nidНефрология и диализNephrology and Dialysis1680-44222618-9801Российское диализное общество10.28996/2618-9801-2019-2-191-198nid-263Research ArticleОРИГИНАЛЬНЫЕ СТАТЬИORIGINAL ARTICLESВозможности современной противовирусной терапии хронической HCV-инфекции у реципиентов почечного трансплантатаAntiviral therapy of chronic HCV infection in kidney transplant recipientЗубкинМ. Л.ZubkinM. L.m-zubkin@yandex.ruКимИ. Г.KimI. G.noemail@neicon.ruАришеваО. С.ArishevaO. S.noemail@neicon.ruТомилинаН. А.TomilinaN. A.noemail@neicon.ruЧервинкоВ. И.ChervinkoV. I.noemail@neicon.ruСтоляревичЕ. С.StolyarevichE. S.noemail@neicon.ruАртюхинаЛ. Ю.ArtyuhinaL. Y.noemail@neicon.ruОстровскаяИ. В.OstrovskayaI. V.noemail@neicon.ruФроловаН. Ф.FrolovaN. F.noemail@neicon.ruСемененкоТ. А.SemenenkoT. A.noemail@neicon.ruКрюковЕ. В.KryukovE. V.noemail@neicon.ruФБУН Московский НИИ эпидемиологии и микробиологии им. Г.Н. Габричевского Роспотребнадзора; Филиал Военно-медицинской академии им. С.М. КироваРоссияG.N. Gabrichevsky Research Institute for Epidemiology and Microbiology; The Branch of the S.M. Kirov Military Medical AcademyRussian FederationФБУН Московский НИИ эпидемиологии и микробиологии им. Г.Н. Габричевского Роспотребнадзора; ГБУЗ "ГКБ № 52 Департамента здравоохранения г. Москвы"РоссияG.N. Gabrichevsky Research Institute for Epidemiology and Microbiology; Moscow City Nephrology Center, Moscow City Hospital 52Russian FederationФГАОУВО "Российский университет дружбы народов"РоссияRUDN UniversityRussian FederationГБУЗ "ГКБ № 52 Департамента здравоохранения г. Москвы"; ФПДО ФГБУ ФГОУ "Московский государственный медико-стоматологический университет им. А.И. Евдокимова"РоссияMoscow City Nephrology Center, Moscow City Hospital 52; A.I. Evdokimov Moscow State University of Medicine and DentistryRussian FederationФилиал Военно-медицинской академии им. С.М. КироваРоссияThe Branch of the S.M. Kirov Military Medical AcademyRussian FederationГБУЗ "ГКБ № 52 Департамента здравоохранения г. Москвы"РоссияMoscow City Nephrology Center, Moscow City Hospital 52Russian FederationФГБУ "НИЦЭМ им. Н.Ф. Гамалеи" Минздрава РоссииРоссияN.F. Gamaleya Federal Research Center for Epidemiology & MicrobiologyRussian FederationФГБУ Главный военный клинический госпиталь им. Н.Н. БурденкоРоссияN.N. Burdenko Main Military Clinical HospitalRussian Federation201905082024212191198Copyright © Зубкин М.Л., Ким И.Г., Аришева О.С., Томилина Н.А., Червинко В.И., Столяревич Е.С., Артюхина Л.Ю., Островская И.В., Фролова Н.Ф., Семененко Т.А., Крюков Е.В., 20242024Зубкин М.Л., Ким И.Г., Аришева О.С., Томилина Н.А., Червинко В.И., Столяревич Е.С., Артюхина Л.Ю., Островская И.В., Фролова Н.Ф., Семененко Т.А., Крюков Е.В.Zubkin M.L., Kim I.G., Arisheva O.S., Tomilina N.A., Chervinko V.I., Stolyarevich E.S., Artyuhina L.Y., Ostrovskaya I.V., Frolova N.F., Semenenko T.A., Kryukov E.V.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://journal.nephro.ru/jour/article/view/263

Хроническая HCV-инфекция является серьезной проблемой трансплантации почки, ограничивающей эффективность этой операции. Цель исследования: оценить эффективность и безопасность препаратов прямого противовирусных действия (ПППД) у реципиентов почечного трансплантата (РПТ) с хронической HCV-инфекцией. Материалы и методы. В исследование включено 24 РПТ с хроническим гепатитом С в возрасте 51,5±10,2 лет (75% мужчин). Длительность пост-трансплантационного периода к началу противовирусной терапии (ПВТ) достигала 6,4±5,7 лет. СКФ составляла 58,9±18,9 мл/мин/1,73 м2 (у всех - выше 30 мл/мин/1,73 м2 по СKD-EPI), протеинурия не превышала 0,18 (0,1;0,5) г/сут. Поддерживающая иммуносупрессивная терапия включала преднизолон, микофенолаты и ингибиторы кальциневрина (ИКН: Taк 16/ЦиА 8). Длительность HCV-инфекции от момента ее диагностики до начала ПВТ составила 10,4±7,3 лет. В исследуемой группе преобладал 1b генотип HCV (у 50% больных), вирусная нагрузка достигала 1,3×106 (6,8×104; 8,1×106). У половины больных выявлялся умеренный (F2) или выраженный (F3) фиброз, у 8,3% пациентов был диагностирован цирроз печени (F4 по шкале METAVIR). 5 пациентов получали софосбувир (SOF) 400 мг/сут в комбинации с даклатасвиром (DCV) 60 мг/сут и рибавирином (RBV) 15 мг/кг/сут (12 нед.), 14 больных - SOF+DCV (12 нед.), еще 5 человек - SOF+RBV (24 нед.). Длительность наблюдения после окончания терапии составила 22,8±10,2 мес. Результаты. Через 8,3±3,4 недели после начала ПВТ у всех РПТ была достигнута авиремия, сопровождавшаяся достоверным снижением уровней АЛТ (p<0,0001) и АСТ (p<0,001). Устойчивый вирусологический ответ через 12 и 24 недели после окончания лечения констатирован в 100% случаев. Степень фиброза печени регрессировала с 11,7±5,1 кПа до 7,1±2,7 кПа, p<0,001. На фоне ПВТ у 2/3 больных наблюдалось снижение концентраций ИКН в крови: ЦиА - с 111,3±29,9 до 88,4±25,4 нг/мл (p<0,027) и Так - с 7,5±1,3 до 5,3±1,5 нг/мл (p<0,001), что потребовало повышения доз препаратов. Функция почечного трансплантата и уровень протеинурии оставались стабильными. Серьезные нежелательные явления (НЯ), за исключением эпизода острого отторжения, не наблюдались. Выводы. ПППД эффективны и безопасны у РПТ с ХГС. Высокая вероятность снижения концентраций ИКН в процессе лечения требует тщательного их мониторинга во избежание дисфункции почечного трансплантата.

Chronic HCV infection is a serious problem of kidney transplantation, limiting the effectiveness of this operation. Aim: to evaluate the efficacy and safety of direct-acting antiviral therapy (DAAT) in kidney graft recipients (KGR) with chronic hepatitis C (CHC). Methods: the study included 24 KGR with CHC who underwent DAAT. The mean age was 51.5±10.2 years (men 75%). The duration of post-transplant period at the beginning of therapy was 6.4±5.7 years, duration of HCV infection was 10.4±7.3 years. GFR was 58.9±18.9 ml/min/1.73 m2 (all above 30 ml/min/1.73 m2 by CKD-EPI). 50% of KGR had 1b genotype HCV. Level of HCV RNA reached 1.3×106 (6.8×104; 8.1×106) IU/ml). Half of the patients had F2 or F3 stage of fibrosis, liver cirrhosis (F4 on the METAVIR scale) was diagnosed in 8.3% of recipients. 5 patients received SOF 400 mg/day with DCV 60 mg/day and 15 mg/kg/day of RBV for 12 weeks, 14 patients received SOF+DCV for 12 weeks, and 5 patients for 24 weeks. The duration of follow-up period after the end of the therapy was 22.8±10.2 months. Results: aviremia was achieved in 100% pts after 8.3±3.4 weeks of DAAT. It was accompanied by a decrease in the levels of ALT (p<0.0001) and AST (p<0.001). Sustained virological response was observed in all patients after 12 and 24 weeks after the end of the therapy. The degree of liver fibrosis regressed from 11.7±5.1 kPa to 7.1±2.7 kPa (p<0,001) at 12 weeks after the end of therapy. During of DAAT, 2/3 of patients had a decrease of blood level of CNI: Cs - from 111.3±29.9 to 88.4±25.4 ng/ml (p<0.027), and Tac - from 7.5±1.3 to 5.3±1.5 ng/ml (p<0.001). Renal graft function remained stable, as well as the severity of proteinuria. There were no cases of serious complications of treatment, except for an episode of acute rejection. Conclusion: direct-acting antiviral agents are effective and save in renal transplant recipients with chronic HCV infection. The probability of reducing of the blood levels of CNI during treatment requires careful monitoring to avoid renal graft dysfunction.

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The authors declare that there are no conflicts of interest present.