Ровно 30 лет назад был идентифицирован вирус гепатита С. За эти годы достигнут огромный успех в лечении гепатита С, который в настоящее время рассматривается как практически полностью излечимое заболевание. В обзоре представлены основные этапы становления противовирусной терапии гепатита С, эффективность различных схем лечения. Наибольший прогресс в лечении отмечен в течение последних 5 лет, когда появились и стали широко применяться, в том числе и в России, препараты с прямым противовирусным действием, которые обеспечивают элиминацию вируса в 90–95% случаев.
Exactly 30 years ago, hepatitis C virus was identified. Over the years, tremendous success has been achieved in the treatment of hepatitis C, which is currently considered to be an almost completely curable disease. The review presents the main stages in the development of hepatitis C antiviral therapy, the efficacy of various treatment regimens. The greatest progress in treatment was noted over the past 5 years when drugs with direct antiviral action appeared and began to be widely used, including in Russia, which ensure the elimination of the virus in 90–95% of cases.
1. Feinstone SM, Kapikian AZ, Purcell RH, Alter HJ, Holland PV. Transfusion-associated hepatitis not due to viral hepatitis type A or B. N Engl J Med. 1975;292,767-70. doi: 10.10 56/NEJM197504102921502
2. Berman M, Alter HJ, Ishak KG, Purcell RH, Jones EA. The chronic sequelae of non-A, non-B hepatitis. Ann Intern Med. 1979;91:1-6. doi: 10.7326/0003-4819-91-1-1
3. Сергиев П.Г., Тареев Е.М., Гонтаева А.А. и др. Вирусная желтуха (эпидемический гепатит в связи с иммунизацией человеческой сывороткой). Терапевтический архив. 1940;17(6):596-611 [Sergiev PG, Tareev EM, Gontaeva AA, et al. Viral jaundice (epidemic hepatitis after immunization by human serum). Therapeutic Archive. 1940;17(6):596-611 (In Russ.)].
4. Choo QL, Kuo G, Weiner AJ, et al. Isolation of a cDNA clone derived from a blood-borne non-A, non-B viral hepatitis genome. Science. 1989;244:359-62. doi: 10.1126/science.2523562
5. Marcellin P. Hepatitis B and hepatitis C in 2009. Liver International. 2009;29(s1):1-8. doi: 10.1111/j.1478-3231.2008.01947.x
6. Cooke G, Andrieux-Meyer I, Applegate T, et al. Accelerating the elimination of viral hepatitis: a Lancet Gastroenterology & Hepatology Commission. Lancet Gastroenterol Hepatol. 2019;4:135-84. doi: 10.1016/S2468-1253(18)30270-X
7. Davis GL, Balart LA, Schiff ER, Lindsay K, et al. Treatment of chronic hepatitis C with recombinant interferon alfa. A multicenter randomized, controlled trial. Hepatitis Interventional Therapy Group. N Eng J Med. 1989;321(22):1501-06. doi: 10.1056/NEJM198911303212203
8. Brillanti S, Garson J, Foli M, Whitby K, et al. A pilot study of combination therapy with ribavirin plus interferon alfa for interferon alfa-resistant chronic hepatitis C. Gastroenterology. 1994; 107(3):812-7. doi: 10.1016/0016-5085(94)90131-7
9. Manns MP, McHutchison JG, Gordon SC, Rustgi VK, et al. Peginterferon alfa-2b plus ribavirin compared with interferon alfa-2b plus ribavirin for initial treatment of chronic hepatitis C: a randomised trial. Lancet. 2001;358(22):958-65. doi: 10.1016/s0140-6736(01)06102-5
10. Fried MW, Shiffman ML, Reddy KR, Smith C, Marinos G, et al. Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection. N Engl J Med. 2002;347(13):975-82. doi: 10.1056/NEJMoa020047
11. Nahon P, Bourcier V, Layese R, Audureau E, Cagnot C, et al. Eradication of Hepatitis C Virus Infection in Patients With Cirrhosis Reduces Risk of Liver and Non-Liver Complications. Gastroenterology. 2017;152(1):142-56. doi: 10.1053/j.gastro
12. Simmons B, Saleem J, Heath K, et al. Long-term treatment outcomes of patients infected with hepatitis C virus: a systematic review and meta-analysis of the survival benefit of achieving a sustained virological response. Clin Infect Dis. 2015;61:730-40. doi: 10.1093/cid/civ396
13. Poordad F, McCone J, Bacon BR, Bruno S, et al. Boceprevir for Untreated Chronic HCV Genotype 1 Infection. N Engl J Med. 2011;364:1195-206. doi: 10.1056/NEJMoa1010494
14. Jacobson IM, McHutchison JG, Dusheiko G, Di Bisceglie AM, et al. N Engl J Med. 2011;364:2405-16. doi: 10.1056/NEJMoa1012912
15. Colombo M, Fernández I, Abdurakhmanov D, Ferreira РА, et al. Safety and on-treatment efficacy of telaprevir: the early access programme for patients with advanced hepatitis C. Gut. 2014;63:1150-8. doi: 10.1136/gutjnl-2013-305667
16. Jacobson I, Zeuzem S, Flisiak R, Knysz B, et al. Daclatasvir vs telaprevir plus peginterferon alfa/ribavirin for hepatitis C virus genotype 1. World J Gastroenterol. 2016;22(12):3418-31. doi: 10.3748/wjg.v22.i12.3418
17. Lawitz E, Sulkowski MS, Ghalib R, Rodriguez-Torres M, 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. doi: 10.1016/S0140-6736(14)61036-9
18. Manns M, Pol S, Jacobson IM, Marcellin P, et al. All-oral daclatasvir plus asunaprevir for hepatitis C virus genotype 1b: a multinational, phase 3, multicohort study. Lancet. 2014; 384(9954):1597-605. doi: 10.1016/S0140-6736(14)61059-X
19. Feld JJ, Kowdley KV, Coakley E, Sigal S, et al. Treatment of HCV with ABT-450/r–Ombitasvir and Dasabuvir with Ribavirin. N Engl J Med. 2014;370:1594-603. doi: 10.1056/NEJMoa13157 22
20. Sulkowski MS, Gardiner DF, Rodriguez-Torres M, Reddy KR, et al. Daclatasvir plus Sofosbuvir for Previously Treated or Untreated Chronic HCV Infection. N Engl J Med. 2014;370:211-21. doi: 10.1056/NEJMoa1306218
21. Isakov V, Chulanov V, Abdurakhmanov D, Burnevich E, et al. Sofosbuvir/velpatasvir for the treatment of HCV: excellent results from a phase-3, open-label study in Russia and Sweden. Infect Dis (Lond). 2019;51(2):131-9. doi: 10.1080/23744235.2018.1535186
22. Jacobson IM, Lawitz E, Gane EJ, Willems BE, et al. Efficacy of 8 Weeks of Sofosbuvir, Velpatasvir, and Voxilaprevir in Patients With Chronic HCV Infection: 2 Phase 3 Randomized Trials. Gastroenterology. 2017;153(1):113-22. doi: 10.1053/j.gastro.2017.03.047
23. Zeuzem S, Foster GR, Wang S, Asatryan A, et al. Glecaprevir-Pibrentasvir for 8 or 12 Weeks in HCV Genotype 1 or 3 Infection. N Engl J Med. 2018;378(4):354-69. doi: 10.1056/NEJ Moa1702417
24. Bourlière M, Gordon SC, Flamm SL, Cooper CL, et al. Sofosbuvir, Velpatasvir, and Voxilaprevir for Previously Treated HCV Infection. N Engl J Med. 2017;376:2134-46. doi: 10.1056/NEJMoa1613512
25. Poordad F, Felizarta F, Asatryan A, Sulkowski MS, et al. Glecaprevir and pibrentasvir for 12 weeks for hepatitis C virus genotype 1 infection and prior direct-acting antiviral treatment. Hepatology. 2017;66(2):389-97. doi: 10.1002/hep.29081
26. Abdurakhmanov DT, Rozina TP, Nikulkina EN, Nabatchikova EA, Chulanov VP, Moiseev SV. Sofosbuvir-based salvage therapy for HCV infection in cirrhotic patients with DAA failure and multidrug resistance. Antivir Ther. 2018;23(8):705-8. doi: 10.3851/IMP3266
27. Artemova M, Abdurakhmanov D, Ignatova T, Mukhin N. Persistent Hepatitis C Virus–Associated Cryoglobulinemic Vasculitis Following Virus Eradication After Direct-Acting Antiviral Therapy. Hepatology. 2017;65(5):1770-71. doi: 10.1002/hep.28981
28. Zubkin ML, Abdurakhmanov DT, Sagalova OI, Bakulin IG, Maevskaya MV, Ivashkin VT. Persistent mixed cryoglobulinemia after successful antiviral treatment of chronic hepatitis C virus infection: What's the next? Scandinavian J Gastroenterology. 2018;53(7):883-4. doi: 10. 1080/00365521.2018.1477988
29. Gragnani L, Visentini M, Fognani E, Urraro T, et al. Prospective study of guideline-tailored therapy with direct-acting antivirals for hepatitis C virus–associated mixed cryoglobulinemia. Hepatology. 2016;64:1473-82. doi: 10.1002/hep.28753
30. Calvaruso V, Cabibbo G, Cacciola I, Petta S, et al. Incidence of Hepatocellular Carcinoma in Patients With HCV-Associated Cirrhosis Treated With Direct-Acting Antiviral Agents. Gastroenterology. 2018;155(2):411-21. doi: 10.1053/j.gastro.2018.04.008
31. Lleo A, Aglitti A, Aghemo A, Maisonneuve P, et al. Predictors of hepatocellular carcinoma in HCV cirrhotic patients treated with direct acting antivirals. Dig Liver Dis. 2019;51(2):310-17. doi: 10.1016/j.dld.2018.10.014
32. Ioannou GN, Green PK, Berry K. HCV eradication induced by direct-acting antiviral agents reduces the risk of hepatocellular carcinoma. J Hepatol. 2018;68:25-32. doi.org: 10.1016/j.jhep.2017.08.030
33. Höner Zu Siederdissen C, Maasoumy B, Marra F, Deterding K, et al. Drug-Drug Interactions With Novel All Oral Interferon-Free Antiviral Agents in a Large Real-World Cohort. Clin Infect Dis. 2016;62(5):561-7. doi: 10.1093/cid/civ973
34. Hudson B, Walker AJ, Irving WL. Comorbidities and medications of patients with chronic hepatitis C under specialist care in the UK. J Med Virol. 2017;89(12):2158-64. doi: 10.1002/jmv.24848
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1. Feinstone SM, Kapikian AZ, Purcell RH, Alter HJ, Holland PV. Transfusion-associated hepatitis not due to viral hepatitis type A or B. N Engl J Med. 1975;292,767-70. doi: 10.10 56/NEJM197504102921502
2. Berman M, Alter HJ, Ishak KG, Purcell RH, Jones EA. The chronic sequelae of non-A, non-B hepatitis. Ann Intern Med. 1979;91:1-6. doi: 10.7326/0003-4819-91-1-1
3. [Sergiev PG, Tareev EM, Gontaeva AA, et al. Viral jaundice (epidemic hepatitis after immunization by human serum). Therapeutic Archive. 1940;17(6):596-611 (In Russ.)].
4. Choo QL, Kuo G, Weiner AJ, et al. Isolation of a cDNA clone derived from a blood-borne non-A, non-B viral hepatitis genome. Science. 1989;244:359-62. doi: 10.1126/science.2523562
5. Marcellin P. Hepatitis B and hepatitis C in 2009. Liver International. 2009;29(s1):1-8. doi: 10.1111/j.1478-3231.2008.01947.x
6. Cooke G, Andrieux-Meyer I, Applegate T, et al. Accelerating the elimination of viral hepatitis: a Lancet Gastroenterology & Hepatology Commission. Lancet Gastroenterol Hepatol. 2019;4:135-84. doi: 10.1016/S2468-1253(18)30270-X
7. Davis GL, Balart LA, Schiff ER, Lindsay K, et al. Treatment of chronic hepatitis C with recombinant interferon alfa. A multicenter randomized, controlled trial. Hepatitis Interventional Therapy Group. N Eng J Med. 1989;321(22):1501-06. doi: 10.1056/NEJM198911303212203
8. Brillanti S, Garson J, Foli M, Whitby K, et al. A pilot study of combination therapy with ribavirin plus interferon alfa for interferon alfa-resistant chronic hepatitis C. Gastroenterology. 1994; 107(3):812-7. doi: 10.1016/0016-5085(94)90131-7
9. Manns MP, McHutchison JG, Gordon SC, Rustgi VK, et al. Peginterferon alfa-2b plus ribavirin compared with interferon alfa-2b plus ribavirin for initial treatment of chronic hepatitis C: a randomised trial. Lancet. 2001;358(22):958-65. doi: 10.1016/s0140-6736(01)06102-5
10. Fried MW, Shiffman ML, Reddy KR, Smith C, Marinos G, et al. Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection. N Engl J Med. 2002;347(13):975-82. doi: 10.1056/NEJMoa020047
11. Nahon P, Bourcier V, Layese R, Audureau E, Cagnot C, et al. Eradication of Hepatitis C Virus Infection in Patients With Cirrhosis Reduces Risk of Liver and Non-Liver Complications. Gastroenterology. 2017;152(1):142-56. doi: 10.1053/j.gastro
12. Simmons B, Saleem J, Heath K, et al. Long-term treatment outcomes of patients infected with hepatitis C virus: a systematic review and meta-analysis of the survival benefit of achieving a sustained virological response. Clin Infect Dis. 2015;61:730-40. doi: 10.1093/cid/civ396
13. Poordad F, McCone J, Bacon BR, Bruno S, et al. Boceprevir for Untreated Chronic HCV Genotype 1 Infection. N Engl J Med. 2011;364:1195-206. doi: 10.1056/NEJMoa1010494
14. Jacobson IM, McHutchison JG, Dusheiko G, Di Bisceglie AM, et al. N Engl J Med. 2011;364:2405-16. doi: 10.1056/NEJMoa1012912
15. Colombo M, Fernández I, Abdurakhmanov D, Ferreira РА, et al. Safety and on-treatment efficacy of telaprevir: the early access programme for patients with advanced hepatitis C. Gut. 2014;63:1150-8. doi: 10.1136/gutjnl-2013-305667
16. Jacobson I, Zeuzem S, Flisiak R, Knysz B, et al. Daclatasvir vs telaprevir plus peginterferon alfa/ribavirin for hepatitis C virus genotype 1. World J Gastroenterol. 2016;22(12):3418-31. doi: 10.3748/wjg.v22.i12.3418
17. Lawitz E, Sulkowski MS, Ghalib R, Rodriguez-Torres M, 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. doi: 10.1016/S0140-6736(14)61036-9
18. Manns M, Pol S, Jacobson IM, Marcellin P, et al. All-oral daclatasvir plus asunaprevir for hepatitis C virus genotype 1b: a multinational, phase 3, multicohort study. Lancet. 2014; 384(9954):1597-605. doi: 10.1016/S0140-6736(14)61059-X
19. Feld JJ, Kowdley KV, Coakley E, Sigal S, et al. Treatment of HCV with ABT-450/r–Ombitasvir and Dasabuvir with Ribavirin. N Engl J Med. 2014;370:1594-603. doi: 10.1056/NEJMoa13157 22
20. Sulkowski MS, Gardiner DF, Rodriguez-Torres M, Reddy KR, et al. Daclatasvir plus Sofosbuvir for Previously Treated or Untreated Chronic HCV Infection. N Engl J Med. 2014;370:211-21. doi: 10.1056/NEJMoa1306218
21. Isakov V, Chulanov V, Abdurakhmanov D, Burnevich E, et al. Sofosbuvir/velpatasvir for the treatment of HCV: excellent results from a phase-3, open-label study in Russia and Sweden. Infect Dis (Lond). 2019;51(2):131-9. doi: 10.1080/23744235.2018.1535186
22. Jacobson IM, Lawitz E, Gane EJ, Willems BE, et al. Efficacy of 8 Weeks of Sofosbuvir, Velpatasvir, and Voxilaprevir in Patients With Chronic HCV Infection: 2 Phase 3 Randomized Trials. Gastroenterology. 2017;153(1):113-22. doi: 10.1053/j.gastro.2017.03.047
23. Zeuzem S, Foster GR, Wang S, Asatryan A, et al. Glecaprevir-Pibrentasvir for 8 or 12 Weeks in HCV Genotype 1 or 3 Infection. N Engl J Med. 2018;378(4):354-69. doi: 10.1056/NEJ Moa1702417
24. Bourlière M, Gordon SC, Flamm SL, Cooper CL, et al. Sofosbuvir, Velpatasvir, and Voxilaprevir for Previously Treated HCV Infection. N Engl J Med. 2017;376:2134-46. doi: 10.1056/NEJMoa1613512
25. Poordad F, Felizarta F, Asatryan A, Sulkowski MS, et al. Glecaprevir and pibrentasvir for 12 weeks for hepatitis C virus genotype 1 infection and prior direct-acting antiviral treatment. Hepatology. 2017;66(2):389-97. doi: 10.1002/hep.29081
26. Abdurakhmanov DT, Rozina TP, Nikulkina EN, Nabatchikova EA, Chulanov VP, Moiseev SV. Sofosbuvir-based salvage therapy for HCV infection in cirrhotic patients with DAA failure and multidrug resistance. Antivir Ther. 2018;23(8):705-8. doi: 10.3851/IMP3266
27. Artemova M, Abdurakhmanov D, Ignatova T, Mukhin N. Persistent Hepatitis C Virus–Associated Cryoglobulinemic Vasculitis Following Virus Eradication After Direct-Acting Antiviral Therapy. Hepatology. 2017;65(5):1770-71. doi: 10.1002/hep.28981
28. Zubkin ML, Abdurakhmanov DT, Sagalova OI, Bakulin IG, Maevskaya MV, Ivashkin VT. Persistent mixed cryoglobulinemia after successful antiviral treatment of chronic hepatitis C virus infection: What's the next? Scandinavian J Gastroenterology. 2018;53(7):883-4. doi: 10. 1080/00365521.2018.1477988
29. Gragnani L, Visentini M, Fognani E, Urraro T, et al. Prospective study of guideline-tailored therapy with direct-acting antivirals for hepatitis C virus–associated mixed cryoglobulinemia. Hepatology. 2016;64:1473-82. doi: 10.1002/hep.28753
30. Calvaruso V, Cabibbo G, Cacciola I, Petta S, et al. Incidence of Hepatocellular Carcinoma in Patients With HCV-Associated Cirrhosis Treated With Direct-Acting Antiviral Agents. Gastroenterology. 2018;155(2):411-21. doi: 10.1053/j.gastro.2018.04.008
31. Lleo A, Aglitti A, Aghemo A, Maisonneuve P, et al. Predictors of hepatocellular carcinoma in HCV cirrhotic patients treated with direct acting antivirals. Dig Liver Dis. 2019;51(2):310-17. doi: 10.1016/j.dld.2018.10.014
32. Ioannou GN, Green PK, Berry K. HCV eradication induced by direct-acting antiviral agents reduces the risk of hepatocellular carcinoma. J Hepatol. 2018;68:25-32. doi.org: 10.1016/j.jhep.2017.08.030
33. Höner Zu Siederdissen C, Maasoumy B, Marra F, Deterding K, et al. Drug-Drug Interactions With Novel All Oral Interferon-Free Antiviral Agents in a Large Real-World Cohort. Clin Infect Dis. 2016;62(5):561-7. doi: 10.1093/cid/civ973
34. Hudson B, Walker AJ, Irving WL. Comorbidities and medications of patients with chronic hepatitis C under specialist care in the UK. J Med Virol. 2017;89(12):2158-64. doi: 10.1002/jmv.24848
Клиника ревматологии, нефрологии и профессиональных болезней им. Е.М. Тареева ФГАОУ ВО «Первый Московский государственный медицинский университет им. И.М. Сеченова» Минздрава России (Сеченовский Университет), Москва, Россия