Liver Transplantation in Children Weighing Less Than 10 kg: Chilean Experience M. Uribe, A. Alba, B. Hunter, G. González, J. Godoy, M. Ferrario, E. Buckel, S. Cavallieri, C. Heine, R. Rebolledo, H. Auad, and C. Acuña ABSTRACT Background. Orthotopic liver transplantation is the treatment of choice for most terminal liver diseases in children. In small children (10 kg), this procedure is challenging and has special considerations. The aim of this study is to describe the experience of a Chilean liver transplantation program in this subgroup of patients. Methods. The liver transplant database of Hospital Luis Calvo Mackenna and Clinica Las Condes was reviewed. All children less than 10 kg undergoing liver transplantation between January 1994 and July 2011 were included. Patient and graft outcomes and main complications were analyzed. Results. We have performed 230 pediatric liver transplantations, 49 of them in 41 patients weighing less than 10 kg. The first indication for transplantation was biliary atresia in 25 patients (61%). A living related donor was used in 23 cases (51%). Actuarial survival was 75.7% at 1 year and 67.1% at 5 years. The main cause of death was infection, and the leading cause of graft loss was vascular complication. Discussion. Our transplant program includes 2 centers that perform more than 90% of pediatric liver transplantations in Chile, including public health pediatric patients from all around the country. Patients weighing less than 10 kg represent the most challenging group in pediatric liver transplantation due to higher rates of vascular and biliary complications and postoperative infections.
L
IVER TRANSPLANTATION (OLT) is the standard treatment for children with end-stage liver diseases.1 Results have improved in the last years due to advances in surgical techniques, new immunosuppressive drugs, and improved intensive care post-transplant management.2,3 Patients weighing less than 10 kg are a high-risk group, as they represent a real challenge due to surgical difficulties and post-transplant medical complications.4e7 Several studies have reported age as a factor influencing outcome,8 but body weight has proved to be a more important variable to consider.9e11 The aim of this study is to present the Chilean experience in transplanting children less than 10 kg in a 2-center pediatric liver program. PATIENTS AND METHODS A cross-sectional study was conducted between January 1994 and June 2011 from review of a liver transplant database in 2 centersdHospital Luis Calvo Mackenna (pediatric public hospital)
and Clinica Las Condes (private hospital)dincluding all children weighing less than 10 kg undergoing liver transplantation. Demographic characteristics, primary liver disease, and post-transplant complications were analyzed. Kaplan-Meier analysis was used to calculate patient and graft survival rates.
RESULTS
Our group has performed 230 pediatric liver transplantations, 49 of them in 41 patients weighing less than 10 kg. Twenty-two recipients were males (54%), with
From the Hospital Luis Calvo Mackenna (M.U., A.A., B.H., G.G., J.G., S.C., C.A.), Clínica Las Condes (M.F., E.B.), and Universidad de Chile (C.H., R.R., H.A.), Santiago, Chile. Address reprint requests to M. Uribe, MD, Liver Transplant Program, Hospital Luis Calvo MackennaeClínica las Condes, Lo Fontecilla 441, Las Condes, Santiago, Chile E-mail: muribem@ clc.cl
ª 2013 by Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710
0041-1345/13/$esee front matter http://dx.doi.org/10.1016/j.transproceed.2013.08.092
Transplantation Proceedings, 45, 3731e3733 (2013)
3731
3732
URIBE, ALBA, HUNTER ET AL
Table 1. Indications for Liver Transplantation in 41 Children Weighing Less Than 10 kg in the Pediatric Liver Transplant Program Hospital Luis Calvo Mackenna and Clínica Las Condes, 1994e2011 Diagnosis
n
Percentage
Biliary atresia Alagille syndrome Acute liver failure Neonatal hepatitis Retransplant Others
25 3 2 2 5 4
61 7 5 5 12 10
a mean age 1.3 0.5 years old and a median weight of 8.1 kg (range 4.8e10 kg). The principal indication for liver transplantation was biliary duct atresia in 25 patients (61%; Table 1). Twenty-three transplantations (51%) used living related donors (segments IIeIII), 11 complete liver, 10 reduced liver, and 1 split liver. All organs represented more than 1% of recipient body weight (Table 2). Fourteen patients presented vascular complications, 10 of them requiring surgical manage. Eight patients had biliary complications. Actuarial patient survival was 75.7% and 67.1% at 1 and 5 years, respectively (Fig 1). No differences were found between living related or deceased donor. Infections were the first cause of death, and organ failure was due in most of the cases to vascular complications. Five patients required retransplantation, 1 of them a second time, representing 15% of all the transplants performed in this group. Three (7.32%) children less than 10 kg transplanted died. Immunosuppression was based at the beginning on cyclosporine, azathioprine, and steroids and tacrolimus. Mycophenolic acid and steroids were used in the last 2 years. All rejection episodes were confirmed by liver biopsy and treated with bolus of methylprednisolone (20 mg/kg for three times in alternate days). It was impossible to conduct a multivariate analysis with such a limited number of cases. DISCUSSION
Our transplant program includes 2 centers that perform more than 90% of pediatric liver transplants in Chile, including public-health pediatric patients from around the country.12 As our expertise advances, new surgical techniques have been incorporated, and living related liver Table 2. Data of Recipient, Donor, and Graft Recipient age (y)
Recipient weight (kg)
Donor age (y)
Duration Donor of surgery Cold ischemia weight (kg) (h) time (min)
Median 1.5 8.8 27 62 6 90 Range (0.5e3.8) (4e10) (0.7e53) (8.5e85) (3.25e10) (1.45e450) 3.8 10 53 85 10 450
Fig 1. Actuarial survival of pediatric liver transplant patients, separated by weight. Hospital Luis Calvo Mackenna, Clinica Las Condes 1994e2011.
transplantation has increased over recent years.13,14 Patients weighing less than 10 kg represent the most challenging group in pediatric liver transplantation due to higher rates of vascular and biliary complications and postoperative infections. Malnutrition and growth retardation play a crucial role in the outcome of transplantation. Body weight and no age have been reported to reflect more accurately the clinical risk of these patients.11,15,16 One-year patient survival has been reported in the literature as 73% to 87%, and 5 and 10 years, 63% to 85%. Our results are comparable to most international series of high volume of transplants, with lower rates of retransplantation.15,16
REFERENCES 1. National Institutes of Health Consensus Development Conference Statement: liver transplantationdJune 20-23, 1983. Hepatology. 1984;4(1 Suppl):107Se110S. 2. Polak WG, Peeters PM, Slooff MJ. The evolution of surgical techniques in clinical liver transplantation. A review. Clin Transplant. 2009;23(4):546e564. 3. Williams R. Forty years of liver transplantation in the United Kingdomdreflections on challenges and achievements. Transplantation. 2009;87(9):1268e1272. 4. Otte JB, et al. Sequential treatment of biliary atresia with Kasai portoenterostomy and liver transplantation: a review. Hepatology. 1994;20(1 Pt 2):41Se48S. 5. Iglesias J, et al. Liver transplantation in infants weighing under 7 kilograms: management and outcome of PICU. Pediatr Transplant. 2004;8(3):228e232. 6. Arnon R, et al. Liver transplantation in children weighing 5 kg or less: analysis of the UNOS database. Pediatr Transplant. 15(6): 650e658. 7. Kaur S, et al. Outcome of live donor liver transplantation in Indian children with bodyweight
L
IVER TRANSPLANTATION (OLT) is the standard treatment for children with end-stage liver diseases.1 Results have improved in the last years due to advances in surgical techniques, new immunosuppressive drugs, and improved intensive care post-transplant management.2,3 Patients weighing less than 10 kg are a high-risk group, as they represent a real challenge due to surgical difficulties and post-transplant medical complications.4e7 Several studies have reported age as a factor influencing outcome,8 but body weight has proved to be a more important variable to consider.9e11 The aim of this study is to present the Chilean experience in transplanting children less than 10 kg in a 2-center pediatric liver program. PATIENTS AND METHODS A cross-sectional study was conducted between January 1994 and June 2011 from review of a liver transplant database in 2 centersdHospital Luis Calvo Mackenna (pediatric public hospital)
and Clinica Las Condes (private hospital)dincluding all children weighing less than 10 kg undergoing liver transplantation. Demographic characteristics, primary liver disease, and post-transplant complications were analyzed. Kaplan-Meier analysis was used to calculate patient and graft survival rates.
RESULTS
Our group has performed 230 pediatric liver transplantations, 49 of them in 41 patients weighing less than 10 kg. Twenty-two recipients were males (54%), with
From the Hospital Luis Calvo Mackenna (M.U., A.A., B.H., G.G., J.G., S.C., C.A.), Clínica Las Condes (M.F., E.B.), and Universidad de Chile (C.H., R.R., H.A.), Santiago, Chile. Address reprint requests to M. Uribe, MD, Liver Transplant Program, Hospital Luis Calvo MackennaeClínica las Condes, Lo Fontecilla 441, Las Condes, Santiago, Chile E-mail: muribem@ clc.cl
ª 2013 by Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710
0041-1345/13/$esee front matter http://dx.doi.org/10.1016/j.transproceed.2013.08.092
Transplantation Proceedings, 45, 3731e3733 (2013)
3731
3732
URIBE, ALBA, HUNTER ET AL
Table 1. Indications for Liver Transplantation in 41 Children Weighing Less Than 10 kg in the Pediatric Liver Transplant Program Hospital Luis Calvo Mackenna and Clínica Las Condes, 1994e2011 Diagnosis
n
Percentage
Biliary atresia Alagille syndrome Acute liver failure Neonatal hepatitis Retransplant Others
25 3 2 2 5 4
61 7 5 5 12 10
a mean age 1.3 0.5 years old and a median weight of 8.1 kg (range 4.8e10 kg). The principal indication for liver transplantation was biliary duct atresia in 25 patients (61%; Table 1). Twenty-three transplantations (51%) used living related donors (segments IIeIII), 11 complete liver, 10 reduced liver, and 1 split liver. All organs represented more than 1% of recipient body weight (Table 2). Fourteen patients presented vascular complications, 10 of them requiring surgical manage. Eight patients had biliary complications. Actuarial patient survival was 75.7% and 67.1% at 1 and 5 years, respectively (Fig 1). No differences were found between living related or deceased donor. Infections were the first cause of death, and organ failure was due in most of the cases to vascular complications. Five patients required retransplantation, 1 of them a second time, representing 15% of all the transplants performed in this group. Three (7.32%) children less than 10 kg transplanted died. Immunosuppression was based at the beginning on cyclosporine, azathioprine, and steroids and tacrolimus. Mycophenolic acid and steroids were used in the last 2 years. All rejection episodes were confirmed by liver biopsy and treated with bolus of methylprednisolone (20 mg/kg for three times in alternate days). It was impossible to conduct a multivariate analysis with such a limited number of cases. DISCUSSION
Our transplant program includes 2 centers that perform more than 90% of pediatric liver transplants in Chile, including public-health pediatric patients from around the country.12 As our expertise advances, new surgical techniques have been incorporated, and living related liver Table 2. Data of Recipient, Donor, and Graft Recipient age (y)
Recipient weight (kg)
Donor age (y)
Duration Donor of surgery Cold ischemia weight (kg) (h) time (min)
Median 1.5 8.8 27 62 6 90 Range (0.5e3.8) (4e10) (0.7e53) (8.5e85) (3.25e10) (1.45e450) 3.8 10 53 85 10 450
Fig 1. Actuarial survival of pediatric liver transplant patients, separated by weight. Hospital Luis Calvo Mackenna, Clinica Las Condes 1994e2011.
transplantation has increased over recent years.13,14 Patients weighing less than 10 kg represent the most challenging group in pediatric liver transplantation due to higher rates of vascular and biliary complications and postoperative infections. Malnutrition and growth retardation play a crucial role in the outcome of transplantation. Body weight and no age have been reported to reflect more accurately the clinical risk of these patients.11,15,16 One-year patient survival has been reported in the literature as 73% to 87%, and 5 and 10 years, 63% to 85%. Our results are comparable to most international series of high volume of transplants, with lower rates of retransplantation.15,16
REFERENCES 1. National Institutes of Health Consensus Development Conference Statement: liver transplantationdJune 20-23, 1983. Hepatology. 1984;4(1 Suppl):107Se110S. 2. Polak WG, Peeters PM, Slooff MJ. The evolution of surgical techniques in clinical liver transplantation. A review. Clin Transplant. 2009;23(4):546e564. 3. Williams R. Forty years of liver transplantation in the United Kingdomdreflections on challenges and achievements. Transplantation. 2009;87(9):1268e1272. 4. Otte JB, et al. Sequential treatment of biliary atresia with Kasai portoenterostomy and liver transplantation: a review. Hepatology. 1994;20(1 Pt 2):41Se48S. 5. Iglesias J, et al. Liver transplantation in infants weighing under 7 kilograms: management and outcome of PICU. Pediatr Transplant. 2004;8(3):228e232. 6. Arnon R, et al. Liver transplantation in children weighing 5 kg or less: analysis of the UNOS database. Pediatr Transplant. 15(6): 650e658. 7. Kaur S, et al. Outcome of live donor liver transplantation in Indian children with bodyweight
