vtioВестник трансплантологии и искусственных органовRussian Journal of Transplantology and Artificial Organs1995-1191Academician V.I.Shumakov National Medical Research Center of Transplantology and Artificial Organs", Ministry of Health of the Russian Federation10.15825/1995-1191-2016-1-67-77vtio-621Research ArticleОбзор литературыLiterature ReviewsКЛИНИЧЕСКОЕ ЗНАЧЕНИЕ ЦИТОМЕГАЛОВИРУСНОЙ ИНФЕКЦИИ У ДЕТЕЙ ПОСЛЕ ТРАНСПЛАНТАЦИИ ПЕЧЕНИCLINICAL SIGNIFICANCE OF CYTOMEGALOVIRUS INFECTION IN PEDIATRIC LIVER TRANSPLANT RECIPIENTSЦирульниковаО. М.TsiroulnikovaO. M.

Москва

1, Shchukinskaya st., Moscow, 123182

ЖилкинИ. В.ZhilkinI. V.

123182, г. Москва, ул. Щукинская, д. 1

Moscow

izhilkin@gmail.comАхаладзеД. Г.AkhaladzeD. G.

Москва

Moscow

ФГБУ «Федеральный научный центр трансплантологии и искусственных органов имени академика В.И. Шумакова» Минздрава России; Кафедра трансплантологии и искусственных органов ГБОУ ВПО «Первый МГМУ им. И.М. Сеченова»РоссияV.I. Shumakov Federal Research Center of Transplantology and Artificial Organs of the Ministry of Healthcare of the Russian Federation; I.M. Sechenov First Moscow State Medical University, Department of transplantology and artificial organsRussian FederationФГБУ «Федеральный научный центр трансплантологии и искусственных органов имени академика В.И. Шумакова» Минздрава РоссииРоссияV.I. Shumakov Federal Research Center of Transplantology and Artificial Organs of the Ministry of Healthcare of the Russian FederationRussian Federation2016160420161816777Copyright © Цирульникова О.М., Жилкин И.В., Ахаладзе Д.Г., 20162016Цирульникова О.М., Жилкин И.В., Ахаладзе Д.Г.Tsiroulnikova O.M., Zhilkin I.V., Akhaladze D.G.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://journal.transpl.ru/vtio/article/view/621

Трансплантация печени является единственным возможным путем лечения многих форм хронических заболеваний печени терминальной стадии у детей. Цитомегаловирус – наиболее распространенная и значимая инфекция у детей после трансплантации печени с развитием эпизодов ЦМВ-инфекции (ЦМВИ) или ЦМВ-заболевания. ЦМВИ ассоциирована с повышенным риском потери трансплантата. В обзоре литературы представлены такие аспекты, как этиология и эпидемиология ЦМВИ после трансплантации печени детям, применяемые подходы диагностики и профилактики ЦМВИ, алгоритмы дозирования валганцикловира, а также методы профилактики осложнений течения ЦМВИ. Также представлены последние данные о текущих стратегиях профилактики ЦМВИ в мировой практике.

Liver transplantation is a life-saving procedure for many forms of end-stage liver disease in pediatrics. Cytomegalovirus (CMV) is the most common and signifi cant posttransplant infection after pediatric liver transplant (PLT) with developing an episode of CMV infection or disease. It is well known that CMV increases risk of graft loss. The review presents aspects of etiology and epidemiology of CMV after PLT, approaches employed in diagnostics and prophylaxis of CMV, algorithms for valganciclovir dosing and methods to prevent complications associated with CMV. The latest data on current prevention strategies in pediatric liver transplantation centers in the world are also presented.

трансплантация печени детямцитомегаловирусная инфекцияпрофилактика цитомегаловирусной инфекцииpediatric liver transplantationcytomegalovirus infectionantiviral prophylaxispreemptive therapyantiviral therapyReferencesГотье СВ, Константинов БА, Цирульникова ОМ. Трансплантация печени. М.: МИА, 2008. Gautier SV, Konstantinov BA, Tsirulnikova OM. Transplantatsiya pecheni. M.: MIA, 2008.Готье СВ, Константинов БА, Цирульникова ОМ. Трансплантация печени. М.: МИА, 2008. Gautier SV, Konstantinov BA, Tsirulnikova OM. Transplantatsiya pecheni. M.: MIA, 2008.Åsberg A, Rollag H, Hartmann A. Valganciclovir for the prevention and treatment of CMV in solid organ transplant recipients. Expert Opin Pharmacother. April 2010. http://www.tandfonline.com/doi/abs/10.1517/14656561003742954?journalCode=ieop20. Accessed November 24, 2015.Åsberg A, Rollag H, Hartmann A. Valganciclovir for the prevention and treatment of CMV in solid organ transplant recipients. Expert Opin Pharmacother. April 2010. http://www.tandfonline.com/doi/abs/10.1517/14656561003742954?journalCode=ieop20. Accessed November 24, 2015.Beam E, Razonable RR. Cytomegalovirus in solid organ transplantation: epidemiology, prevention, and treatment. Curr Infect Dis Rep. 2012; 14 (6): 633–641. doi:10.1007/s11908-012-0292-2.Beam E, Razonable RR. Cytomegalovirus in solid organ transplantation: epidemiology, prevention, and treatment. Curr Infect Dis Rep. 2012; 14 (6): 633–641. doi:10.1007/s11908-012-0292-2.Fishman J, Emery V, Freeman R et al. Cytomegalovirus in transplantation – Challenging the status quo. Clin Transplant. 2007; 21 (2): 149–158. doi:10.1111/j.1399-0012.2006.00618.x.Fishman J, Emery V, Freeman R et al. Cytomegalovirus in transplantation – Challenging the status quo. Clin Transplant. 2007; 21 (2): 149–158. doi:10.1111/j.1399-0012.2006.00618.x.Shepherd RW, Turmelle Y, Nadler M et al. Risk factors for rejection and infection in pediatric liver transplantation. Am J Transplant. 2008; 8 (2): 396–403. doi:10.1111/j.1600-6143.2007.02068.x.Shepherd RW, Turmelle Y, Nadler M et al. Risk factors for rejection and infection in pediatric liver transplantation. Am J Transplant. 2008; 8 (2): 396–403. doi:10.1111/j.1600-6143.2007.02068.x.Razonable RR, Paya CV. Herpesvirus infections in transplant recipients: current challenges in the clinical management of cytomegalovirus and Epstein–Barr virus infections. Herpes. 2003; 10 (3): 60–65. http://europepmc.org/abstract/med/14759337. Accessed November 25, 2015.Razonable RR, Paya CV. Herpesvirus infections in transplant recipients: current challenges in the clinical management of cytomegalovirus and Epstein–Barr virus infections. Herpes. 2003; 10 (3): 60–65. http://europepmc.org/abstract/med/14759337. Accessed November 25, 2015.Razonable RR, Emery VC. Management of CMV infection and disease in transplant patients. 27–29 February 2004. Herpes. 2004; 11 (3): 77–86. http://www.ncbi.nlm.nih.gov/pubmed/15960905. Accessed November 25, 2015.Razonable RR, Emery VC. Management of CMV infection and disease in transplant patients. 27–29 February 2004. Herpes. 2004; 11 (3): 77–86. http://www.ncbi.nlm.nih.gov/pubmed/15960905. Accessed November 25, 2015.Цирульникова ОМ, Цирульникова ИЕ. Инфекции в трансплантологии; под ред. С.В. Готье. 2009; 223–246. Tsirulnikova OM, Tsirulnikova IE. Infekcii v transplantologii; pod red. Gautier S.V. 2009; 223–246.Цирульникова ОМ, Цирульникова ИЕ. Инфекции в трансплантологии; под ред. С.В. Готье. 2009; 223–246. Tsirulnikova OM, Tsirulnikova IE. Infekcii v transplantologii; pod red. Gautier S.V. 2009; 223–246.Bowman JS, Green M, Scantlebury VP et al. OKT3 and viral disease in pediatric liver transplant recipients. Clin Transplant. 1991; 5 (4): 294–300. http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=3002137&tool=pmcentrez&rendertype=abstract. Accessed November 26, 2015.Bowman JS, Green M, Scantlebury VP et al. OKT3 and viral disease in pediatric liver transplant recipients. Clin Transplant. 1991; 5 (4): 294–300. http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=3002137&tool=pmcentrez&rendertype=abstract. Accessed November 26, 2015.Kawano Y, Mizuta K, Sanada Y et al. Risk Factors of Cytomegalovirus Infection After Pediatric Liver Transplantation. Transplant Proc. 2014; 46 (10): 3543–3547. doi:10.1016/j.transproceed.2014.09.150.Kawano Y, Mizuta K, Sanada Y et al. Risk Factors of Cytomegalovirus Infection After Pediatric Liver Transplantation. Transplant Proc. 2014; 46 (10): 3543–3547. doi:10.1016/j.transproceed.2014.09.150.Indolfi G, Heaton N, Smith M, Mieli-Vergani G, Zuckerman M. Effect of early EBV and/or CMV viremia on graft function and acute cellular rejection in pediatric liver transplantation. Clin Transpl. 2012; 26 (1): E55–E61. doi:10.1111/j.1399-0012.2011.01535.x.Indolfi G, Heaton N, Smith M, Mieli-Vergani G, Zuckerman M. Effect of early EBV and/or CMV viremia on graft function and acute cellular rejection in pediatric liver transplantation. Clin Transpl. 2012; 26 (1): E55–E61. doi:10.1111/j.1399-0012.2011.01535.x.Jain A, Orloff M, Kashyap R et al. Does valganciclovir hydrochloride (valcyte) provide effective prophylaxis against cytomegalovirus infection in liver transplant recipients? Transplant Proc. 2005; 37 (7): 3182–3186. doi:10.1016/j.transproceed.2005.07.032.Jain A, Orloff M, Kashyap R et al. Does valganciclovir hydrochloride (valcyte) provide effective prophylaxis against cytomegalovirus infection in liver transplant recipients? Transplant Proc. 2005; 37 (7): 3182–3186. doi:10.1016/j.transproceed.2005.07.032.Singh N, Wannstedt C, Keyes L, Wagener MM, Gayowski T, Cacciarelli TV. Indirect outcomes associated with cytomegalovirus (opportunistic infections, hepatitis C virus sequelae, and mortality) in liver-transplant recipients with the use of preemptive therapy for 13 years. Transplantation. 2005; 79 (10): 1428–1434. http://www.ncbi.nlm.nih.gov/pubmed/15912115. Accessed November 26, 2015.Singh N, Wannstedt C, Keyes L, Wagener MM, Gayowski T, Cacciarelli TV. Indirect outcomes associated with cytomegalovirus (opportunistic infections, hepatitis C virus sequelae, and mortality) in liver-transplant recipients with the use of preemptive therapy for 13 years. Transplantation. 2005; 79 (10): 1428–1434. http://www.ncbi.nlm.nih.gov/pubmed/15912115. Accessed November 26, 2015.Arthurs SK, Eid AJ, Pedersen RA et al. Delayed-onset primary cytomegalovirus disease after liver transplantation. Liver Transpl. 2007; 13 (12): 1703–1709. doi:10.1002/lt.21280.Arthurs SK, Eid AJ, Pedersen RA et al. Delayed-onset primary cytomegalovirus disease after liver transplantation. Liver Transpl. 2007; 13 (12): 1703–1709. doi:10.1002/lt.21280.Gane E, Saliba F, Valdecasas GJ et al. Randomised trial of effi cacy and safety of oral ganciclovir in the prevention of cytomegalovirus disease in liver-transplant recipients. Lancet. 1997; 350 (9093): 1729–1733. doi:10.1016/S0140-6736(97)05535-9.Gane E, Saliba F, Valdecasas GJ et al. Randomised trial of effi cacy and safety of oral ganciclovir in the prevention of cytomegalovirus disease in liver-transplant recipients. Lancet. 1997; 350 (9093): 1729–1733. doi:10.1016/S0140-6736(97)05535-9.Paya C, Humar A, Dominguez E et al. Efficacy and safety of valganciclovir vs. oral ganciclovir for prevention of cytomegalovirus disease in solid organ transplant recipients. Am J Transplant. 2004; 4 (4): 611–620. doi:10.1111/j.1600-6143.2004.00382.x.Paya C, Humar A, Dominguez E et al. Efficacy and safety of valganciclovir vs. oral ganciclovir for prevention of cytomegalovirus disease in solid organ transplant recipients. Am J Transplant. 2004; 4 (4): 611–620. doi:10.1111/j.1600-6143.2004.00382.x.Fishman JA, Emery V, Freeman R et al. Cytomegalovirus in transplantation – challenging the status quo. Clin Transplant. 21 (2): 149–158. doi:10.1111/j.1399-0012.2006.00618.x.Fishman JA, Emery V, Freeman R et al. Cytomegalovirus in transplantation – challenging the status quo. Clin Transplant. 21 (2): 149–158. doi:10.1111/j.1399-0012.2006.00618.x.Fishman JA, Rubin RH. Infection in organ-transplant recipients. N Engl J Med. 1998; 338 (24): 1741–1751. doi:10.1056/NEJM199806113382407.Fishman JA, Rubin RH. Infection in organ-transplant recipients. N Engl J Med. 1998; 338 (24): 1741–1751. doi:10.1056/NEJM199806113382407.Ljungman P, Griffi ths P, Paya C. Defi nitions of cytomegalovirus infection and disease in transplant recipients. Clin Infect Dis. 2002; 34 (8): 1094–1097. doi:10.1086/339329.Ljungman P, Griffi ths P, Paya C. Defi nitions of cytomegalovirus infection and disease in transplant recipients. Clin Infect Dis. 2002; 34 (8): 1094–1097. doi:10.1086/339329.Kelly DA, Bucuvalas JC, Alonso EM et al. Long-term medical management of the pediatric patient after liver transplantation: 2013 practice guideline by the American Association for the Study of Liver Diseases and the American Society of Transplantation. Liver Transpl. 2013; 19 (8): 798–825. doi:10.1002/lt.23697.Kelly DA, Bucuvalas JC, Alonso EM et al. Long-term medical management of the pediatric patient after liver transplantation: 2013 practice guideline by the American Association for the Study of Liver Diseases and the American Society of Transplantation. Liver Transpl. 2013; 19 (8): 798–825. doi:10.1002/lt.23697.Fica A, Cervera C, Pérez N et al. Immunohistochemically proven cytomegalovirus end-organ disease in solid organ transplant patients: clinical features and usefulness of conventional diagnostic tests. Transpl Infect Dis. 2007; 9 (3): 203–210. doi:10.1111/j.1399-3062.2007.00220.x.Fica A, Cervera C, Pérez N et al. Immunohistochemically proven cytomegalovirus end-organ disease in solid organ transplant patients: clinical features and usefulness of conventional diagnostic tests. Transpl Infect Dis. 2007; 9 (3): 203–210. doi:10.1111/j.1399-3062.2007.00220.x.Squires JE, Sisk RA, Balistreri WF, Kohli R. Isolated unilateral cytomegalovirus retinitis: a rare long-term complication after pediatric liver transplantation. Pediatr Transplant. 2013; 17 (1): E16–E19. doi:10.1111/j.1399-3046.2012.01752.x.Squires JE, Sisk RA, Balistreri WF, Kohli R. Isolated unilateral cytomegalovirus retinitis: a rare long-term complication after pediatric liver transplantation. Pediatr Transplant. 2013; 17 (1): E16–E19. doi:10.1111/j.1399-3046.2012.01752.x.Gotthardt DN, Senft J, Sauer P et al. Occult cytomegalovirus cholangitis as a potential cause of cholestatic complications after orthotopic liver transplantation? A study of cytomegalovirus DNA in bile. Liver Transpl. 2013; 19 (10): 1142–1150. doi:10.1002/lt.23713.Gotthardt DN, Senft J, Sauer P et al. Occult cytomegalovirus cholangitis as a potential cause of cholestatic complications after orthotopic liver transplantation? A study of cytomegalovirus DNA in bile. Liver Transpl. 2013; 19 (10): 1142–1150. doi:10.1002/lt.23713.Hoppe L, Marroni CA, Bressane R et al. Impact of cytomegalovirus infection on long-term survival after orthotopic liver transplantation. Transplant Proc. 2006; 38 (6): 1924–1925. doi:10.1016/j.transproceed.2006.06.074.Hoppe L, Marroni CA, Bressane R et al. Impact of cytomegalovirus infection on long-term survival after orthotopic liver transplantation. Transplant Proc. 2006; 38 (6): 1924–1925. doi:10.1016/j.transproceed.2006.06.074.Sun H-Y, Wagener MM, Singh N. Prevention of posttransplant cytomegalovirus disease and related outcomes with valganciclovir: a systematic review. Am J Transplant. 2008; 8 (10): 2111–2118. doi:10.1111/j.1600-6143.2008.02369.x.Sun H-Y, Wagener MM, Singh N. Prevention of posttransplant cytomegalovirus disease and related outcomes with valganciclovir: a systematic review. Am J Transplant. 2008; 8 (10): 2111–2118. doi:10.1111/j.1600-6143.2008.02369.x.Kullberg-Lindh C, Ascher H, Krantz M, Lindh M. Quantitative analysis of CMV DNA in children the fi rst year after liver transplantation. Pediatr Transplant. 2003; 7 (4): 296–301. doi:10.1034/j.1399-3046.2003.00086.x.Kullberg-Lindh C, Ascher H, Krantz M, Lindh M. Quantitative analysis of CMV DNA in children the fi rst year after liver transplantation. Pediatr Transplant. 2003; 7 (4): 296–301. doi:10.1034/j.1399-3046.2003.00086.x.Kanj SS, Sharara AI, Clavien P-A, Hamilton JD. Cytomegalovirus Infection Following Liver Transplantation: Review of the Literature. Clin Infect Dis. 1996; 22 (3): 537–549. doi:10.1093/clinids/22.3.537.Kanj SS, Sharara AI, Clavien P-A, Hamilton JD. Cytomegalovirus Infection Following Liver Transplantation: Review of the Literature. Clin Infect Dis. 1996; 22 (3): 537–549. doi:10.1093/clinids/22.3.537.Madan RP, Campbell AL, Shust GF et al. A hybrid strategy for the prevention of cytomegalovirus-related complications in pediatric liver transplantation recipients. Transplantation. 2009; 87 (9): 1318–1324. doi:10.1097/TP.0b013e3181a19cda.Madan RP, Campbell AL, Shust GF et al. A hybrid strategy for the prevention of cytomegalovirus-related complications in pediatric liver transplantation recipients. Transplantation. 2009; 87 (9): 1318–1324. doi:10.1097/TP.0b013e3181a19cda.John LR. Forsythe. Transplantation. Elsevier Science; 2013.John LR. Forsythe. Transplantation. Elsevier Science; 2013.Falagas ME, Arbo M, Ruthazer R et al. Cytomegalovirus disease is associated with increased cost and hospital length of stay among orthotopic liver transplant recipients. Transplantation. 1997; 63 (11): 1595–1601. http://www.ncbi.nlm.nih.gov/pubmed/9197352. Accessed November 25, 2015.Falagas ME, Arbo M, Ruthazer R et al. Cytomegalovirus disease is associated with increased cost and hospital length of stay among orthotopic liver transplant recipients. Transplantation. 1997; 63 (11): 1595–1601. http://www.ncbi.nlm.nih.gov/pubmed/9197352. Accessed November 25, 2015.Hardinger KL, Schnitzler MA, Brennan DC. Cytomegalovirus increases the rate of graft loss after liver transplantation. Am J Transpl. 2003; 5: 523.Hardinger KL, Schnitzler MA, Brennan DC. Cytomegalovirus increases the rate of graft loss after liver transplantation. Am J Transpl. 2003; 5: 523.Gupta P, Hart J, Cronin D, Kelly S, Millis JM, Brady L. Risk factors for chronic rejection after pediatric liver transplantation. Transplantation. 2001; 72 (6): 1098–1102. http://www.ncbi.nlm.nih.gov/pubmed/11579307. Accessed November 26, 2015.Gupta P, Hart J, Cronin D, Kelly S, Millis JM, Brady L. Risk factors for chronic rejection after pediatric liver transplantation. Transplantation. 2001; 72 (6): 1098–1102. http://www.ncbi.nlm.nih.gov/pubmed/11579307. Accessed November 26, 2015.Evans PC, Soin A, Wreghitt TG, Taylor CJ, Wight DG, Alexander GJ. An association between cytomegalovirus infection and chronic rejection after liver transplantation. Transplantation. 2000; 69 (1): 30–35. http://www.ncbi.nlm.nih.gov/pubmed/10653376. Accessed November 26, 2015.Evans PC, Soin A, Wreghitt TG, Taylor CJ, Wight DG, Alexander GJ. An association between cytomegalovirus infection and chronic rejection after liver transplantation. Transplantation. 2000; 69 (1): 30–35. http://www.ncbi.nlm.nih.gov/pubmed/10653376. Accessed November 26, 2015.Rubin RH. Importance of CMV in the transplant population. Transpl Infect Dis. 1999; 1 (Suppl. 1): 3–7. http://europepmc.org/abstract/med/11565584. Accessed November 26, 2015.Rubin RH. Importance of CMV in the transplant population. Transpl Infect Dis. 1999; 1 (Suppl. 1): 3–7. http://europepmc.org/abstract/med/11565584. Accessed November 26, 2015.Paya CV. Indirect effects of CMV in the solid organ transplant patient. Transpl Infect Dis. 1999; 1 (Suppl. 1): 8–12. http://europepmc.org/abstract/med/11565588. Accessed November 26, 2015.Paya CV. Indirect effects of CMV in the solid organ transplant patient. Transpl Infect Dis. 1999; 1 (Suppl. 1): 8–12. http://europepmc.org/abstract/med/11565588. Accessed November 26, 2015.Milan A, Sampaio AM, Guardia AC et al. Identifi cation of Bacterial Infections and Clinical Manifestation Associated With Cytomegalovirus in Liver Transplantation Patients. Transplant Proc. 2013; 45 (3): 1130–1132. doi:10.1016/j.transproceed.2013.02.016.Milan A, Sampaio AM, Guardia AC et al. Identifi cation of Bacterial Infections and Clinical Manifestation Associated With Cytomegalovirus in Liver Transplantation Patients. Transplant Proc. 2013; 45 (3): 1130–1132. doi:10.1016/j.transproceed.2013.02.016.Harkins L, Volk AL, Samanta M et al. Specifi c localisation of human cytomegalovirus nucleic acids and proteins in human colorectal cancer. Lancet (London, England). 2002; 360 (9345): 1557–1563. doi:10.1016/S0140- 6736(02)11524-8.Harkins L, Volk AL, Samanta M et al. Specifi c localisation of human cytomegalovirus nucleic acids and proteins in human colorectal cancer. Lancet (London, England). 2002; 360 (9345): 1557–1563. doi:10.1016/S0140- 6736(02)11524-8.Samanta M, Harkins L, Klemm K, Britt WJ, Cobbs CS. High prevalence of human cytomegalovirus in prostatic intraepithelial neoplasia and prostatic carcinoma. J Urol. 2003; 170 (3): 998–1002. doi:10.1097/01.ju.0000080263.46164.97.Samanta M, Harkins L, Klemm K, Britt WJ, Cobbs CS. High prevalence of human cytomegalovirus in prostatic intraepithelial neoplasia and prostatic carcinoma. J Urol. 2003; 170 (3): 998–1002. doi:10.1097/01.ju.0000080263.46164.97.Basgoz N, Preiksaitis JK. Post-transplant lymphoproliferative disorder. Infect Dis Clin North Am. 1995; 9 (4): 901–923. http://europepmc.org/abstract/med/8747772. Accessed November 26, 2015.Basgoz N, Preiksaitis JK. Post-transplant lymphoproliferative disorder. Infect Dis Clin North Am. 1995; 9 (4): 901–923. http://europepmc.org/abstract/med/8747772. Accessed November 26, 2015.Mañez R, Breinig MC, Linden P et al. Posttransplant Lymphoproliferative Disease in Primary Epstein–Barr Virus Infection after Liver Transplantation: The Role of Cytomegalovirus Disease. J Infect Dis. 1997; 176 (6): 1462–1467. doi:10.1086/514142.Mañez R, Breinig MC, Linden P et al. Posttransplant Lymphoproliferative Disease in Primary Epstein–Barr Virus Infection after Liver Transplantation: The Role of Cytomegalovirus Disease. J Infect Dis. 1997; 176 (6): 1462–1467. doi:10.1086/514142.Cobbs CS, Harkins L, Samanta M et al. Human Cytomegalovirus Infection and Expression in Human Malignant Glioma. Cancer Res. 2002; 62 (12): 3347–3350. http://cancerres.aacrjournals.org/content/62/12/3347.short.Accessed November 26, 2015.Cobbs CS, Harkins L, Samanta M et al. Human Cytomegalovirus Infection and Expression in Human Malignant Glioma. Cancer Res. 2002; 62 (12): 3347–3350. http://cancerres.aacrjournals.org/content/62/12/3347.short.Accessed November 26, 2015.Smith BA, Shuchman M. Problem of nonadherence in chronically ill adolescents: strategies for assessment and intervention. Curr Opin Pediatr. 2005; 17 (5): 613–618. doi:10.1097/01.mop.0000176443.26872.6e.Smith BA, Shuchman M. Problem of nonadherence in chronically ill adolescents: strategies for assessment and intervention. Curr Opin Pediatr. 2005; 17 (5): 613–618. doi:10.1097/01.mop.0000176443.26872.6e.Danziger-Isakov L, Bucavalas J. Current prevention strategies against cytomegalovirus in the studies in pediatric liver transplantation (SPLIT) centers. Am J Transplant. 2014; 14 (8): 1908–1911. doi:10.1111/ajt.12755.Danziger-Isakov L, Bucavalas J. Current prevention strategies against cytomegalovirus in the studies in pediatric liver transplantation (SPLIT) centers. Am J Transplant. 2014; 14 (8): 1908–1911. doi:10.1111/ajt.12755.Bedel AN, Hemmelgarn TS, Kohli R. Retrospective review of the incidence of cytomegalovirus infection and diseaes post liver transplantation in pediatric patients: comparison of prophylactic oral ganciclovir versus oral valganciclovir. Liver Transpl. 2012; 18 (3): 347–354. doi:10.1002/lt.22471.Retrospective.Bedel AN, Hemmelgarn TS, Kohli R. Retrospective review of the incidence of cytomegalovirus infection and diseaes post liver transplantation in pediatric patients: comparison of prophylactic oral ganciclovir versus oral valganciclovir. Liver Transpl. 2012; 18 (3): 347–354. doi:10.1002/lt.22471.Retrospective.Müller V, Perrakis A, Meyer J et al. The value of preemptive therapy for cytomegalovirus after liver transplantation. Transplant Proc. 2012; 44 (5): 1357–1361. doi:10.1016/j.transproceed.2011.11.067.Müller V, Perrakis A, Meyer J et al. The value of preemptive therapy for cytomegalovirus after liver transplantation. Transplant Proc. 2012; 44 (5): 1357–1361. doi:10.1016/j.transproceed.2011.11.067.Lee S, Razonable R. Current concepts on cytomegalovirus infection after liver transplantation. World j hepatol. 2010; 2 (9): 325–336. doi:10.4254/wjh.v2.i9.325.Lee S, Razonable R. Current concepts on cytomegalovirus infection after liver transplantation. World j hepatol. 2010; 2 (9): 325–336. doi:10.4254/wjh.v2.i9.325.Krampe K, Briem-Richter A, Fischer L, Nashan B, Ganschow R. The value of immunoprophylaxis for cytomegalovirus infection with intravenous immunoglobulin in pediatric liver transplant recipients receiving a low-dose immunosupressive regimen. Pediatr Transplant. 2010; 14 (3): 67–71. doi:10.1111/j.1399-3046.2008.01120.x.Krampe K, Briem-Richter A, Fischer L, Nashan B, Ganschow R. The value of immunoprophylaxis for cytomegalovirus infection with intravenous immunoglobulin in pediatric liver transplant recipients receiving a low-dose immunosupressive regimen. Pediatr Transplant. 2010; 14 (3): 67–71. doi:10.1111/j.1399-3046.2008.01120.x.Hodson EM, Jones CA, Webster AC et al. Antiviral medications to prevent cytomegalovirus disease and early death in recipients of solid-organ transplants: a systematic review of randomised controlled trials. Lancet (London, England). 2005; 365 (9477): 2105–2115. doi:10.1016/S0140-6736(05)66553-1.Hodson EM, Jones CA, Webster AC et al. Antiviral medications to prevent cytomegalovirus disease and early death in recipients of solid-organ transplants: a systematic review of randomised controlled trials. Lancet (London, England). 2005; 365 (9477): 2105–2115. doi:10.1016/S0140-6736(05)66553-1.Sester U, Gärtner BC, Wilkens H et al. Differences in CMV-specifi c T-cell levels and long-term susceptibility to CMV infection after kidney, heart and lung transplantation. Am J Transplant. 2005; 5 (6): 1483–1489. doi:10.1111/j.1600-6143.2005.00871.x.Sester U, Gärtner BC, Wilkens H et al. Differences in CMV-specifi c T-cell levels and long-term susceptibility to CMV infection after kidney, heart and lung transplantation. Am J Transplant. 2005; 5 (6): 1483–1489. doi:10.1111/j.1600-6143.2005.00871.x.Cope AV, Sabin C, Burroughs A, Rolles K, Griffi ths PD, Emery VC. Interrelationships among Quantity of Human Cytomegalovirus (HCMV) DNA in Blood, Donor–Recipient Serostatus, and Administration of Methylprednisolone as Risk Factors for HCMV Disease following Liver Transplantation. J Infect Dis. 1997; 176 (6): 1484–1490. doi:10.1086/514145.Cope AV, Sabin C, Burroughs A, Rolles K, Griffi ths PD, Emery VC. Interrelationships among Quantity of Human Cytomegalovirus (HCMV) DNA in Blood, Donor–Recipient Serostatus, and Administration of Methylprednisolone as Risk Factors for HCMV Disease following Liver Transplantation. J Infect Dis. 1997; 176 (6): 1484–1490. doi:10.1086/514145.Razonable A. Cytomegalovirus disease in solid organ transplant recipients: advances lead to new challenges and opportunities. Curr Opin Organ Transplant. 2008; 2 (1): 610–617. http://www.turkiyeklinikleri.com/article/en-cytomegalovirus-disease-in-solid-organ-transplantrecipients-advances-lead-to-new-challenges-and-opportunities-56994.html. Accessed November 26, 2015.Razonable A. Cytomegalovirus disease in solid organ transplant recipients: advances lead to new challenges and opportunities. Curr Opin Organ Transplant. 2008; 2 (1): 610–617. http://www.turkiyeklinikleri.com/article/en-cytomegalovirus-disease-in-solid-organ-transplantrecipients-advances-lead-to-new-challenges-and-opportunities-56994.html. Accessed November 26, 2015.Falagas ME. Effect of Cytomegalovirus Infection Status on First-Year Mortality Rates among Orthotopic Liver Transplant Recipients. Ann Intern Med. 1997; 126 (4): 275. doi:10.7326/0003-4819-126-4-199702150-00003.Falagas ME. Effect of Cytomegalovirus Infection Status on First-Year Mortality Rates among Orthotopic Liver Transplant Recipients. Ann Intern Med. 1997; 126 (4): 275. doi:10.7326/0003-4819-126-4-199702150-00003.Falagas ME, Paya C, Ruthazer R et al. Signifi cance of Cytomegalovirus for Long-Term Survival after Orthotopic Liver Transplantation. Transplantation. 1998; 66 (8): 1020–1028. doi:10.1097/00007890-199810270-00010.Falagas ME, Paya C, Ruthazer R et al. Signifi cance of Cytomegalovirus for Long-Term Survival after Orthotopic Liver Transplantation. Transplantation. 1998; 66 (8): 1020–1028. doi:10.1097/00007890-199810270-00010.Seehofer D, Rayes N, Neumann UP et al. Changing impact of cytomegalovirus in liver transplantation – a single centre experience of more than 1000 transplantations without ganciclovir prophylaxis. Transpl Int. 2005; 18 (8): 941–948. doi:10.1111/j.1432-2277.2005.00162.x.Seehofer D, Rayes N, Neumann UP et al. Changing impact of cytomegalovirus in liver transplantation – a single centre experience of more than 1000 transplantations without ganciclovir prophylaxis. Transpl Int. 2005; 18 (8): 941–948. doi:10.1111/j.1432-2277.2005.00162.x.de Otero J, Gavalda J, Murio E et al. Cytomegalovirus Disease as a Risk Factor for Graft Loss and Death After Orthotopic Liver Transplantation. Clin Infect Dis. 1998; 26 (4): 865–870. doi:10.1086/513949.de Otero J, Gavalda J, Murio E et al. Cytomegalovirus Disease as a Risk Factor for Graft Loss and Death After Orthotopic Liver Transplantation. Clin Infect Dis. 1998; 26 (4): 865–870. doi:10.1086/513949.Kalil AC, Levitsky J, Lyden E, Stoner J, Freifeld AG. Meta-analysis: the effi cacy of strategies to prevent organ disease by cytomegalovirus in solid organ transplant recipients. Ann Intern Med. 2005; 143 (12): 870–880. http://www.ncbi.nlm.nih.gov/pubmed/16365468. Accessed November 24, 2015.Kalil AC, Levitsky J, Lyden E, Stoner J, Freifeld AG. Meta-analysis: the effi cacy of strategies to prevent organ disease by cytomegalovirus in solid organ transplant recipients. Ann Intern Med. 2005; 143 (12): 870–880. http://www.ncbi.nlm.nih.gov/pubmed/16365468. Accessed November 24, 2015.Razonable RR. Cytomegalovirus infection after liver transplantation: current concepts and challenges. World J Gastroenterol. 2008; 14 (31): 4849–4860. http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2739936&tool=pmcentrez&rendertype=abstract. Accessed November 24, 2015.Razonable RR. Cytomegalovirus infection after liver transplantation: current concepts and challenges. World J Gastroenterol. 2008; 14 (31): 4849–4860. http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2739936&tool=pmcentrez&rendertype=abstract. Accessed November 24, 2015.Paya CV, Wilson JA, Espy MJ et al. Preemptive Use of Oral Ganciclovir to Prevent Cytomegalovirus Infection in Liver Transplant Patients: A Randomized, PlaceboControlled Trial. J Infect Dis. 2002; 185 (7): 854–860. doi:10.1086/339449.Paya CV, Wilson JA, Espy MJ et al. Preemptive Use of Oral Ganciclovir to Prevent Cytomegalovirus Infection in Liver Transplant Patients: A Randomized, PlaceboControlled Trial. J Infect Dis. 2002; 185 (7): 854–860. doi:10.1086/339449.Slifkin M, Ruthazer R, Freeman R et al. Impact of cytomegalovirus prophylaxis on rejection following orthotopic liver transplantation. Liver Transpl. 2005; 11 (12): 1597–1602. doi:10.1002/lt.20523.Slifkin M, Ruthazer R, Freeman R et al. Impact of cytomegalovirus prophylaxis on rejection following orthotopic liver transplantation. Liver Transpl. 2005; 11 (12): 1597–1602. doi:10.1002/lt.20523.Falagas ME, Snydman DR, Ruthazer R et al. Cytomegalovirus immune globulin (CMVIG) prophylaxis is associated with increased survival after orthotopic liver transplantation. The Boston Center for Liver Transplantation CMVIG Study Group. Clin Transplant. 1997; 11 (5 Pt 1): 432–437. http://europepmc.org/abstract/med/9361936. Accessed November 26, 2015.Falagas ME, Snydman DR, Ruthazer R et al. Cytomegalovirus immune globulin (CMVIG) prophylaxis is associated with increased survival after orthotopic liver transplantation. The Boston Center for Liver Transplantation CMVIG Study Group. Clin Transplant. 1997; 11 (5 Pt 1): 432–437. http://europepmc.org/abstract/med/9361936. Accessed November 26, 2015.Campbell AL, Herold BC. Strategies for the prevention of cytomegalovirus infection and disease in pediatric liver transplantation recipients. Pediatr Transplant. 2004; 8 (6): 619–627. doi:10.1111/j.1399-3046.2004.00242.x.Campbell AL, Herold BC. Strategies for the prevention of cytomegalovirus infection and disease in pediatric liver transplantation recipients. Pediatr Transplant. 2004; 8 (6): 619–627. doi:10.1111/j.1399-3046.2004.00242.x.Mumtaz K, Faisal N, Husain S, Morillo A, Renner EL, Shah PS. Universal prophylaxis or preemptive strategy for cytomegalovirus disease after liver transplantation: a systematic review and meta-analysis. Am J Transplant. 2015; 15 (2): 472–481. doi:10.1111/ajt.13044.Mumtaz K, Faisal N, Husain S, Morillo A, Renner EL, Shah PS. Universal prophylaxis or preemptive strategy for cytomegalovirus disease after liver transplantation: a systematic review and meta-analysis. Am J Transplant. 2015; 15 (2): 472–481. doi:10.1111/ajt.13044.Park JM, Lake KD, Arenas JD, Fontana RJ. Efficacy and safety of low-dose valganciclovir in the prevention of cytomegalovirus disease in adult liver transplant recipients. Liver Transpl. 2006; 12 (1): 112–116. doi:10.1002/lt.20562.Park JM, Lake KD, Arenas JD, Fontana RJ. Efficacy and safety of low-dose valganciclovir in the prevention of cytomegalovirus disease in adult liver transplant recipients. Liver Transpl. 2006; 12 (1): 112–116. doi:10.1002/lt.20562.Strippoli GFM, Hodson EM, Jones C, Craig JC. Preemptive treatment for cytomegalovirus viremia to prevent cytomegalovirus disease in solid organ transplant recipients. Transplantation. 2006; 81 (2): 139–145. doi:10.1097/01.tp.0000183970.71366.da.Strippoli GFM, Hodson EM, Jones C, Craig JC. Preemptive treatment for cytomegalovirus viremia to prevent cytomegalovirus disease in solid organ transplant recipients. Transplantation. 2006; 81 (2): 139–145. doi:10.1097/01.tp.0000183970.71366.da.Kotton CN, Kumar D, Caliendo AM et al. Updated international consensus guidelines on the management of cytomegalovirus in solid-organ transplantation. Transplantation. 2013; 96 (4): 333–360. doi:10.1097/TP.0b013e31829df29d.Kotton CN, Kumar D, Caliendo AM et al. Updated international consensus guidelines on the management of cytomegalovirus in solid-organ transplantation. Transplantation. 2013; 96 (4): 333–360. doi:10.1097/TP.0b013e31829df29d.Wloch MK, Smith LR, Boutsaboualoy S et al. Safety and immunogenicity of a bivalent cytomegalovirus DNA vaccine in healthy adult subjects. J Infect Dis. 2008; 197 (12): 1634–1642. doi:10.1086/588385.Wloch MK, Smith LR, Boutsaboualoy S et al. Safety and immunogenicity of a bivalent cytomegalovirus DNA vaccine in healthy adult subjects. J Infect Dis. 2008; 197 (12): 1634–1642. doi:10.1086/588385.Modlin JF, Arvin AM, Fast P, Myers M, Plotkin S, Rabinovich R. Vaccine Development to Prevent Cytomegalovirus Disease: Report from the National Vaccine Advisory Committee. Clin Infect Dis. 2004; 39 (2): 233–239. doi:10.1086/421999.Modlin JF, Arvin AM, Fast P, Myers M, Plotkin S, Rabinovich R. Vaccine Development to Prevent Cytomegalovirus Disease: Report from the National Vaccine Advisory Committee. Clin Infect Dis. 2004; 39 (2): 233–239. doi:10.1086/421999.Togashi J, Sugawara Y, Hashimoto M et al. Oral valganciclovir versus intravenous ganciclovir as preemptive treatment for cytomegalovirus infection after living donor liver transplantation: A randomized trial. Biosci Trends. 2011; 5 (5): 217–222. doi:10.5582/bst.2011.v5.5.217.Togashi J, Sugawara Y, Hashimoto M et al. Oral valganciclovir versus intravenous ganciclovir as preemptive treatment for cytomegalovirus infection after living donor liver transplantation: A randomized trial. Biosci Trends. 2011; 5 (5): 217–222. doi:10.5582/bst.2011.v5.5.217.Åsberg A, Bjerre A, Neely M. New algorithm for valganciclovir dosing in pediatric solid organ transplant recipients. Pediatr Transplant. 2014; 18 (1): 103–111. doi:10.1111/petr.12179.Åsberg A, Bjerre A, Neely M. New algorithm for valganciclovir dosing in pediatric solid organ transplant recipients. Pediatr Transplant. 2014; 18 (1): 103–111. doi:10.1111/petr.12179.Pescovitz MD, Ettenger RB, Strife CF et al. Pharmacokinetics of oral valganciclovir solution and intravenous ganciclovir in pediatric renal and liver transplant recipients. Transpl Infect Dis. 2010; 12 (3): 195–203. doi:10.1111/j.1399-3062.2009.00478.x.Pescovitz MD, Ettenger RB, Strife CF et al. Pharmacokinetics of oral valganciclovir solution and intravenous ganciclovir in pediatric renal and liver transplant recipients. Transpl Infect Dis. 2010; 12 (3): 195–203. doi:10.1111/j.1399-3062.2009.00478.x.Schwartz GJ, Feld LG, Langford DJ. A simple estimate of glomerular fi ltration ratein full-term infants during the fi rst year of life. J Pediatr. 1984; 104 (6): 849–854. doi:10.1016/S0022-3476(84)80479-5.Schwartz GJ, Feld LG, Langford DJ. A simple estimate of glomerular fi ltration ratein full-term infants during the fi rst year of life. J Pediatr. 1984; 104 (6): 849–854. doi:10.1016/S0022-3476(84)80479-5.Villeneuve D, Brothers A, Harvey E et al. Valganciclovir dosing using area under the curve calculations in pediatric solid organ transplant recipients. Pediatr Transplant. 2013; 17 (1): 80–85. doi:10.1111/petr.12030.Villeneuve D, Brothers A, Harvey E et al. Valganciclovir dosing using area under the curve calculations in pediatric solid organ transplant recipients. Pediatr Transplant. 2013; 17 (1): 80–85. doi:10.1111/petr.12030.

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