Fung, JJ

Jain, A

Kashyap, R

Kosmach-Park, B

Mazariegos, G

Reyes, J

Starzl, TE

English

PubMed

Name not available

Pediatric liver transplantation in 808 consecutive children: 20-years experience from a single center

D-Scholarship@Pitt

ELSEVIER LIVER Pediatric Liver Transplantation in 808 Consecutive Children: 20-Years Experience From A Single Center A. Jain, G. Mazariegos, R. Kashyap, B. Kosmach-Park, T.E. Starzl, J.J. Fung, and J. Reyes SURVIVAL for children is significantly higher than for adults after liver transplantation (LTx).l A center· specific 20·year retrospective analysis of all pediatric trans· plant recipients was implemented to determine patient and graft survival, graft survival, and differences in survival related to immunosuppressive protocols. MATERIALS AND METHODS From March 1981 to April 1998, 808 children received liver transplants at the Children's Hospital of Pittsburgh. All patients were followed until March 2001, with a mean follow·up of 12.2 ::<:: 3.9 years (median = 12.6; range = 2.9 to 20). There were 405 female (50.2%) and 403 male (49.8%) pediatric recipients. The mean age at transplant was 5.3 ::': 4.9 years (mean = 3.3; range 0.04 to 17.95) with 285 children (25.3%) being less than 2 years of age at transplant. Cyclosporine (CsA)-based immunosuppression was used prior to November 1989 in 482 children (50.7%) and the ~1MM ~ ~ -.......:::.. .' --..... Cyclosporioe Cn 482) ___ Tacrolilnus (0 = 326) --.- Overall Pt. Survival subsequent 326 recipients (40.3%) were treated with tacrolimus-based immunosuppression. RESULTS Patient Survival Overall patient survival at 1, 5, 10, 15, and 20 years was 77.1 %, 72.6%, 69.4%, 65.8%, and 64.4%, respectively (Fig 1). A significant difference in survival was seen in CsA-From the Children's Hospital of Pittsburgh and the Thomas E. Starzl Transplantation Institute, Department of Surgery (A.J., G.M., R.K., T.E.S., J.J.F., J.R.) and School of Pharmaceutical Sciences (A.J.), University of Pittsburgh Medical Center, Pitts-burgh, Pennsylvania. Address reprint requests to Jorge Reyes, MD, Thomas E. Starzl Transplantation Institute, C~lildrenDs Hospital of Pitts-burgh, Room 4A, 470, 3705 Fifth Avenue, Pittsburgh, PA 15213. -P=O.OOOI ~ ~ ~ ~ ~ ~ ~ ~ ~ y ~ ~ ~ ~ ~ ~ ~ Years Post-Transplant Fig 1. Patient survival under cyclosporine and tacrolimus immunosuppression. © 2002 by ElseVier SCience Inc. 655 Avenue of the Americas, New York, NY 10010 Transplantation Proceedings, 34, 1955-1957 (2002) 0041-1345/02/$-see front matter PII S0041-1345(02)03136-6 1955 1956 JAIN, MAZARIEGOS, KASHYAP ET AL 25 t? 20 il) - 15 ('j lID Total 0::: ~ . • Cyclosporine >-. 10 ......., • TacroliInus .--('j 5 ...... H 0 ~ 0 0.25 2 4 6 8 10 12 14 16 18 20 Years Post-Transplant Fig 2. Overall morality rate over time under cyclosporine and tacrolimus immunosuppression. based immunosuppression (71.2%, 68.1%, 65.4%, and 61 %) versus tacrolimus-based immunosuppression (85.8%, 84.7%,83.3%, and 82.9%) at 1, 3,5, and 10 years, respec-tively (P = .0001) (Fig 2). The maximum difference in the risk of death was observed in the first 3 months posttrans-plant, 22.8% under esA versus 9.5% under tacrolimus. After 3 months, the survival at 10 years was 78.6% under esA versus 91.5% under tacrolimus, a difference of 12.9%. Causes of Death A total of 258 children (32%) died during the follow-up period, with 55.4% of deaths occurring within the first 3 months posttransplant. Of the mortalities, 203 recipients received esA-based immunosuppression, and 55 recipients were treated with tacrolimus. The most common cause of death was infection (43%). The mean annual death rate beyond 2 years posttransplant was 0.47% with the mean annual death rate for patients receiving tacrolimus-based immunosuppression being significantly lower than those receiving esA-based immunosuppression (0.14% vs 0.8%; P = .001). The annual death rate for patients under esA and tacrolimus-based immunosuppression is shown in Fig 2. The difference in the death rate between the immunosup-pressive protocols was observed at all time points. The cumulative death rate at 1, 3, and 12 months posttransplant under esA was 16.3%, 22.6%, and 28.8%, respectively, and for tacrolimus-treated patients was 6.4%, 9.5%, and 14%, respectively. Graft Survival Patient deaths or retransplantations were considered as graft loss. Graft survival at 1. 5. 10, 15. and 20 years was (16,6G'O. 60%. 57%. 52.3%. and 37.9%, respectivelv. Graft survival LInder CsA versus tacrolimus-based immunosup-rresslOn was similar to patient survival With a highlv signif-Icant difference \ P = .0001) at 12 years posttransplant. Retransplantation Two hundred three children (25.1 %) required a second liver transplant. Additionally, 40 children required a third graft, six received four grafts, and one child received five liver transplants. All seven children who received four or more grafts died. Hepatic artery thrombosis was the most common indication for a second allograft under both esA-and tacrolimus-based immunosuppression, with an inci-dence of 33.4% (n=68) of all retransplantations. The second most common reason for retransplantation was rejection, both acute and chronic, with 54 patients (26.6%) requiring another graft. Retransplantation was required in six patients (2.9%) with acute rejection and 46 patients (22.6%) with chronic rejection. Interestingly, all retrans-plantations for acute or chronic rejection were performed in patients who were treated with esA-based immunosup-pression and none under tacrolimus. Primary nonfunction was the third most common indica-tion for retransplantation and was seen in 34 patients (16.7%). Of these patients, 19 (9.3%) were treated with esA and 15 (7.3%) were treated with tacrolimus. Addi-tional reasons for retransplantation included biliary stric-ture, posttransplantation lymphoproliferative disorder, and others. DISCUSSION A 20-year overall actuarial patient survival of 64..+% is reported here. representing the largest pediatric liver trans-plant experitnce with the longest follow-up from a singk center. The most significant factor affecting survival in this experience was a change in immunosuppressive protocols from CsA-based immunosuppression in the 1980s. with a survival of hI % at 10 years. to tacrolimus-based immuno-suppression resulting in an R3% survival at 10 years. This analysis reports the almost complete absence of graft loss from either acute or chronic rejection under tacroJimus. which is remarkable conSIdering the incidence under esA is 20-YEAR PEDIATRIC LIVER EXPERIENCE 11 S in a 20-year follow-up. Over u decade ago. observa-tions from this institutIon supported the findings of a reduced rate of acute rejection as well as a decreased severity of rejection in patients receiving tacrolimus. 2.3 Additionally. the ability of tacrolimus to reverse acute and chronic rejection and act as a rescue agent for patients failing treatment with CsA provided a better understanding of the process of rejection and its treatmen t as well as the clinical limits of failure. At this institution, nearly 25% of children under CsA-based immunosuppression have been converted to tacrolimus with many of the grafts rescued from acute and chronic rejection during the last decade. 4 Similar advantages of tacrolimus in pediatric transplanta-tion have been published from our center and by others5 --7 Nearly 80% of pediatric patients are now maintained on only low-dose tacrolimus.K The virtual absence of chronic rejection in adult liver transplant recipients following a review of over 5000 liver biopsies from more than 1200 patients with a mean follow-up of 6 years has been previ-ously reported9 Hepatitis Band C viruses, primary biliary cirrhosis, autoimmune hepatitis, and primary sclerosing cholangitis were found to be risk factors for the develop-ment of chronic rejection after liver transplantation. Fortu-nately, these liver diseases as indications for transplantation are extremely rare in the pediatric population. Chronic rejection in pediatric liver transplant recipients is usually a result of treatment for life-threatening infection PTLD or noncompliance. CONCLUSION The 20-year actuarial survival for pediatric liver transplant recipients is 64% in a series of 808 children. Infection 1957 remains thc most common cause of death. Retransplanta-tion is most commonly indicated for hepatic artery throm-bosis and primary nonfunction. Survival following the in-troduction of tacrolimus-based immunosuppression has increased hy 14 to 21 % at I year (85% vs 71.2% I and 12 years (82.9% vs 61 %) posttransplant. The incrcased sur-vival rate of our program may reflect improvements in surgical techniques. bettcr donor and recipient selection, and advances in posttransplant medical management. How-ever. in our experience. increased survival can be attributed to the almost total absence of graft loss due to acute or chronic rejection in up to a 12-year follow-up, which reflects the immunologic advantage of tacrolimus-bK~sed immuno-suppression. REFERENCES 1. Jain A, Reyes J, Kashyap R, et al: Ann Surg 232:490,2000 2. Jain AB, Fung lJ, Todo S, et a1: Transplant Proc 23:928. 1991 3. Tzakis AG, Fung JJ, Todo S. et al: Transplant Proc 23:924, 1991 4. Reyes J. Jain AB, Mazariegos G, et al: Transplantation 69:2573, 2000 5. Jain A, Mazariegos G, Kashyap R. et al: Transplantation 70:617. 2000 6. McDiannid SV, Busuttil RW, Ascher NL, et al: Transplanta-tion 59:530. 1995 7. Reyes J, Mazariegos GV: Surgical Clinics of North America 79:163, 1999 8. Jain AB, Mazariegos G, Kashap R, et al: Ped Transplantation 5:93,2001 9. Jain A, Demetris A, Kashyap R, et al: Liver Transplantation 7:623, 2001 

Pediatric liver transplantation in 808 consecutive children: 20-Years experience from a single center

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Pediatric liver transplantation in 808 consecutive children: 20-Years experience from a single center

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