Проведен анализ состояния проблемы хронического гепатита С у детей. Представлены данные по первичной заболеваемости хроническим гепатитом С у детского населения как на территории Российской Федерации, так и за рубежом. Рассмотрены проблемы диагностики HCV-инфекции. Проведен обзорный анализ риска инфицированности, освещены возможные пути передачи, показаны особенности течения HCV-инфекции у детей, отображена частота хронизации процесса. Проанализировано состояние проблемы в настоящее время и оценены дальнейшие перспективы в лечении хронического вирусного гепатита С у детей.

childrenchronic hepatitis Cinterferonantiviral therapyдетихронический гепатит Спротивовирусная терапияинтерферонотерапия1.1. Brook G., Soriano V., Bergin C. European guideline for the management of hepatitis B and C virus infections. Inter. J. STD & AIDS. 2010; 21 (10): 669–678.2.2. Cornberg M., Razavi H.A., Alberti A., Bernasconi E., Buti M., Cooper C., Dalgard O., Dillion J.F., Flisiak R., Forns X., Frankova S., Goldis A., Goulis I., Halota W., Hunyady B., Lagging M., Largen A., Makara M., Manolakopoulos S., Marcellin P., Marinho R.T., Pol S., Poynard T., Puoti M., Sagalova O., Sibbel S., Simon K., Wallace C., Young K., Yurdaydin C., Zuckerman E., Negro F., Zeuzem S. A systematic review of hepatitis C virus epidemiology in Europe, Canada and Israel. Liver Int. 2011; 31 (2): 30–60.3.3. Indolfi G., Bartolini E., Casavola D., Resti M. Chronic hepatitis C virus infection in children and adolescents: Epidemiology, natural history, and assessment of the safety and efficacy of combination therapy. Adolesc. Health, Med. & Ther. 2010; 1: 115–128.4.4. Lavanchy D. Evolving epidemiology of hepatitis C virus. Clin. microbial. infect. 2011; 17 (2): 107–115.5.5. Vajro P., Veropalumbo C., Maddaluno S., Salerno M., Parenti G., Pignata C. Treatment of children with chronic viral hepatitis: what is available and what is in store. World J. Pediatr. 2013; 9 (3): 212–220.6.6. WHO. Hepatitis C.7.7. URL:http://www.who.int/csr/disease/hepatitis/whocdscsrlyo2003/en/index1.html (available: 15.11.2010).8.8. Заболеваемость хроническими вирусными гепатитами детского населения в Российской Федерации за период c 2003–2011 гг. Под ред. А.А. Баранова, Л.С. Намазовой-Барановой и др. СПб: Ультра Принт. 2012. 46 с.9.9. Bortolotti F., Verucchi G., Cammà C., Cabibbo G., Zancan L., Indolfi G., Giacchino R., Marcellini M., Marazzi M.G., Barbera C., Maggiore G., Vajro P., Bartolacci S., Balli F., Maccabruni A., Guido M. Long-term course of chronic hepatitis C in children: from viral clearance to end-stage liver disease. Gastroenterology. 2008; 134 (7): 1900–1907.10.10. González-Peralta R.P., Langham M.R., Andres J.M., Mohan P., Colombani P.M., Alford M.K., Schwarz K.B. Hepatocellular carcinoma in 2 young adolescents with chronic hepatitis C. J. Pediatr. Gastroenterol. Nutr. 2009; 48 (5): 630–635.11.11. Indolfi G., Azzari C., Resti M. Perinatal Transmission of Hepatitis C Virus. J. Pediatr. 2013; 163 (6): 1549–1552.12.12. Indolfi G., Bartolini E., Resti M. Spontaneous clearance of hepatitis C virus in vertically infected children: any clue for treatment? Eur. J. Pediatr. 2011; 170 (12): 1621.13.13. Galoppo M., Galoppo C. Management of hepatitis C virus infection in childhood. Ann. Hepatol. 2010; 9 (1): 98–102.14.14. Mohan N., González-Peralta R.P., Fujisawa T., Chang M.H., Heller S., Jara P., Kelly D., Mieli-Vergani G., Shah U., Murray K.F. Chronic hepatitis C virus infection in children. J. Pediatr. Gastroenterol. Nutr. 2010; 50 (2): 123–131.15.15. Murakami J., Nagata I., Iitsuka T., Okamoto M., Kaji S., Hoshika T., Matsuda R., Kanzaki S., Shiraki K., Suyama A., Hino S. Risk factors for mother-to-child transmission of hepatitis C virus: Maternal high viral load and fetal exposure in the birth canal. Hepatol. Res. 2012; 42 (7): 648–657.16.16. Thomas S.L., Newell M.L., Peckham C.S., Ades A.E., Hall A.J. A review of hepatitis C virus (HCV) vertical transmission: risk of transmission to infants born to mothers with and without HCV viraemia or human immunodeficiency virus infection. Int. J. Epidemiol. 1998; 27 (1): 108–117.17.17. Zanetti A.R., Tanzi Е., Semprini А.Е. Hepatitis C in pregnancy and mother-to-infant transmission of HCV. Congenital and other related infectious disease of the newborn. Ed. I.K. Mushahwar. 2007. P. 153–171.18.18. Сенягина Н.Е., Лаврова А.Е., Зорин В.В., Галова Е.А. Факторы риска перинатальной передачи вирусного гепатита С. Медицинский альманах. 2011; 4 (17): 34–36.19.19. Pembrey L., Newel M.L., Tovo P.A. the EPHN Collaborators. The management of HCV infected pregnant women and their children. European Paediatric HCV Network. J. Hepatol. 2005; 43 (3): 515–525.20.20. Polywka S., Pembrey L., Tovo P., Newel M. Accuracy of HCV RNA PCR tests for diagnosis or exclusion of vertically acquired infection. J. Med. Virol. 2006; 78 (2): 305–310.21.21. Resti M., Bortolotti F., Azzari C., Giacchino R., Zancan L., Gussetti N., Vierucci A. Transmission of hepatitis C virus from infected mother to offspring during subsequent pregnancies. J. Pediatr. Gastroenterol. Nutr. 2000; 30 (5): 491–493.22.22. Boxall E., Baumann K., Price N., Sira J., Brown M., Kelly D. Discordant outcome of perinatal transmission of hepatitis C in twin pregnancies. J. Clin. Virol. 2007; 38 (2): 91–95.23.23. Inui A., Fujisawa T., Sogo T., Komatsu H., Isozaki A., Sekine I. Different outcomes of vertical transmission of hepatitis C virus in a twin pregnancy. J. Gastroenterol. Hepatol. 2002; 17 (5): 617–619.24.24. Poiraud S., Cohen J., Amiot X., Berkane N., Flahault A., Dussaix E. Mother-to-child transmission of hepatitis C virus: a case-control study of risk factors. The American Gastroenterological Association and Digestive Disease Week. Atlanta. 2001. Abstract № 1879.25.25. Kumar R.M., Shabul S. Role of breast feeding in transmission of hepatitis C virus to infants of HCV-infected mothers. J. Hepatol. 1998; 29 (2): 191–197.26.26. Polywka S., Schröter M., Feucht H.H., Zöllner B., Laufs R. Low risk of vertical transmission of hepatitis C virus by breast milk. Clin. Infect. Dis. 1999; 29 (5):1327–1329.27.27. Ghamar Chehreh M.E., Tabatabaei S.V., Khazanehdari S., Alavian SM. Effect of cesarean section on the risk of perinatal transmission of hepatitis C virus from HCV-RNA+/HIV-mothers: a meta-analysis. Arch. Gynecol Obstet. 2011; 283 (2): 255–260.28.28. Indolfi G., Resti M. Perinatal transmission of hepatitis C virus infection. J. Med. Virol. 2009; 81 (5): 836–843.29.29. Indolfi G., Nesi A., Resti M. Intrafamilial transmission of hepatitis C virus. J. Med. Virol. 2013; 85 (4): 608–614.30.30. Indolfi G., Bartolini E., Azzari C., Becciolini L., Moriondo M., de Martino M., Resti M. Intrafamilial transmission of hepatitis C virus: infection of the father predicts the risk of perinatal transmission. J. Med. Virol. 2008; 80 (11): 1907–1911.31.31. Bosi I., Ancora G., Mantovani W., Miniero R., Verucchi G., Attard L., Venturi V., Papa I., Sandri F., Dallacasa P., Salvioli G.P. HLA DR13 and HCV vertical infection. Pediatr. Res. 2002; 51 (6): 746–749.32.32. Bevilacqua E., Fabris A., Floreano P., Pembrey L., Newell M.L., Tovo P.A., Amoroso A. Genetic factors in mother-to-child transmission of HCV infection. Virology. 2009; 390 (1): 64–70.33.33. Martinetti M., Pacati I., Cuccia M., Badulli C., Pasi A., Salvanes-chi L., Minola E., De Silvestri A., Iannone A.M., Maccabruni A. Hierarchy of baby-linked immunogenetic risk factors in the vertical transmission of hepatitis C virus. Int. J. Immunopathol. Pharmacol. 2006; 19 (2): 369–378.34.34. Indolfi G., Mangone G., Calvo P.L., Bartolini E., Nebbia G., Calvo P.L., Moriondo M., Tovo P.-A., de Martino M., Azzari C., Resti M. Comparative Analysis of rs12979860 SNP of the IFNL3 Gene in Children with Hepatitis C and Ethnic Matched Controls Using 1000 Genomes Project Data. PLoS ONE. 2014; 9 (1): 85899.35.35. Indolfi G., Mangone G., Calvo P.L., Bartolini E., Regoli M., Serranti D., Calitri C., Tovo P. A., de Martino M., Azzari C., Resti M. Interleukin 28B rs12979860 Single-Nucleotide Polymorphism Predicts Spontaneous Clearance of Hepatitis C Virus in Children. J. Pediatr. Gastroenterol. Nutr. 2014; 58 (5): 666–668.36.36. Indolfi G., Sambrotta M., Moriondo M., Azzari C., Resti M. Genetic variation in interleukin-28B locus is associated with spontaneous clearance of HCV in children with non-1 viral genotype infection. J. Hepatology. 2011; 54 (4): 1490–1491.37.37. Ruiz-Extremera Á., Muñoz-Gámez JA., Salmerón-Ruiz MA., Muñoz de Rueda P., Quiles-Pérez R., Gila-Medina A., Casado J., Martín A.B., Sanjuan-Nuñez L., Carazo Á., Pavón E.J., Ocete-Hita E., León J., Salmerón J. Genetic Variation in IL28B with respect to Vertical Transmission of Hepatitis C Virus and Spontaneous Clearance in HCV Infected Children. J. Hepatology. 2011; 53 (6): 1830–1838.38.38. Saito T., Mizuno K., Katsumi T., Tomita K., Sato C., Okumoto K., Nishise Y., Watanabe H., Shao L., Ueno Y. Transmission of Hepatitis C Virus From a Mother to a Child Carrying IL28B Heterozygote rs8099917 Among Three Brothers: A Long-Term Follow Up. J. Med. Cases. 2014; 5 (4): 227–231.39.39. Shaker O.G., Nassar Y.H., Nour Z.A., El-Razki M. Single Nucleotide Polymorphisms of IL-10 and IL-28B as predictors to the response of interferon therapy in HCV genotype 4 infected children. J. Pediatr. Gastroenterol. Nutr. 2013; 57 (2): 155–160.40.40. Goodman Z.D., Makhlouf H.R., Liu L., Balistreri W., Gonzalez- Peralta RP., Haber B., Jonas M.M., Mohan P., Molleston J.P., Murray K.F., Narkewicz M.R., Rosenthal P., Smith L.J., Robuck P.R., Schwarz K.B. Pathology of chronic hepatitis C in children: liver biopsy findings in the Peds-C Trial. J. Hepatology. 2008; 47 (3): 836–843.41.41. Munir S., Saleem S., Idrees M., Tariq A., Butt S., Rauff B., Hussain A., Badar S., Naudhani M., Fatima Z., Ali M., Ali L., Akram M., Aftab M., Khubaib B., Awan Z. Hepatitis C treatment: current and future perspectives. Virol. J. 2010; 7: 296.42.42. Nydegger A., Srivastava A., Wake M., Smith A.L., Hardikar W. Health-related quality of life in children with hepatitis C acquired in the first year of life. J. Gastroenterol. Hepatol. 2008; 23 (2): 226–230.43.43. Rodrigue J.R., Balistreri W., Haber B., Jonas M.M., Mohan P., Molleston J.P., Murray K.F., Narkewicz M.R., Rosenthal P., Smith L.J., Schwarz K.B., Robuck P., Barton B., González-Peralta R.P. Impact of hepatitis C virus infection on children and their caregivers: quality of life, cognitive, and emotional outcomes. J. Pediatr. Gastroenterol. Nutr. 2009; 48 (3): 341–347.44.44. Ward J.W., Lok A.S., Thomas D.L., El-Serag H.B., Kim W.R. Report on a single topic conference on «chronic viral hepatitis-strategies to improve effectiveness of screening and treatment». J. Hepatology. 2012; 55 (1): 307–315.45.45. Wirth S., Kelly D., Sokal E., Socha P., Mieli-Vergani G., Dhawan A., Lacaille F., Saint Raymond A., Olivier S., Taminiau J. Guidance for clinical trials for children and adolescents with chronic hepatitis C. J. Pediatr. Gastroenterol. Nutr. 2011; 52 (2): 233–237.46.46. Mack C.L., Gonzalez–Peralta R.P., Gupta N., Leung D., Narkewicz MR., Roberts E.A., Rosenthal P., Schwarz K.B. NASPGHAN practice guidelines: Diagnosis and management of hepatitis C infection in infants, children, and adolescents. J. Pediatr. Gastroenterol. Nutr. 2012; 54 (6): 838–855.47.47. Druyts E., Thorlund K., Wu P., Kanters S., Yaya S., Cooper C.L., Mills E.J. Efficacy and safety of pegylated interferon alfa-2a or alfa-2b plus ribavirin for the treatment of chronic hepatitis C in children and adolescents: a systematic review and meta-analysis. Clin. Infect. Dis. 2013; 56 (7): 961–967.48.48. Hu J., Doucette K., Hartling L., Tjosvold L., Robinson J. Treatment of hepatitis C in children: a systematic review. PLoS One. 2010; 5 (7): 11542.49.49. Потапов А.С., Пахомовская Н.Л., Волынец Г.В., Четкина Т.С. Интерферонотерапия хронического вирусного гепатита С у детей. Фарматека. 2009; 13: 67–71.50.50. Волынец Г.В., Потапов А.С., Пахомовская Н.Л. Повышение эффективности интерферонотерапии хронического гепатита С у детей с помощью рекомбинантного интерлейкина-2 (рон-колейкина). Российский педиатрический журнал. 2011; 6: 9–14.51.51. Delgado-Borrego A. Treating hepatitis C: are children the same as adults? Gastroenterology. 2011; 140 (2): 389–392.52.52. Sokal E.M., Bourgois A., Stéphenne X., Silveira T., Porta G., Gardovska D., Fischler B., Kelly D. Peginterferon alfa–2a plus ribavirin for chronic hepatitis C virus infection in children and adolescents. J. Hepatology. 2010; 52 (6): 827–831.53.53. Swain M.G., Lai M.Y., Shiffman M.L., Cooksley W.G., Zeuzem S., Dieterich D.T., Abergel A., Pessôa M.G., Lin A., Tietz A., Con-nell E.V., Diago M. A sustained virologic response is durable in patients with chronic hepatitis C treated with peginterferon alfa-2a and ribavirin. Gastroenterology. 2010; 139 (5): 1593–1601.54.54. Craxi A., Koutsounas S., Ogurtsov P., Chemello L., Maticic M., Torras J., Diago M., Tartaglione MT., Witthoeft T., Yu X., Faruqi R., Chaudhri E., Pedicone L.D., Zuckerman E. Peginterferon alfa-2b plus weightbased ribavirin for 24 weeks in patients with chronic hepatitis C virus genotype 1 with low viral load who achieve rapid viral response. J. Viral Hepat. 2012; 19 (2): 120–125.55.55. Tsubota A., Fujise K., Namiki Y., Tada N. Peginterferon and ribavirin treatment for hepatitis C virus infection. World J. Gastroenterol. 2011; 17: 419–432.56.56. Thompson A.J., Muir A.J., Sulkowski M.S., Ge D., Fellay J., Shianna K.V., Urban T., Afdhal N.H., Jacobson I.M., Esteban R., Poordad F., Lawitz E.J., McCone J., Shiffman M.L., Galler G.W., Lee W.M., Reindollar R., King J.W., Kwo P.Y., Ghalib R.H., Freilich B., Nyberg L.M., Zeuzem S., Poynard T., Vock D.M., Pieper K.S., Patel K., Tillmann H.L., Noviello S., Koury K., Pedicone L.D., Brass C.A., Albrecht J.K., Goldstein D.B., McHutchison J.G. Interleukin-28B polymorphism improves viral kinetics and is the strongest pretreatment predictor of sustained virologic response in genotype 1 hepatitis C virus. Gastroenterology. 2010; 139 (1): 120–129.57.57. Лопаткина Т.Н. Индивидуализированная противовирусная терапия хронического вирусного гепатита С сегодня. Клиническая фармакология и терапия. 2011; 4: 15–20.58.58. Скворцова Т.А., Волынец Г.В., Семикина Е.Л. Персонализированный подход к лечению хронического гепатита С у детей. Педиатрическая фармакология. 2014; 2: 66–71.59.59. Rauch A., Kutalik Z., Descombes P., Cai T., Di Iulio J., Mueller T., Bochud M., Battegay M., Bernasconi E., Borovicka J., Colombo S., Cerny A., Dufour JF., Furrer H., Günthard HF, Heim M., Hirschel B., Malinverni R., Moradpour D., Müllhaupt B., Witteck A., Beckmann J.S., Berg T., Bergmann S., Negro F., Telenti A., Bochud P.Y. Genetic variation in IL28B is associated with chronic hepatitis C and treatment failure: a genome-wide association study. Gastroenterology. 2010; 138 (4): 1338–1345.60.60. Suppiah V., Moldovan M., Ahlenstiel G., Berg T., Weltman M., Abate M.L., Bassendine M., Spengler U., Dore G.J., Powell E., Riordan S., Sheridan D., Smedile A., Fragomeli V., Müller T., Bahlo M., Stewart G.J., Booth D.R., George J. IL28B is associated with response to chronic hepatitis C interferon-alpha and ribavirin therapy. Nat. Genet. 2009; 41 (10): 1100–1104.61.61. Tanaka Y., Nishida N., Sugiyama M., Kurosaki M., Matsuura K., Sakamoto N., Nakagawa M., Korenaga M., Hino K., Hige S., Ito Y., Mita E., Tanaka E., Mochida S., Murawaki Y., Honda M., Sakai A., Hiasa Y., Nishiguchi S., Koike A., Sakaida I., Imamura M., Ito K., Yano K., Masaki N., Sugauchi F., Izumi N., Tokunaga K., Mizokami M. Genome–wide association of IL28B with response to pegylated interferon-alpha and ribavirin therapy for chronic hepatitis C. Nat. Genet. 2009; 41 (10): 1105–1109.62.62. Ge D., Fellay J., Thompson A.J., Simon J.S., Shianna K.V., Urban T.J., Heinzen E.L., Qiu P., Bertelsen A.H., Muir A.J., Sulkowski M., McHutchison J.G., Goldstein D.B. Genetic variation in IL28B predicts hepatitis C treatment-induced viral clearance. Nature. 2009; 461 (7262): 399–401.63.63. Nelson D.R., Rustgi V., Balan V., Sulkowski M.S., Davis G.L., Muir A.J., Lambiase L.R., Dickson R.C., Weisner R.H., Fiscella M., Cronin P.W., Pulkstenis E., McHutchison J.G., Subramanian G.M. Safety and antiviral activity of albinterferon alfa–2b in prior interferon nonresponders with chronic hepatitis C. Clin. Gastroenterol. Hepatol. 2009: 7 (2): 212–218.64.64. Krastev S., Stoynov R., Balabanska E,. Lawitz Z., Younossi R., Ghalib E., Zuckerman R., Safadi R., Tur-Kaspa N., Assy Y., Lurie L. Q2 week controlled-release-interferon-alpha2B +ribavirin reduces flu-like symptoms >50% and provides equivalent efficacy in comparison to weekly pegylated-interferonalpha2B + ribavirin in treatment-naive-Genotype-1-chronichepatitis–C: results from empower, a randomized-open-label-12- weekcomparison in 133 patients. J. Hepatology. 2010; 52: 467.65.65. Lawitz E., Younossi Z., Mehra R., Rigney A., Krastev Z., Tchernev K., Takov D., Long W.A. 444 SVR for controlled-release interferon alpha-2B (CR2B) +ribavirin compared to pegylated interferon alpha-2B (PEG2B) + ribavirin in treatment-naive Genotype-1 (G1) Hepatitis C: final results from select-2. J. Hepatology. 2011; 54: 180–181.66.66. Lee L.Y., Tong C.Y., Wong T., Wilkinson M. New therapies for chronic hepatitis C infection: a systematic review of evidence from clinical trials. Int. J. Clin. Pract. 2012; 66 (4): 342–355.67.67. Jacobson I.M., McHutchison J.G., Dusheiko G., Di Bisceglie A.M., Reddy K.R., Bzowej N.H., Marcellin P., Muir A.J., Ferenci P., Flisiak R., George J., Rizzetto M., Shouval D., Sola R., Terg R.A., Yoshida E.M., Adda N., Bengtsson L., Sankoh A.J., Kieffer T.L., George S., Kauffman R.S., Zeuzem S. ADVANCE Study Team. Telaprevir for previously untreated chronic hepatitis C virus infection. N. Engl. J. Med. 2011; 364 (25): 2405–2416.68.68. Kwong A.D., Kauffman R.S., Hurter P., Mueller P. Discovery and development of telaprevir: an NS3-4A protease inhibitor for treating genotype 1 chronic hepatitis C virus. Nat. Biotechnol. 2011; 29 (11): 993–1003.69.69. Marcellin P., Forns X., Goeser T., Ferenci P., Nevens F., Carosi G., Drenth J.P., Serfaty L., De Backer K., Van Heeswijk R., Luo D., Picchio G., Beumont M. Telaprevir is effective given every 8 or 12 hours with ribavirin and peginterferon alfa-2a or -2b to patients with chronic hepatitis C. Gastroenterology. 2011; 140 (2): 459–468.70.70. Sherman K.E., Flamm S.L., Afdhal N.H., Nelson D.R., Sulkow-ski M.S., Everson G.T., Fried M.W., Adler M., Reesink H.W., Martin M., Sankoh A.J., Adda N., Kauffman R.S., George S., Wright C.I., Poordad F. Illuminate Study Team. Response-guided telaprevir combination treatment for hepatitis C virus infection. N. Engl. J. Med. 2011; 365 (11): 1014–1024.71.71. Zeuzem S., Andreone P., Pol S., Lawitz E., Diago M., Roberts S., Focaccia R., Younossi Z., Foster G.R., Horban A., Ferenci P., Nevens F., Müllhaupt B., Pockros P., Terg R., Shouval D., van Hoek B., Weiland O., Van Heeswijk R., De Meyer S., Luo D., Boogaerts G., Polo R., Picchio G., Beumont M. Telaprevir for retreatment of HCV infection. N. Engl. J. Med. 2011; 364 (25): 2417–2428.72.72. Bacon B.R., Gordon S.C., Lawitz E., Marcellin P., Vierling J.M., Zeuzem S., Poordad F., Goodman Z.D., Sings H.L., Boparai N., Burroughs M., Brass C.A., Albrecht J.K., Esteban R. HCV RESPOND-2 Investigators. Boceprevir for previously treated chronic HCV genotype 1 infection. N. Engl. J. Med. 2011; 364 (13): 1207–1217.73.73. Kwo P.Y., Lawitz E.J., McCone J., Schiff E.R., Vierling J.M., Pound D., Davis M.N., Galati J.S., Gordon S.C., Ravendhran N., Rossaro L., Anderson F.H., Jacobson I.M., Rubin R., Koury K., Pedicone L.D., Brass C.A., Chaudhri E., Albrecht J.K. SPRINT-1 investigators. Efficacy of boceprevir, an NS3 protease inhibitor, in combination with peginterferon alfa–2b and ribavirin in treatmentnaive patients with genotype 1 hepatitis C infection (SPRINT-1): an open-label, randomised, multicentre phase 2 trial. Lancet. 2010; 376 (9742): 705–716.74.74. Poordad F., Mccone J., Bacon B., Bruno S., Manns M.P., Sulkowski M.S., Jacobson I.M., Reddy K.R., Goodman Z.D., Boparai N., DiNubile M.J., Sniukiene V., Brass C.A., Albrecht J.K., Bronowicki J.P. SPRINT-2 Investigators. Boceprevir for untreated chronic HCV genotype 1 infection. N. Engl. J. Med. 2011; 364 (13): 1195–1206.75.75. Gane E.J., Stedman C.A., Hyland R.H., Ding X., Svarovskaia E., Symonds W.T., Hindes R.G., Berrey M.M. Nucleotide polymerase inhibitor sofosbuvir plus ribavirin for hepatitis C. N. Engl. J. Med. 2013; 368 (1): 34–44.76.76. Jacobson I.M., Gordon S.C., Kowdley K.V., Yoshida E.M., Rodriguez-Torres M., Sulkowski M.S., Shiffman M.L., Lawitz E., Everson G., Bennett M., Schiff E., Al-Assi M.T., Subramanian G.M., An D., Lin M., McNally J., Brainard D., Symonds W.T., McHutchison J.G., Patel K., Feld J., Pianko S., Nelson D.R. POSITRON Study. FUSION Study. Sofosbuvir for hepatitis C genotype 2 or 3 in patients without treatment options. N. Engl. J. Med. 2013; 368 (20): 1867–1877.77.77. Lawitz E., Mangia A., Wyles D., Rodriguez-Torres M., Hassanein T., Gordon S.C., Schultz M., Davis M.N., Kayali Z., Reddy K.R., Jacobson I.M., Kowdley K.V., Nyberg L., Subramanian G.M., Hyland R.H., Arterburn S., Jiang D., McNally J., Brainard D., Symonds W.T., McHutchison J.G., Sheikh A.M., Younossi Z., Gane E.J. Sofosbuvir for previously untreated chronic hepatitis C infection. N. Engl. J. Med. 2013; 368 (20): 1878–1887.78.78. Lapierre P., Troesc M., Alvarez F., Soudeyns H. Structural basis for broad neutralization of hepatitis C virus quasispecies. PloS One. 2011; 6 (10): 26981.79.79. Torresi J., Johnson D., Wedemeyer H. Progress in the development of preventive and therapeutic vaccines for hepatitis C virus. J. Hepatol. 2011; 54 (6): 1273–1285.