Basiliximab treatment for steroid-resistant rejection in pediatric patients following liver transplantation for acute liver failure
Corresponding Author
Takanobu Shigeta
Organ Transplantation Center, National Center for Child Health and Development, Tokyo, Japan
Takanobu Shigeta, MD, Department of Transplant Surgery, National Center for Child Health and Development, 2-10-1 Okura, Setagaya, Tokyo 157-8535, Japan
Tel.: +81 3 3416 0181
Fax: +81 3 3416 2222
E-mail: [email protected]
Search for more papers by this authorSeisuke Sakamoto
Organ Transplantation Center, National Center for Child Health and Development, Tokyo, Japan
Search for more papers by this authorHajime Uchida
Organ Transplantation Center, National Center for Child Health and Development, Tokyo, Japan
Search for more papers by this authorKengo Sasaki
Organ Transplantation Center, National Center for Child Health and Development, Tokyo, Japan
Search for more papers by this authorIkumi Hamano
Organ Transplantation Center, National Center for Child Health and Development, Tokyo, Japan
Search for more papers by this authorHiroyuki Kanazawa
Organ Transplantation Center, National Center for Child Health and Development, Tokyo, Japan
Search for more papers by this authorAkinari Fukuda
Organ Transplantation Center, National Center for Child Health and Development, Tokyo, Japan
Search for more papers by this authorToshinao Kawai
Department of Human Genetics, National Center for Child Health and Development, Tokyo, Japan
Search for more papers by this authorMasafumi Onodera
Department of Human Genetics, National Center for Child Health and Development, Tokyo, Japan
Search for more papers by this authorAtsuko Nakazawa
Department of Clinical Pathology, National Center for Child Health and Development, Tokyo, Japan
Search for more papers by this authorMureo Kasahara
Organ Transplantation Center, National Center for Child Health and Development, Tokyo, Japan
Search for more papers by this authorCorresponding Author
Takanobu Shigeta
Organ Transplantation Center, National Center for Child Health and Development, Tokyo, Japan
Takanobu Shigeta, MD, Department of Transplant Surgery, National Center for Child Health and Development, 2-10-1 Okura, Setagaya, Tokyo 157-8535, Japan
Tel.: +81 3 3416 0181
Fax: +81 3 3416 2222
E-mail: [email protected]
Search for more papers by this authorSeisuke Sakamoto
Organ Transplantation Center, National Center for Child Health and Development, Tokyo, Japan
Search for more papers by this authorHajime Uchida
Organ Transplantation Center, National Center for Child Health and Development, Tokyo, Japan
Search for more papers by this authorKengo Sasaki
Organ Transplantation Center, National Center for Child Health and Development, Tokyo, Japan
Search for more papers by this authorIkumi Hamano
Organ Transplantation Center, National Center for Child Health and Development, Tokyo, Japan
Search for more papers by this authorHiroyuki Kanazawa
Organ Transplantation Center, National Center for Child Health and Development, Tokyo, Japan
Search for more papers by this authorAkinari Fukuda
Organ Transplantation Center, National Center for Child Health and Development, Tokyo, Japan
Search for more papers by this authorToshinao Kawai
Department of Human Genetics, National Center for Child Health and Development, Tokyo, Japan
Search for more papers by this authorMasafumi Onodera
Department of Human Genetics, National Center for Child Health and Development, Tokyo, Japan
Search for more papers by this authorAtsuko Nakazawa
Department of Clinical Pathology, National Center for Child Health and Development, Tokyo, Japan
Search for more papers by this authorMureo Kasahara
Organ Transplantation Center, National Center for Child Health and Development, Tokyo, Japan
Search for more papers by this authorAbstract
An IL-2 receptor antagonist, basiliximab, decreases the frequency of ACR in liver transplant (LT) recipients as induction therapy. The aim of this study was to evaluate the effectiveness of basiliximab against SRR as rescue therapy in pediatric LT patients with ALF. Forty pediatric ALF patients underwent LT between November 2005 and July 2013. Among them, seven patients suffering from SRR were enrolled in this study. The median age at LT was 10 months (6–12 months). SRR was defined as the occurrence of refractory rejection after more than two courses of steroid pulse therapy. Basiliximab was administered to all patients. The withdrawal of steroids without deterioration of the liver function was achieved in six patients treated with basiliximab therapy without patient mortality, although one patient developed graft loss and required retransplantation for veno-occlusive disease. The pathological examinations of liver biopsies in the patients suffering from SRR revealed severe centrilobular injuries, particularly fibrosis within one month after LT. We demonstrated the effectiveness and safety of rescue therapy consisting of basiliximab for SRR in pediatric LT recipients with ALF.
References
- 1Chinnakotla S, Klintmalm GB. Induction and maintenance of immunosupression. In: RW Busuttil, GB Klintmalm, eds. Transplantation of the Liver: Immunosupression. Philadelphia: Saunders, 2005: pp. 1213–1234.
10.1016/B978-0-7216-0118-2.50080-X Google Scholar
- 2Hind JM, Kelly DA. Pediatric liver transplantation: Review of the literature 2006–2007. Pediatr Transplant 2009: 13: 14–24.
- 3Martin SR, Atkison P, Anand R, Lindblad AS; SPLIT Research Group. Studies of Pediatric Liver Transplantation 2002: Patient and graft survival and rejection in pediatric recipients of a first liver transplant in the United States and Canada. Pediatr Transplant 2004: 8: 273–283.
- 4D'Alessandro AM, Knechtle SJ, Chin LT, et al. Liver transplantation in pediatric patients: Twenty years of experience at the University of Wisconsin. Pediatr Transplant 2007: 11: 661–670.
- 5Thangarajah D, O'Meara M, Dhawan A. Management of acute rejection in paediatric liver transplantation. Paediatr Drugs 2013: 15: 459–471.
- 6Wallot MA, Mathot M, Janssen M, et al. Long-term survival and late graft loss in pediatric liver transplant recipients – a 15-year single-center experience. Liver Transpl 2002: 8: 615–622.
- 7Schmitt TM, Phillips M, Sawyer RG, et al. Anti-thymocyte globulin for the treatment of acute cellular rejection following liver transplantation. Dig Dis Sci 2010: 55: 3224–3234.
- 8Sindhi R, Webber S, Venkataramanan R, et al. Sirolimus for rescue and primary immunosuppression in transplanted children receiving tacrolimus. Transplantation 2001: 72: 851–855.
- 9Chardot C, Nicoluzzi JE, Janssen M, et al. Use of mycophenolate mofetil as rescue therapy after pediatric liver transplantation. Transplantation 2001: 71: 224–229.
- 10Kerkar N, Morotti RA, Iyer K, et al. Anti-lymphocyte therapy successfully controls late “cholestatic” rejection in pediatric liver transplant recipients. Clin Transplant 2011: 25: E584–E591.
- 11Berard JL, Velez RL, Freeman RB, Tsunoda SM. A review of interleukin-2 receptor antagonists in solid organ transplantation. Pharmacotherapy 1999: 19: 1127–1137.
- 12Ganschow R, Broering DC, Stuerenburg I, et al. First experience with basiliximab in pediatric liver graft recipients. Pediatr Transplant 2001: 5: 353–358.
- 13Kelly DA. The use of anti-interleukin-2 receptor antibodies in pediatric liver transplantation. Pediatr Transplant 2001: 5: 386–389.
- 14Ganschow R, Grabhorn E, Schulz A, et al. Long-term results of basiliximab induction immunosuppression in pediatric liver transplant recipients. Pediatr Transplant 2005: 9: 741–745.
- 15Goralczyk AD, Hauke N, Bari N, et al. Interleukin 2 receptor antagonists for liver transplant recipients: A systematic review and meta-analysis of controlled studies. Hepatology 2011: 54: 541–554.
- 16Aw MM, Taylor RM, Verma A, et al. Basiliximab (Simulect) for the treatment of steroid-resistant rejection in pediatric liver transpland recipients: A preliminary experience. Transplantation 2003: 75: 796–799.
- 17Togashi J, Sugawara Y, Tamura S, et al. Basiliximab as therapy for acute rejection after liver transplantation for hepatitis C virus cirrhosis. Biosci Trends 2011: 5: 57–60.
- 18Dhawan A. Etiology and prognosis of acute liver failure in children. Liver Transpl 2008: 14: S80–S84.
- 19Uemoto S, Inomata Y, Sakurai T, et al. Living donor liver transplantation for fulminant hepatic failure. Transplantation 2000: 70: 152–157.
- 20Sakamoto S, Haga H, Egawa H, et al. Living donor liver transplantation for acute liver failure in infants: The impact of unknown etiology. Pediatr Transplant 2008: 12: 167–173.
- 21Mohamed EL, Moghazy W, Ogura Y, et al. Pediatric living-donor liver transplantation for acute liver failure: Analysis of 57 cases. Transpl Int 2010: 23: 823–830.
- 22Kasahara M, Umeshita K, Inomata Y, Uemoto S; Japanese Liver Transplantation Society. Long-term outcomes of pediatric living donor liver transplantation in Japan: An analysis of more than 2200 cases listed in the registry of the Japanese Liver Transplantation Society. Am J Transplant 2013: 13: 1830–1839.
- 23Mahadeb P, Gras J, Sokal E, et al. Liver transplantation in children with fulminant hepatic failure: The UCL experience. Pediatr Transplant 2009: 13: 414–420.
- 24Heffron TG, Pillen T, Smallwood G, et al. Pediatric liver transplantation for acute liver failure at a single center: A 10-yr experience. Pediatr Transplant 2010: 14: 228–232.
- 25Strauss A, Grabhom E, Sornsakrin M, et al. Liver transplantation for fulminant hepatic failure in infancy: A single center experience. Pediatr Transplant 2009: 13: 838–842.
- 26Miloh T, Kerkar N, Parkar S, et al. Improved outcomes in pediatric liver transplantation for acute liver failure. Pediatr Transplant 2010: 14: 863–869.
- 27Demetris A, Batts K, Dhillon A, et al. Banff schema for grading liver allograft rejection: An international consensus document. Hepatology 1997: 25: 658–663.
- 28Demetris AJ, Adeyi O, Bellamy CO, et al. Liver biopsy interpretation for causes of late liver allograft dysfunction. Hepatology 2006: 44: 489–501.
- 29Yamada H, Kondou H, Kimura T, et al. Humoral immunity is involved in the development of pericentral fibrosis after pediatric live donor liver transplantation. Pediatr Transplant 2012: 16: 858–865.
- 30Saitoh A, Sakamoto S, Fukuda A, et al. A universal preemptive therapy for cytomegalovirus infections in children after live-donor liver transplantation. Transplantation 2011: 92: 930–935.
- 31Imadome K, Fukuda A, Kawano F, et al. Effective control of Epstein-Barr virus infection following pediatric liver transplantation by monitoring of viral DNA load and lymphocyte surface markers. Pediatr Transplant 2012: 16: 748–757.
- 32Su H, Lomghi MS, Wang P, et al. Human CD4+CD25(high)CD127(low/neg) regulatory T cells. Methods Mol Biol 2012: 806: 287–299.
- 33Kanazawa H, Sakamoto S, Fukuda A, et al. Living-donor liver transplantation with hyperreduced left lateral segment grafts: A single-center experience. Transplantation 2013: 95: 750–754.
- 34Devictor D, Tissieres P, Durand P, et al. Acute liver failure in neonates, infants and children. Expert Rev Gastroenterol Hepatol 2011: 5: 717–729.
- 35Lovell MO, Speeg KV, Halff GA, et al. Acute hepatic allograft rejection: A comparison of patients with and without centrilobular alterations during first rejection episode. Liver Transpl 2004: 10: 369–373.
- 36Sundaram SS, Melin-Aldana H, Neighbors K, Alonso EM. Histologic characteristics of late cellular rejection, significance of centrilobular injury, and long-term outcome in pediatric liver transplant recipients. Liver Transpl 2006: 12: 58–64.
- 37Abraham SC, Freese DK, Ishitani MB, et al. Significance of central perivenulitis in pediatric liver transplantation. Am J Surg Pathol 2008: 32: 1479–1488.
- 38Martin SR, Russo P, Dubois J, Alvares F. Centrilobular fibrosis in long-term follow-up of pediatric liver transplant recipients. Transplantation 2002: 74: 828–836.
- 39Tsujimura S, Saito K, Nakayamada S, et al. Transcriptional regulation of multidrug resistance-1 gene by interleukin-2 in lymphocytes. Genes Cells 2004: 9: 1265–1273.
- 40Creed TJ, Probert CS, Norman MN, et al. Basiliximab for the treatment of steroid-resistant ulcerative colitis: Further experience in moderate and severe disease. Aliment Pharmacol Ther 2006: 23: 1435–1442.
- 41Briem-Richter A, Leuschner A, Haag F, et al. Cytokine concentrations and regulatory T cells in living donor and deceased donor liver transplant recipients. Pediatr Transplant 2013: 17: 185–190.
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