Ann Hepatobiliary Pancreat Surg.  2020 May;24(2):216-220. 10.14701/ahbps.2020.24.2.216.

Effect of everolimus rescue therapy for acute cellular rejection following pediatric living donor liver transplantation: Report of one case

Affiliations
  • 1Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine
  • 2Division of Pediatric Surgery, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine
  • 3Department of Pediatrics, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea

Abstract

Acute cellular rejection (ACR) after pediatric living donor liver transplantation (LDLT) is often curable with steroid pulse therapy, but a few pediatric patients show steroid-resistant ACR, which is difficult to control. We report the effect of everolimus as a rescue therapy for ACR in a case of pediatric LDLT. The patient was a 11-year-old girl who was admitted due to subacute liver failure of unknown cause. LDLT operation using a modified right liver graft from her mother was performed. The graft-recipient weight ratio was 1.30. The explant liver showed massive hepatic necrosis. The patient recovered uneventfully with immunosuppression using tacrolimus and low-dose steroid. However, at postoperative day (POD) 20, the liver enzyme levels began to increase. The first liver biopsy taken at POD 25 showed moderate ACR with rejection activity index (RAI) score of 7. At that time, steroid pulse therapy was performed, but the patient did not respond and the liver enzyme levels increased further. The second liver biopsy taken at POD 40 showed moderate ACR with RAI score of 7. At this time, everolimus was administered, and soon after that, liver enzyme levels had gradually improved. Currently, the patient is doing well for 44 months to date without any abnormal findings. The maintenance target trough concentrations were tacrolimus 5 ng/ml and everolimus 3 ng/ml. Our case demonstrated the effect of rescue therapy using everolimus for ACR following pediatric LDLT. Further studies are needed to assess the role of everolimus in pediatric liver transplant recipients suffering from ACR.

Keyword

Acute cellular rejection; Rescue therapy; Immunosuppression; Everolimus; Sirolimus

Figure

  • Fig. 1 Pretransplant computed tomography finding. The liver was shrunken and liver perfusion was impaired, suggesting a failing liver.

  • Fig. 2 Posttransplant findings. (A) Computed tomography scan taken 7 days after transplantation showed no abnormal findings. (B) Intraoperative cholangiogram showed uneventful duct-to-duct anastomosis.

  • Fig. 3 Gross photograph of the explant liver. Massive hepatic necrosis was visible.

  • Fig. 4 Posttransplant computed tomography findings. Computed tomography scan taken 49 days after transplantation showed swelling of the liver graft, suggesting acute rejection.

  • Fig. 5 Serial changes of clinical sequences around the episode of acute cellular rejection. ALT, alanine aminotransferase; Bx, liver biopsy; RAI, rejection activity index; ACR, acute cellular rejection; FK, tacrolimus; EVR, everolimus.


Cited by  1 articles

Whole liver deceased donor liver transplantation for pediatric recipients: single-center experience for 20 years
Jung-Man Namgoong, Shin Hwang, Dae-Yeon Kim, Tae-Yong Ha, Gi-Won Song, Dong-Hwan Jung, Gil-Chun Park, Kyung Mo Kim, Seak Hee Oh
Korean J Transplant. 2020;34(4):249-256.    doi: 10.4285/kjt.20.0036.


Reference

1. Calne RY, Collier DS, Lim S, Pollard SG, Samaan A, White DJ, et al. 1989; Rapamycin for immunosuppression in organ allografting. Lancet. 2:227. DOI: 10.1016/S0140-6736(89)90417-0. PMID: 2568561.
Article
2. Flanagan WM, Corthésy B, Bram RJ, Crabtree GR. 1991; Nuclear association of a T-cell transcription factor blocked by FK-506 and cyclosporin A. Nature. 352:803–807. DOI: 10.1038/352803a0. PMID: 1715516.
Article
3. Aagaard-Tillery KM, Jelinek DF. 1994; Inhibition of human B lymphocyte cell cycle progression and differentiation by rapamycin. Cell Immunol. 156:493–507. DOI: 10.1006/cimm.1994.1193. PMID: 7517796.
Article
4. Holdaas H, Bentdal O, Pfeffer P, Mjørnstedt L, Solbu D, Midtvedt K. 2008; Early, abrupt conversion of de novo renal transplant patients from cyclosporine to everolimus: results of a pilot study. Clin Transplant. 22:366–371. DOI: 10.1111/j.1399-0012.2008.00795.x. PMID: 18279419.
Article
5. De Simone P, Nevens F, De Carlis L, Metselaar HJ, Beckebaum S, Saliba F, et al. H2304 Study Group. 2012; Everolimus with reduced tacrolimus improves renal function in de novo liver transplant recipients: a randomized controlled trial. Am J Transplant. 12:3008–3020. DOI: 10.1111/j.1600-6143.2012.04212.x. PMID: 22882750. PMCID: PMC3533764.
6. Nashan B. 2018; mTOR inhibition and clinical transplantation: liver. Transplantation. 102(2S Suppl 1):S19–S26. DOI: 10.1097/TP.0000000000001690. PMID: 28230639.
7. Levy G, Schmidli H, Punch J, Tuttle-Newhall E, Mayer D, Neuhaus P, et al. 2006; Safety, tolerability, and efficacy of everolimus in de novo liver transplant recipients: 12- and 36-month results. Liver Transpl. 12:1640–1648. DOI: 10.1002/lt.20707. PMID: 16598777.
Article
8. De Simone P, Carrai P, Precisi A, Petruccelli S, Baldoni L, Balzano E, et al. 2009; Conversion to everolimus monotherapy in maintenance liver transplantation: feasibility, safety, and impact on renal function. Transpl Int. 22:279–286. DOI: 10.1111/j.1432-2277.2008.00768.x. PMID: 19054383.
Article
9. Saliba F, De Simone P, Nevens F, De Carlis L, Metselaar HJ, Beckebaum S, et al. H2304 Study Group. 2013; Renal function at two years in liver transplant patients receiving everolimus: results of a randomized, multicenter study. Am J Transplant. 13:1734–1745. DOI: 10.1111/ajt.12280. PMID: 23714399.
Article
10. Fischer L, Saliba F, Kaiser GM, De Carlis L, Metselaar HJ, De Simone P, et al. H2304 Study Group. 2015; Three-year outcomes in de novo liver transplant patients receiving everolimus with reduced tacrolimus: follow-up results from a randomized, multicenter study. Transplantation. 99:1455–1462. DOI: 10.1097/TP.0000000000000555. PMID: 26151607.
11. Bilbao I, Dopazo C, Lazaro J, Castells L, Caralt M, Sapisochin G, et al. 2014; Multiple indications for everolimus after liver transplantation in current clinical practice. World J Transplant. 4:122–132. DOI: 10.5500/wjt.v4.i2.122. PMID: 25032101. PMCID: PMC4094947.
Article
12. Mártinez JM, Pulido LB, Bellido CB, Usero DD, Aguilar LT, Moreno JL, et al. 2010; Rescue immunosuppression with mammalian target of rapamycin inhibitor drugs in liver transplantation. Transplant Proc. 42:641–643. DOI: 10.1016/j.transproceed.2010.02.011. PMID: 20304212.
Article
13. Ueno T, Hiwatashi S, Saka R, Yamanaka H, Takama Y, Tazuke Y, et al. 2018; Everolimus rescue treatment for chronic rejection after pediatric living donor liver transplantation: 2 case reports. Transplant Proc. 50:2872–2876. DOI: 10.1016/j.transproceed.2018.03.079. PMID: 30318104.
Article
14. Kang SH, Hwang S, Ha TY, Song GW, Jung DH, Ahn CS, et al. 2019; Cross-sectional analysis of immunosuppressive regimens focused on everolimus after liver transplantation in a Korean high-volume transplantation center. Korean J Transplant. 33:98–105. DOI: 10.4285/jkstn.2019.33.4.98.
Article
15. Nielsen D, Briem-Richter A, Sornsakrin M, Fischer L, Nashan B, Ganschow R. 2011; The use of everolimus in pediatric liver transplant recipients: first experience in a single center. Pediatr Transplant. 15:510–514. DOI: 10.1111/j.1399-3046.2011.01515.x. PMID: 21696525.
Article
16. Ganschow R, Pape L, Sturm E, Bauer J, Melter M, Gerner P, et al. 2013; Growing experience with mTOR inhibitors in pediatric solid organ transplantation. Pediatr Transplant. 17:694–706. DOI: 10.1111/petr.12147. PMID: 24004351.
Article
17. Dumortier J, Couchonnal E, Lacaille F, Rivet C, Debray D, Boillot O, et al. 2019; mTOR inhibitors in pediatric liver transplant recipients. Clin Res Hepatol Gastroenterol. 43:403–409. DOI: 10.1016/j.clinre.2018.11.010. PMID: 30528864.
Article
18. Ganschow R, Ericzon BG, Dhawan A, Sharif K, Martzloff ED, Rauer B, et al. 2017; Everolimus and reduced calcineurin inhibitor therapy in pediatric liver transplant recipients: results from a multicenter, prospective study. Pediatr Transplant. 21. DOI: 10.1111/petr.13024. PMID: 28714558.
Article
19. Lehmkuhl HB, Mai D, Dandel M, Knosalla C, Hiemann NE, Grauhan O, et al. 2007; Observational study with everolimus (Certican) in combination with low-dose cyclosporine in de novo heart transplant recipients. J Heart Lung Transplant. 26:700–704. DOI: 10.1016/j.healun.2007.02.008. PMID: 17613400.
Article
20. Pascual J, Boletis IN, Campistol JM. 2006; Everolimus (Certican) in renal transplantation: a review of clinical trial data, current usage, and future directions. Transplant Rev. 20:1–18. DOI: 10.1016/j.trre.2005.10.005.
Article
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