Pediatric liver transplantation in Uzbekistan: first clinical case and outcome analysis

Background. Liver transplantation (LT) remains the only life-saving option for children with end-stage liver disease. In Uzbekistan, a national LT program was launched in 2018; however, pediatric LT had not been performed until recently.

Objective: to report the fi rst documented case of related pediatric LT in the Republic of Uzbekistan and to highlight key aspects of postoperative management, including rejection crises, recurrent autoimmune hepatitis (AIH), and the innovative use of bortezomib for treating steroid-resistant rejection.

Materials and methods. A 15-year-old patient with liver cirrhosis secondary to AIH was selected for transplantation. The right hepatic lobe from a living donor was transplanted following comprehensive preoperative evaluation and preparation. The procedure involved surgical intervention followed by a multistage postoperative treatment protocol.

Results. The transplant procedure was successful. However, in the early postoperative period, the patient developed a rejection crisis that proved resistant to standard therapy with glucocorticosteroids and antithymocyte globulin. Subsequent evaluation revealed a recurrent AIH. Bortezomib was administered as part of the therapeutic strategy, leading to normalization of laboratory parameters and restoration of graft function.

Conclusion. This fi rst case of pediatric LT in Uzbekistan demonstrates the feasibility of performing complex surgical interventions and managing challenging postoperative complications. The use of bortezomib for steroid-resistant rejection associated with AIH highlights a potentially promising therapeutic approach. These results mark an important step forward in the development of transplant care in the country.

1. Gautier SV, Tsiroulnikova OM, Moysyuk YG, Akhaladze DG, Tsiroulnikova IE, Silina OV et al. Liver transplantation in children: six-year experience analysis. Russian Journal of Transplantology and Artificial Organs. 2014; 16 (3): 54–62. (In Russ.). https://doi.org/10.15825/1995-1191-2014-3-54-62.

2. Smith SK, Miloh T. Pediatric Liver Transplantation. Clin Liver Dis. 2022; 26 (3): 521–535. https://doi.org/10.1016/j.cld.2022.03.010.

3. Otte JB. History of pediatric liver transplantation. Where are we coming from? Where do we stand? Pediatr Transplant. 2002; 6 (5): 378–387. https://doi.org/10.1034/j.1399-3046.2002.01082.x.

4. Spada M, Riva S, Maggiore G, Cintorino D, Gridelli B. Pediatric liver transplantation. World J Gastroenterol. 2009; 15 (6): 648–674. https://doi.org/10.3748/wjg.15.648.

5. Martin BE, Ong EG. Pediatric liver transplantation: an overview. Pediatr Child Health. 2017; 27 (12): 546–551. https://doi.org/10.1016/j.paed.2017.07.008.

6. Strong RW, Lynch SV, Ong TH, Matsunami H, Koido Y, Balderson GA. Successful liver transplantation from a living donor to her son. N Engl J Med. 1990 May 24; 322 (21): 1505–1507. https://doi.org/10.1056/NEJM199005243222106.

7. Raia S, Nery JR, Mies S. Liver transplantation from live donors. Lancet. 1989 Aug 26; 2 (8661): 497. https://doi.org/10.1016/s0140-6736(89)92101-6.

8. Mogul DB, Luo X, Bowring MG, Chow EK, Massie AB, Schwarz KB et al. Fifteen-Year Trends in Pediatric Liver Transplants: Split, Whole Deceased, and Living Donor Grafts. J Pediatr. 2018 May; 196: 148–153.e2. https://doi.org/10.1016/j.jpeds.2017.11.015.

9. Semash K, Dzhanbekov T, Akbarov M, Mirolimov M, Usmonov A, Razzokov N et al. Implementation of a living donor liver transplantation program in the Republic of Uzbekistan: a report of the first 40 cases. Clin Transplant Res. 2024; 38 (2): 116–127. https://doi.org/10.4285/ctr.24.0013.

10. Porkhanov VA, Ismailov SI, Nazyrov FG, Popov AY, Babadzhanov AK, Lishchenko AN et al. Rodstvennaya transplantatsiya pecheni v Respublike Uzbekistan: nyneshnee sostoyanie i perspektivy razvitiya [Living related liver transplantation in the Republic of Uzbekistan: current status and development prospects]. Khirurgiia (Mosk). 2023; (11): 34–46. https://doi.org/10.17116/hirurgia202311134.

11. Semash K. Evaluation and Management of Living Donors in the Setting of Living Donor Liver Transplant Program in the Republic of Uzbekistan. Exp Clin Transplant. 2024; 22 (9): 664–674. https://doi.org/10.6002/ect.2024.0148.

12. Montano-Loza AJ, Ronca V, Ebadi M, Hansen BE, Hirschfield G, Elwir S et al. International Autoimmune Hepatitis Group (IAIHG). Risk factors and outcomes associated with recurrent autoimmune hepatitis following liver transplantation. J Hepatol. 2022 Jul; 77 (1): 84–97. https://doi.org/10.1016/j.jhep.2022.01.022.

13. Patel YA, Henson JB, Wilder JM, Zheng J, Chow SC, Berg CL et al. The impact of human leukocyte antigen donor and recipient serotyping and matching on liver transplant graft failure in primary sclerosing cholangitis, autoimmune hepatitis, and primary biliary cholangitis. Clin Transplant. 2018 Oct; 32 (10): e13388. https://doi.org/10.1111/ctr.13388.

14. Harputluoglu M, Caliskan AR, Akbulut S. Autoimmune hepatitis and liver transplantation: Indications, and recurrent and de novo autoimmune hepatitis. World J Transplant. 2022 Mar 18; 12 (3): 59–64. https://doi.org/10.5500/wjt.v12.i3.59.

15. Montano-Loza AJ, Rodríguez-Perálvarez ML, Pageaux GP, Sanchez-Fueyo A, Feng S. Liver transplantation immunology: Immunosuppression, rejection, and immunomodulation. J Hepatol. 2023 Jun; 78 (6): 1199– 1215. https://doi.org/10.1016/j.jhep.2023.01.030.

16. Mercado LA, Gil-Lopez F, Chirila RM, Harnois DM. Autoimmune Hepatitis: A Diagnostic and Therapeutic Overview. Diagnostics (Basel). 2024 Feb 9; 14 (4): 382. https://doi.org/10.3390/diagnostics14040382.

17. Tajima T, Hata K, Okajima H, Nishikori M, Yasuchika K, Kusakabe J et al. Bortezomib Against Refractory Antibody-Mediated Rejection After ABO-Incompatible Living-Donor Liver Transplantation: Dramatic Effect in Acute-Phase? Transplant Direct. 2019 Sep 19; 5 (10): e491. https://doi.org/10.1097/TXD.0000000000000932.

18. Lee CF, Eldeen FZ, Chan KM, Wu TH, Soong RS, Wu TJ et al. Bortezomib is effective to treat acute humoral rejection after liver transplantation. Transplant Proc. 2012 Mar; 44 (2): 529–531. https://doi.org/10.1016/j.transproceed.2012.01.051.

19. Jiang H, Guo H, Yang B, Zhao Y, Wei L, Chen Z, Chen D. Acute Antibody-Mediated Rejection in Liver Transplant Recipients with Autoimmune Liver Disease: A Clinical and Pathologic Study of 4 Cases. J Pers Med. 2023; 13 (1): 41. https://doi.org/10.3390/jpm13010041.

20. Marubashi S, Dono K, Nagano H, Asaoka T, Hama N, Kobayashi S et al. Postoperative hyperbilirubinemia and graft outcome in living donor liver transplantation. Liver Transpl. 2007 Nov; 13 (11): 1538–1544. https://doi.org/10.1002/lt.21345.