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Российский вестник перинатологии и педиатрии

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Современный взгляд на лечение хронического гепатита С у детей и подростков

https://doi.org/10.21508/1027-4065-2019-64-6-11-19

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Аннотация

Цель статьи – обобщающий обзор подходов к лечению инфекции, вызванной вирусом гепатита С (HCV), у детей и подростков. Статья посвящена вопросам, затрагивающим показания, противопоказания и оптимальные схемы лечения у детей и подростков с хронической HCV-инфекцией.

Во всем мире 13,2 (11,5–21,2) млн детей в возрасте от 1 до 15 лет инфицированы HCV. У детей, как правило, хроническая HCV-инфекция более вялотекущая, чем у взрослых; внепеченочные проявления преимущественно в виде субклинического гипотиреоза и аутоиммунного тиреоидита встречаются соответственно в 11 и 5,6% случаев. Риск развития цирроза печени у детей с хронической HCV-инфекцией составляет от 1 до 4%, в то время как мостовидный фиброз и тяжелое воспаление печени описаны примерно у 15%. В статье рассматриваются вопросы терапии: цели, конечные точки, показания, противопоказания и оптимальный режим лечения у детей с хронической HCV-инфекцией. Представлены рекомендации, сформулированные Европейским обществом детских гастроэнтерологов, гепатологов и нутрициологов (ESPGHAN).

Заключение. Хроническая HCV-инфекция у детей в целом протекает в доброкачественной форме, однако лечение заболевания требуется для достижения успеха в деле ликвидации гепатита С.

Об авторе

Г. В. Волынец
ФГАОУ ВО «Российский национальный исследовательский медицинский университет им. Н.И. Пирогова» Минздрава России; ОСП «Научно-исследовательский клинический институт педиатрии им. академика Ю.Е. Вельтищева» ФГАОУ ВО РНИМУ им. Н.И. Пирогова Минздрава России
Россия

Волынец Галина Васильевна – д.м.н., гл. науч. сотр. отдела гастроэнтерологии Научно-исследовательского клинического института педиатрии им. академика Ю.Е. Вельтищева

Москва



Список литературы

1. Cacoub P., Gragnani L., Comarmond C., Zignego A.L. Extrahepatic manifestations of chronic hepatitis C virus infection. Dig Liver Dis 2014; 46(5): 165–173. DOI: 10.1016/j.dld.2014.10.005

2. Kanto T., Hayashi N. Immunopathogenesis of hepatitis C virus infection: multifaceted strategies subverting innate and adaptive immunity. Intern Med 2006; 45(4): 183–191. DOI:10.2169/internalmedicine.45.1530

3. Семенов А.В., Арсентьева Н.А., Елезов Д.С., Кондратьев И.В., Тотольян А.А. Особенности популяционного состава CXCRS-положительных лимфоцитов периферической крови больных хроническим гепатитом С. Журнал микробиологии, эпидемиологии и иммунобиологии 2013; 6: 69–76.

4. Cotte L., Cua E., Reynes J., Raffi F., Rey D., Delobel P., et al. Hepatitis C virus incidence in HIV-infected and in preexposure prophylaxis (PrEP)-using men having sex with men. Liver Int 2018; published online June 30. DOI: 10.1111/liv.13922

5. Platt L., Easterbrook P., Gower E., McDonald B., Sabin K., McGowan C. et al. Prevalence and burden of HCV co-infection in people living with HIV: a global systematic review and meta-analysis. Lancet Infect Dis 2016; 16(7): 797–808. DOI:10.1016/S1473-3099(15)00485-5

6. van de Laar T., Pybus O., Bruisten S., Brown D., Nelson M., Bhagani S. et al. Evidence of a large, international network of HCV transmission in HIV-positive men who have sex with men. Gastroenterol 2009; 136(5): 1609–1617. DOI:10.1053/j.gastro.2009.02.006

7. Zibbell J.E., Iqbal K., Patel R.C., Suryaprasad A., Sanders K.J., Moore-Moravian L. et al. Centers for Disease Control and Prevention (CDC). Increases in hepatitis C virus infection related to injection drug use among persons aged ≤30 years – Kentucky, Tennessee, Virginia, and West Virginia, 2006–2012. MMWR Morb Mortal Wkly Rep 2015; 64(17): 453–458.

8. WHO. Global hepatitis report 2017. World Health Organization. https://apps.who.int/iris/handle/10665/255016

9. Thursz M., Fontanet A. HCV transmission in industrialized countries and resource-constrained areas. Nat Rev Gastroenterol Hepatol 2014; 11(1): 28–35. DOI: 10.1038/nrgastro.2013.179

10. Indolfi G., Azzari C., Resti M. Perinatal transmission of hepatitis C virus. J Pediatr 2013; 163(6): 1549–1552.e1. DOI:10.1016/j.jpeds.2013.06.077

11. Benova L., Mohamoud Y.A., Calvert C., Abu-Raddad L.J. Vertical transmission of hepatitis C virus: systematic review and meta-analysis. Clin Infect Dis 2014; 59(6): 765–73. DOI:10.1093/cid/ciu447

12. European Paediatric Hepatitis C Virus Network. A significant sex–but not elective cesarean section–effect on mother-tochild transmission of hepatitis C virus infection. J Infect Dis 2005; 192: 1872–1879.

13. Indolfi G., Nesi A., Resti M. Intrafamilial transmission of hepatitis C virus. J Med Virol 2013; 85(4): 608–614. DOI:10.1002/jmv.23522

14. Jafari S., Copes R., Baharlou S., Etminan M., Buxton J. Tattooing and the risk of transmission of hepatitis C: a systematic review and meta-analysis. Int J Infect Dis 2010; 14(11): e928–40. DOI: 10.1016/j.ijid.2010.03.019

15. Global Burden of Disease Study 2013 Collaborators. Glo al, regional, and national incidence, prevalence, and years lived with disability for 301 acute and chronic diseases and injuries in 188 countries, 1990–2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet 2015; 386(9995): 743–800. DOI: 10.1016/S0140-6736(15)60692-4

16. El-Sayed M.H., Razavi H. Global estimate of HCV infection in the pediatric and adolescent population. J Hepatol 2015; 62(2): 831–832. DOI: 10.1016/S0168-8278(15)31458-6

17. Razavi H., El-Sayed M. Updated global estimate of HCV infection in the pediatric population. 2016. http://cdafound.org/content/Downloads/Pediatric%20Prevalence%20161201.pdf (accessed March 31, 2019).

18. Delgado-Borrego A., Smith L., Jonas M.M., Hall C.A., Negre B., Jordan S.H. et al. Expected and actual case ascertainment and treatment rates for children infected with hepatitis C in Florida and the United States: epidemiologic evidence from statewide and nationwide surveys. J Pediatr 2012; 161(5): 915–921. DOI: 10.1016/j.jpeds.2012.05.002

19. Koneru A., Nelson N., Hariri S., Canary L., Sanders K.J., Maxwell J.F. et al. Increased Hepatitis C Virus (HCV) Detection in Women of Childbearing Age and Potential Risk for Vertical Transmission – United States and Kentucky, 2011–2014. MMWR Morb Mortal Wkly Rep 2016; 65(28): 705–710.

20. United Nations. Transforming our world: the 2030 agenda for sustainable development. New York: United Nations, 2015. https://www.preventionweb.net/go/45418

21. Bortolotti F., Verucchi G., Camma` C., Cabibo G., Zancan L., Indolfi G. et al. Long-Term Course of Chronic Hepatitis C in Children: From Viral Clearance to End-Stage Liver Disease. Gastroenterol 2008; 134: 1900–1907. DOI: 10.1053/j.gastro.2008.02.082

22. Resti M., Jara P., Hierro L., Azzari C., Giacchino R., Zuin G. et al. Clinical features and progression of perinatally acquired hepatitis C virus infection. J Med Virol 2003; 70: 373–377. DOI: 10.1002/jmv.10405

23. Network EPHCV. Three broad modalities in the natural history of vertically acquired hepatitis C virus infection. Clin Infect Dis 2005; 41: 45–51. DOI: 10.1086/430601

24. Garazzino S., Calitri C., Versace A., Alfarano A., Scolfaro C., Bertaina C. et al. Natural history of vertically acquired HCV infection and associated autoimmune phenomena. Eur J Pediatr 2014; 173(8): 1025–1031. DOI: 10.1007/s00431-014-2286-6

25. Jara P., Resti M., Hierro L., Giacchino R., Barbera C., Zancan L. et al. Chronic hepatitis C virus infection in childhood: clinical patterns and evolution in 224 white children. Clin Infect Dis 2003; 36: 275–280. DOI: 10.1086/345908

26. Cacoub P., Gragnani L., Comarmond C., Zignego A.L. Extrahepatic manifestations of chronic hepatitis C virus infection. Dig Liver Dis 2014; 46(5): 165–173. DOI: 10.1016/j.dld.2014.10.005

27. Indolfi G., Stagi S., Bartolini E., Salti R., de Martino M., Azzari C., Resti M. Thyroid function and anti-thyroid autoantibodies in untreated children with vertically acquired chronic hepatitis C virus infection. Clin Endocrinol (Oxf) 2008; 68: 117–121. DOI: 10.1111/j.1365-2265.2007.03009.x

28. Goodman Z.D., Makhlouf H.R., Liu L., Balistreri W., Gonzalez-Peralta R.P., Haber B. et al. Pathology of chronic hepatitis C in children: liver biopsy findings in the Peds-C Trial. Hepatology 2008; 47: 836–843. DOI: 10.1002/hep.22094

29. Harris H.E., Mieli-Vergani G., Kelly D., Davison S., Gibb D.M., Ramsay M.E.; HCV National Register Steering Group. A national sample of individuals who acquired hepatitis C virus infections in childhood or adolescence: risk factors for advanced disease. J Pediatr Gastroenterol Nutr 2007; 45(3): 335–341. DOI: 10.1097/MPG.0b013e3180dc9337

30. Iorio R., Giannattasio A., Sepe A., Terracciano L.M., Vecchione R., Vegnente A. Chronic hepatitis C in childhood: an 18-year experience. Clin Infect Dis 2005; 41(10): 1431–7. DOI:10.1086/497141

31. Mohan P., Barton B.A., Narkewicz M.R., Molleston J.P., Gonzalez-Peralta R.P., Rosenthal P. et al. Evaluating progression of liver disease from repeat liver biopsies in children with chronic hepatitis C – a retrospective study. Hepatology 2013; 58(5): 1580–1586. DOI: 10.1002/hep.26519

32. González-Peralta R.P., Langham M.R.Jr., 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. DOI: 10.1097/MPG.0b013e318170af04

33. Malik S., Dekio F., Wen J.W. Liver transplantation in a child with multifocal hepatocellular carcinoma hepatitis C and management of post-transplant viral recurrence using boceprevir. Pediatr Transplant 2014; 18(2): E64–68. DOI:10.1111/petr.12223

34. Modin L., Arshad A., Wilkes B., Benselin J., Lloyd C., Irving W.L., Kelly D.A. Epidemiology and natural history of hepatitis C virus infection among children and young people. J Hepatol 2019; 70(3): 371–378. DOI: 10.1016/j.jhep.2018.11.013

35. EASL Recommendations on Treatment of Hepatitis C 2016. J Hepatol 2017; 66(1): 153–194. DOI: 10.1016/j.jhep.2016.09.001

36. Omata M., Kanda T., Wei L., Yu M.L., Chuang W.L., Ibrahim A. et al. APASL consensus statements and recommendation on treatment of hepatitis C. Hepatol Int 2016; 10(5): 702–726. DOI: 10.1007/s12072-016-9717-6

37. Wirth S., Rosenthal P., Gonzalez-Peralta R.P., Jonas M.M., Balistreri W.F., Lin C.H. et al. Sofosbuvir and ribavirin in adolescents 12–17 years old with hepatitis C virus genotype 2 or 3 infection. Hepatology 2017; 66(4): 1102–1110. DOI:10.1002/hep.29278

38. Younossi Z.M., Stepanova M., Schwarz K.B., Wirth S., Rosenthal P., Gonzalez-Peralta R. et al. Quality of life in adolescents with hepatitis C treated with sofosbuvir and ribavirin. J Viral Hepat 2018; 25(4): 354–362. DOI: 10.1111/jvh.12830

39. Younossi Z.M., Stepanova M., Balistreri W., Schwarz K., Murray K.F., Rosenthal P. et al. Health-related Quality of Life in Adolescent Patients With Hepatitis C Genotype 1 Treated With Sofosbuvir and Ledipasvir. J Pediatr Gastroenterol Nutr 2018; 66(1): 112–116. DOI: 10.1097/MPG.0000000000001754

40. Balistreri W.F., Murray K.F., Rosenthal P., Bansal S., Lin C.H., Kersey K. et al. The safety and effectiveness of ledipasvir-sofosbuvir in adolescents 12–17 years old with hepatitis C virus genotype 1 infection. Hepatology 2017; 66(2): 371–378. DOI: 10.1002/hep.28995

41. AASLD-IDSA HCV Guidance Panel. Hepatitis C Guidance 2018 Update: AASLD-IDSA Recommendations for Testing, Managing, and Treating Hepatitis C Virus Infection. Clin Infect Dis 2018; 67(10): 1477–1492. DOI: 10.1093/cid/ciy585

42. European Association for the Study of the Liver. EASL recommendations on treatment of hepatitis C 2018. J Hepatol 2018; 69(2): 461–511. DOI: 10.1016/j.jhep.2018.03.026

43. WHO. Guidelines for the care and treatment of persons diagnosed with chronic hepatitis C virus infection. Geneva: World Health Organization, 2018; 108.

44. Indolfi G., Hierro L., Dezsofi A., Jahnel J., Debray D., Hadzic N. et al. Treatment of Chronic Hepatitis C Virus Infection in Children: A Position Paper by the Hepatology Committee of European Society of Paediatric Gastroenterology, Hepatology and Nutrition. J Pediatr Gastroenterol Nutr 2018; 66(3): 505–515. DOI: 10.1097/MPG.0000000000001872

45. El-Khayat H.R., Kamal E.M., El-Sayed M.H., El-Shabrawi M., Ayoub H., RizK A. et al. The effectiveness and safety of ledipasvir plus sofosbuvir in adolescents with chronic hepatitis C virus genotype 4 infection: a real-world experience. Aliment Pharmacol Ther 2018; 47(6): 838–844. DOI: 10.1111/apt.14502

46. El-Karaksy H., Mogahed E.A., Abdullatif H., Ghobrial C., El-Raziky M.S., El-Koofy N. et al. Sustained Viral Response in Genotype 4 Chronic Hepatitis C Virus-infected Children and Adolescents Treated With Sofosbuvir/Ledipasvir. J Pediatr Gastroenterol Nutr 2018; 67(5): 626–630. DOI: 10.1097/MPG.0000000000002101

47. Jonas M.M., Squires R.H., Rhee S.M., Lin C.W., Bessho K., Feiterna-Sperling C. et al. Pharmacokinetics, Safety, and Efficacy of Glecaprevir/Pibrentasvir in Pediatric Patients with Genotypes 1–6 Chronic HCV Infection: Part 1 of the Dora Study. Hepatology 2018; 68(suppl): 1347A–1348A.

48. Leung D.H., Wirth S., Yao B.B., Viani R.M., Gonzalez-Peralta R.P., Jonas M.M. et al. Ombitasvir/Paritaprevir/Ritonavir With or Without Dasabuvir and With or Without Ribavirin for Adolescents With HCV Genotype 1 or 4. Hepatol Commun 2018; 2(11): 1311–1319. DOI: 10.1002/hep4.1250

49. El-Sayed M., Hassany M., Asem N. A pilot study for safety and efficacy of 12 weeks sofosbuvir plus daclatasvir with or without ribavirin in egyptian adolescents with chronic hepatitis C virus Infection. J Hepatol 2017; 66(suppl): 178. DOI:10.1016/S0168-8278(17)30642-6

50. El-Shabrawi M.H., Abdo A.M., El-Khayat H.R., Yakoot M. Shortened 8 Weeks Course of Dual Sofosbuvir/Daclatasvir Therapy in Adolescent Patients, With Chronic Hepatitis C Infection. J Pediatr Gastroenterol Nutr 2018; 66(3): 425–427. DOI: 10.1097/MPG.0000000000001838

51. Yakoot M., El-Shabrawi M.H., AbdElgawad M.M., Mahfouz A.A., Helmy S., Abdo A.M., El-Khayat H.R. Dual Sofosbuvir/Daclatasvir Therapy in Adolescent Patients With Chronic Hepatitis C Infection. J Pediatr Gastroenterol Nutr 2018; 67(1): 86–89. DOI: 10.1097/MPG.0000000000001968

52. Al Ali J., Owayed S., Al-Qabandi W., Husain K., Hasan F. Pegylated interferon alfa-2b plus ribavirin for the treatment of chronic hepatitis C genotype 4 in adolescents. Ann Hepatol 2010; 9(2): 156–160.

53. Turkova A., Giacomet V., Goetghebuer T., Miloenko M., Nicolini L.A., Noguera-Julian A. et al. HCV treatment in children and young adults with HIV/HCV co-infection in Europe. J Virus Erad 2015; 1(3): 179–184.

54. 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. DOI: 10.1093/cid/cis1031

55. Mack C.L., Gonzalez-Peralta R.P., Gupta N., Leung D., Narkewicz M.R., Roberts E.A. et al. NASPGHAN practice guidelines: Diagnosis and management of hepatitis C infection in infants, children, and adolescents. J Pediatr Gastroenterol Nutr 2012; 54(6): 838–855. DOI: 10.1097/MPG.0b013e318258328d

56. Rosenthal P., Schwarz K.B., Gonzalez-Peralta R.P., Lin C.H., Kelly D.A., Nightingale S. et al. Sofosbuvir and Ribavirin Therapy for Children 3 to <12 Years Old With Hepatitis C Virus Genotype 2 or 3 Infection. Hepatology. 2019 Jun 20. DOI: 10.1002/hep.30821

57. Murray K.F., Balistreri W.F., Bansal S., Whitworth S., Evans H.M., Gonzalez-Peralta R.P. et al. Safety and Efficacy of Ledipasvir-Sofosbuvir With or Without Ribavirin for Chronic Hepatitis C in Children Ages 6–11. Hepatology 2018; 68(6): 2158–2166. DOI: 10.1002/hep.30123

58. Garrison K.L., Mathias A., Kersey K., Kanwar B., Ni L., Jain A. et al. Pharmacokinetics of once-daily Sofosbuvir and Ledipasvir/Sofosbuvir in HCV-infected pediatrics aged 6 to <12 years old. Hepatology 2016; 64 (suppl):436A.

59. El-Shabrawi M.H.F., Kamal N.M., El-Khayat H.R., Kamal E.M., AbdElgawad M.M., Yakoot M. A pilot single arm observational study of sofosbuvir/ledipasvir (200 + 45 mg) in 6to 12-year old children. Aliment Pharmacol Ther 2018; 47(12): 1699–1704. DOI: 10.1111/apt.14677


Для цитирования:


Волынец Г.В. Современный взгляд на лечение хронического гепатита С у детей и подростков. Российский вестник перинатологии и педиатрии. 2019;64(6):11-19. https://doi.org/10.21508/1027-4065-2019-64-6-11-19

For citation:


Volynets G.V. A modern view on the treatment of chronic hepatitis C in children and adolescents. Rossiyskiy Vestnik Perinatologii i Pediatrii (Russian Bulletin of Perinatology and Pediatrics). 2019;64(6):11-19. (In Russ.) https://doi.org/10.21508/1027-4065-2019-64-6-11-19

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