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Indian Pediatrics 1999; 36:353-355 

Liver Transplantation in Children

The successful development of pediatric liver transplantation has dramatically changed the prognosis for many children dying of end stage liver failure and is now an accepted therapy for this condition in developed countries(1). The indications for transplantation include acute and chronic liver failure, inherited metabolic liver disease and unresectable hepatic tumors. The major indication worldwide is for children with biliary atresia who have had an unsuccessful Kasai portoenterostomy, accounting for 76% of children transplanted under the age of 2 years in Europe and America(2). Fulminant hepatic failure secondary to viral hepatitis or poisoning is now an increasing indication and approximately 10% of transplants in Europe are performed for this reason(1).

There has peen a dramatic increase in the survival rate throughout the 1990's with most International Centers reporting one year actuarial survival rates of between 85-90% and a 5-8 year survival of 75-80%(3-5). Many elements have contributed to the improved survival post liver transplantation. These include a better understanding of pre-operative management such as the treatment of hepatic complications and the importance of intensive nutritional support(3). The development of better preservative solutions and surgical techniques, such as reduction hepatectomy, has extended liver transplantation to infants under the age of one year and weighing less than 0 kg, effectively reducing the waiting list mortality from 25% to 5%(6).

Shortages in the organ donor pool have been addressed by innovative surgical techniques which include the development of split liver transplantation and of living related liver transplantation(7-9). Auxiliary liver transplantation (in which only part of the recipient's liver is replaced) may have a role in the transplantation of acute liver failure or transplantation for metabolic disease in those with a normal liver and hepatic enzyme deficiencies such as Crigler-Najjar Type I(10).

The initially high morbidity and comp]ication rate post transplant has also reduced following increased medical and surgical experience. Complications such as. primary graft non function are now almost non existent(11), and the re-transplantation rates in children have fallen( 12). Increased experience with reduction hepatectomies and split liver transplantation has reduced the originally high rate of vascular thrombosis, particularly hepatic artery thrombosis in children(13). The difficult problem of acute and chronic rejection, which historically is less common in children than in adults(14) has improved following advances in immunosuppression with drugs which are more easily absorbed such as cyclosporin microemulsion (Neoral)(15) or more potent such as Tacrolimus which has reduced the incidence of chronic rejection(16).

As long term survival increases, attention has now focused on the quality of life achieved by children undergoing transplantation. Long term studies in children and adolescents have demonstrated the striking nutritional rehabilitation achieved following successful liver transplantation (17,18). Detailed data demonstrate that weight, fat stores and protein muscle mass recover within 12 months of transp]antation(3) while normal height velocity is dependent on the degree of pre-trans- plant malnutrition and the dosage of steroid therapy(19).

More importantly there is clear maintenance of psychosocial development both physically and intellectually(1,20,21). Many studies have demonstrated normal, if delayed, pubertal development and growth spurts have been clearly documented and successful pregnancies reported(16,22).

Some problems remain, particularly related to the long term effects of immunosuppression. The short term effects of steroids and cyclosporin are well documented and include hypertension, neurotoxicity and nephrotoxicity(1,16). The long term effect of immunosuppression on the. development of post transplant lymphoproliferative disease and other tumors remains unknown(23).

The success of pediatric liver transplantation in developed countries has increased the awareness and need for such procedures in the
. developing world. Mehrotra and Yachha report in this issue that 79% of babies with biliary atresia in their center require transplantation based on internationally accepted criteria(24). Sixty-one per cent of older children with cirrhosis and 67% with fulminant hepatic failure fulfill criteria for liver transplantation(24). This paper clearly establishes the need for liver transplantation in India.

In order for liver transplantation to be practical in a developing country like India, it is essential to have the ability to develop programs for both living related liver transplantation and cadaveric liver transplantation. An appropriate brain death law is already in place, but, sufficient professional and public education is needed to develop organ donation. It is essential to have the necessary re- sources to harvest organs from a wide geo- graphical area and to develop the surgical, medical and multidisciplinary support necessary for the success of those procedures. Also, there is a need for professional education with regard to early and appropriate referral to optimize survival. Ideally liver transplantation should begin in a single national center in order to consolidate both resources and experience.

D.A. Kelly,
Reader in Pediatric Hepatology,
Birmingham Children's Hospital,
Birmingham B4 6NH, and
University of Birmingham,
Edgbaston, Birmingham,
Anupam Sibal,
Consultant Pediatric Gastroenterologist
and Hepatologist,
Department of Multi Organ Transplantation,
Indraprastha Apollo Hospital,

New Delhi, India.


1. Kelly DA. Current results and evolving indications. for liver transplantation in children. J Pediatr Gastroenterol Nutr 1998; 27: 214-221.

2. Belle SH, Beringer KC, Detre KM. An update on liver transplantation' in the United-states:- Recipient characteristics and outcome. Clin Transp11995; 19-33.

3. Beatli SV, Brook GA, Cash AJ, McMaster P, Mayer AD, Buckels JAC. Successful liver transplantation in babies under 1 year. BMJ 1993; 307: 825-828.

4. Eckhoff DE, D' Alessandro AM, Knechtle SJ, Pirsch JD, Ploeg RJ, Judd RH, et al. 100 consecutive liver transplants in infants and children: An 8-year .experience. J Pediatrc Surg ]994;29: 1135-1140.

5. Yandza T, Gauthier F, Valayer J. Lessons from the first 100 liver transplantations in children at Bicetre Hospital. 1994; 29: 905-911.

6. de Ville de Goyet J, Hausleithner V, Reding R, Lerut J, Janseen M, Otte JB. Impact of innovative techniques on the waiting list and results in pediatric liver transplantation. Transplantation , 1993; 56; 1130-1136.

7. Inomata Y, Tanaka K, Okajima H, Uemoto S, Ozaki N, Egawa H, et al. Living related liver transplantation for children younger than one year old. Eur J Pediatr Surg 1996; 6: 148-151.

8. Bonati H, Muiesa'n P, Connelly S, Baker A, Mieli-Vergani G, Gibbs P, et al. Hepatic transplantation in children under 3 months of age: A single centre's experience. J Pediatr Surg 1997; 32: 486-488.

9. Inomata Y, Oike F, Okamoto S, Uemoto S, Asonuma K, Egwa H, et al. Impact of the development of a liver transplant program on the treatment of biliary atresia in an institution in Japan. J Pediatr Surg 1997; 32: 1201-1205.

10. Rela M, Muiessan P, Andreani P, Gibbs P, Mieli-Vergani G, Mowat AP, et al. Auxiliary liver transplantation for metabolic diseases. Trans Proc 1997; 29: 444-445.

11. Talbot D, Achilleos OA, Gunson BK, McKiernan P, Beath S, Kelly DA, et al. Progress in pediatric liver transplantation: The Birmingham experience. J Pediatr Surg 1997; 32: 710-713.

12. Achilleos OA, Talbot D, Mirza DF, Gunson BK, Freeman JW, Mayer AD, et al. Retransplantation rate in 200 pediatric liver transplants. The Birmingham experience. Liver Trans Surg 1995; 1: 430-435.

13. Rela M, Muiesan P, Bhatnagar V, Baker A, Mowat AP, Mieli-Verganier, et al. Hepatic artery thrombosis after liver transplantation in children under 5 years of age. Transplantation 1996; 61: 1355-1357.

14. Murphy MS, Harrison R, Davies, Buckels JA, Mayer AD, Hubscher S, et al. Risk factors for liver rejection: Evidence to suggest enhanced allograft tolerance in infancy. Arch Dis Child 1996; 75: 502-506.

15. Van Mourik, I, Vilca Melendez H, Thomson M, Mieli-Vergani G, Heaton N, Kelly DA. Efficacy of Neoral in the immediate post- operative period in children post Liver transplantation. Liver Transplant Surg 1998; 6: 491- 498.

16. Cox KL, Freese D K. Tacrolimus (FK506): The pros and cons of its use as an immunosuppressant in pediatric liver transplantation. Clin Invest Med 1996; 19: 389-392.

17. Codoner-Franch P, Bernard 0, Alvarez F. Long term follow up of growth in height after successful liver transplantation. J Pediatr 1994; 124: 368-373.

18. Holt RI, Broide E, Buchanan CR, Miell JP, Baker AJ, Mowat AP, et al. Orthotopic liver transplantation reverses the adverse nutritional changes of end stage liver disease in children. Am J Clin Nutr 1997; 65: 534-542.

19. McKiernan PJ, Penitain GD, Johnson T, Buckels JA, Mayer AD, Kelly DA. Catch up, growth in children following orthotopic liver transplantation. Hepatol 1992; 16: 567.

20. Beath SV; Cash AJ, Brook GA, Mayer AD, Buckels JAC, Kelly DA. Long term outcome of liver transplantation (L Tx) in babies aged less than 12 months. J Pediatr Gastroenterol Nutr 1997; 24: 485.

21. Stone RD, Beasley PJ, Treacey SJ, Twente A W, Vacanti JP. Children and families can achieve normal psychological adjustment and a good quality of life following pediatric liver transplantation: A long term study. Trans Proc 1997; 29: 1571-1572.

22. Laifer SA, Guido RS. Reproductive function and outcome of pregnancy after liver transplantation in women. Mayo Clin Proc 1995; 70: 388-394.

23. Tzakis AG, Reyes J, Todo S, Nour B, Shapiro R, Jordan M, et al. Two year experience with FK506 in pediatric patients. Trans Proc 1993; 25: 619-216.

24. Mehrotra P, Yachha SK, Need for liver transplantation in Indian children. Indian Pediatr 1999;36: 357-362.


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