatitis C virus genotype 1 infection. Clin. Infect. Dis. 2014; 59 (12): 1657–65.
  31. Kwo P., Gane E., Peng C.Y., Pearlman B., Vireling J., Serfaty L. et al. Efficacy and safety of grazoprevir/elbasvir ± RBV for 12 weeks in patients with HCV G1 or G4 infection who previously failed peginterferon/RBV: C-edge treatment-experienced trial. J. Hepatol. 2015; 62 (Suppl 2): S674–5.
  32. Forns X., Gordon S.C., Zuckerman E., Lawitz E., Calleja J.L., Hofer H. et al. Grazoprevir and elbasvir plus ribavirin for chronic HCV genotype-1 infection after failure of combination therapy containing a direct-acting antiviral agent. J. Hepatol. 2015; 63: 564–72.
  33. Forns X., Gordon S.C., Zuckerman E., Lawitz E., Calleja J.L., Hofer H. et al. Grazoprevir and elbasvir plus ribavirin for chronic HCV genotype-1 infection after failure of combination therapy containing a direct-acting antiviral agent. J. Hepatol. 2015; 63: 564–72.
  34. Lawitz E., Poordad F., Gutierrez J., Wells J., Landaverde C., Reiling J. et al. C-SWIFT Retreatment (Part B): 12 weeks of Elbasvir/Grazoprevir with Sofosbuvir and Ribavirin successfully treated GT1-infected subjects who failed short-duration all-oral therapy. Hepatology 2015; 62(6) (Suppl): 1386–7A.
  35. Foster G.R., Agarwal K., Cramp M., Moreea S., Barclay S.T., Collie J. et al. C-ISLE: Grazoprevir/Elbasvir plus Sofosbuvir in treatment-naive and treatment-experienced HCV GT3 cirrhotic patients treated for 8, 12 or 16 weeks. Hepatology 2016; 64(1) (Suppl): 39–40A.
  36. Feld J.J., Jacobson I.M., Hézode C., Asselah T., Ruane P.J., Gruener N. et al. Sofosbuvir and Velpatasvir for HCV Genotype 1, 2, 4, 5, and 6 Infection. N. Engl. J. Med. 2015; 373(27): 2599–607.
  37. Foster G.R., Afdhal N., Roberts S.K., Bräu N., Gane E.J., Pianko S. et al. Sofosbuvir and Velpatasvir for HCV Genotype 2 and 3 Infection. N. Engl. J. Med. 2015; 373(27): 2608–17.
  38. Pianko S., Flamm S.L., Shiffman M.L., Kumar S., Strasser S.I., Dore G.J. et al. Sofosbuvir plus Velpatasvir combination therapy for treatment-experienced patients with Genotype 1 or 3 hepatitis C virus Infection: a randomized trial. Ann. Intern. Med. 2015; 163(11): 809–17.
  39. Gane E.J., Shiffman M.L., Etzkorn K., Morelli G., Stedman C., Davis M.N. et al. Sofosbuvir/Velpatasvir in Combination with Ribavirin for 24 Weeks is Effective Retreatment for Patients who failed Prior NS5A Containing DAA Regimens: Results of the GS-US-342-1553 Study. J. Hepatol. 2016; 64 (Suppl 2): S147–8.
  40. Zeuzem S., Feld J.J., Wang S., Bourliere M., Wedemeyer H., Gane E.J. et al. ENDURANCE-1: Efficacy and Safety of 8- versus 12-week Treatment with ABT-493/ABT-530 in patients with Chronic HCV Genotype 1 Infection. Hepatology 2016; 64(1) (Suppl): 132–3A.
  41. Kowdley K.V., Colombo M., Zadeikis N., Mantry P.S., Calinas F., Aguilar H.I. et al. ENDURANCE-2: Safety and efficacy of ABT-493/ABT-530 in Hepatitis C virus Genotype 2-infected patients without cirrhosis, a Randomized, double-blind, placebo-controlled study. Hepatology 2016; 64(1) (Suppl): 39A.
  42. Asselah T., Hezode C., Zadeikis N., Elkhashab M., Colombo M., Marinho R.T. et al. ENDURANCE-4: Efficacy and safety of ABT-493/ABT-530 treatment in patients with chronic HCV Genotype 4, 5, or 6 infection. Hepatology 2016; 64(1) (Suppl): 63A.
  43. Wyles D.L., Poordad F., Wang S., Alric L., Felizarta F., Kwo P.Y. et al. SURVEYOR-II, Part 3: Efficacy and safety of ABT-493/ABT-530 in patients with Hepatitis C virus Genotype 3 Infection with prior treatment experience and/or cirrhosis. Hepatology 2016; 64 (1) (Suppl): 62–3A.
  44. Gane E.J., Lawitz E., Pugatch D., Papatheodoridis G.V., Bräu N., Brown A.S. et al. EXPEDITION-IV: Safety and efficacy of GLE/PIB in adults with renal impairment and chronic hepatitis C virus Genotype 1 – 6 Infection. Hepatology 2016; 64(6) (Suppl): 1125A.
  45. Poordad F., Gordon S.C., Asatryan A., Felizarta F., Reindollar R.W., Landis C. et al. High efficacy of ABT-493 and ABT-530 in HCV Genotype 1 infected patients who have failed Direct-Acting Antiviral-containing regimens: the MAGELLAN-I Study. J. Hepatol. 2016; 64 (Suppl 2): S160–1.


Об авторах / Для корреспонденции

Для корреспонденции:
Бацких Сергей Николаевич – к.м.н., старший научный сотрудник отдела гепатологии ГБУЗ «Московский клинический научно-практический центр имени А.С. Логинова» Департамента здравоохранения города Москвы; научный сотрудник ФБУН «Центральный НИИ эпидемиологии» Роспотребнадзора
Адрес: 111123, Москва, ул. Новогиреевская, д. 3а
Телефон: +7(495) 788-00-02 доб. 24-18
E-mail: zdoc@mail.ru

Сведения об авторах:
Карандашова Инга Вадимовна – к.б.н., старший научный сотрудник лаборатории вирусных гепатитов отдела молекулярной диагностики и эпидемиологии ФБУН «Центральный НИИ эпидемиологии» Роспотребнадзора; е-mail: inga.karadashova@pcr.ru
Чуланов Владимир Петрович – д.м.н., заведующий научно-консультативным клинико-диагностическим центром ФБУН «Центральный НИИ эпидемиологии» Роспотребнадзора: е-mail: vladimir.chulanov@pcr.ru


Похожие статьи

К содержанию номера

Бионика Медиа