209 Liver transplantation in children with biliary atresia (BA) and no prior hepatoportoenterostomy (NHPE)

HEPATOLOGY, Vol. 38, No. 4, Suppl. 1, 2003

AASLD ABSTRACTS

2O9 LIVER TRANSPLANTATION IN CHILDREN WITH BILIARY A T R E S I A (BA) A N D N O P R I O R

HEPATOPORTOENTEROSTOMY (NHPE). Benjamin L Shneider,

Sukru~ mre, Mount Sinai School of Medicine, New York, NY; Ravinder Anand, The~ MM~ S Corporation, Rockville, MD Introduction: Unrepaired biliary atresia (BA) is an absolute indication to proceed with liver transplantation, since survival beyond two years of age is unlikely. Typically transplantation occurs after complications of liver disease (standard approach - SA). Failure to thrive and development of ascites are often the first complications to develop in children with unrepaired BA. We analyzed the SPLIT database to assess whether transplantation prior to the onset of these complications (preemptive approach - PA) is feasible and/or effective. Methods: Prospective information was collected from a cohort of children who were listed for liver transplantation and followed in the Study for Pediatric Liver Transplantation. The results of transplantation in children with BA who had not undergone prior hepatoportoenterostomy (NHPE) were specifically assessed. Results: 1761 children (693 with BA) were registered in SPLIT. 450 of the 693 BA patients underwent their first liver transplant while on the registry, 67 (14.9%) of w h o m had NHPE. Children with NHPE were more likely to be female (74.6% vs 60.8%, p<.05) or black (31.3% vs 17.0%, p<.05). More than two-thirds of children with NHPE typically developed failure to thrive or ascites by the age of 12 months (age in months: Kaplan-Meier probability of failure to thrive or ascites, 3:3, 6:32, 12:69, 15:77, 18:80, 21:83, 24:85). One year survival after liver transplantation was greater in NHPE w h e n transplantation occurred prior to the onset of either FTr or ascites (Kaplan-Meier probability: PA 15/15 [100%] versus SA 44/52 [79%] p - 0.14, [note 7 out of 8 deaths occured in recipients of cadaveric grafts]). Initial hospital stay after liver transplantation was shorter after PA (PA 25.1 -+ 2.6 versus SA 35.0 -+ 8.4 days, p 0.85). There was no difference in biliary tract complications, hepatic artery or portal vein thrombosis in PA compared to SA. Conclusions: A pre-emptive approach to liver transplantation in children with unrepaired BA is feasible and may yield a greater survival rate with lower length of hospitalization. Consideration should be given to prioritization of children with unrepaired BA, since they are unlikely to receive a cadaveric organ before the onset of complications. Future studies will be necessary to determine if these findings can be extrapolated to children with a failed HPE. This study is sponsored by an educational grant from Fujisawa Healthcare, Inc. with additional support from Wyeth-Ayerst Laboratories, Roche Laboratories and MedImmune, Inc. Disclosures: Ravinder A n a n d - No relationships to disclose Sukru Emre - No relationships to disclose Benjamin L Shneider - No relationships to disclose The Studies of Pediatric Liver Transplantation - No relationships to disclose

210 ZOLEDRONIC ACID PREVENTS BONE LOSS AT 3 MONTHS IN LIVER TRANSPLANT PATIENTS: AN INTERIM ANALYSIS. Bronwyn A L Crawford, Royal Pm'nceAlfred Hospital

and the University of Sydney, Sydney, Australia; Cherie Kam, Royal Prince Alfred Hospital, Sydney, Australia; ]ulie Pavlovic, The Austin Repatriation Medical Centre, Melbourne, Australia; Anthony J Donaghy, Royal Prince Alfred Hospital, Sydney, Australia; Peter Angus, The Austin Repatriation Medical Centre, Melbourne, Australia; Geoffrey McCaughan, Royal Pm'nceAlfred Hospital and the University of Sydney, Sydney, Australia Osteoporosis and fracture are frequent complications of liver transplantation. Whilst decreased bone formation may be a factor in metabolic bone disease in cirrhosis, increased bone resorption is the predominant pathogenetic mechanism underlying the acute bone loss associated with transplantation and is related to factors such as immunosuppressive therapy, immobilisation, hypogonadism, malnutrition and vitamin D deficiency. We undertook a randomised, placebocontrolled, double blind study in liver transplant patients of zoledronic

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acid, a bisphosphonate with potent anti-resportive properties. The hypothesis was that zoledronic acid would prevent the loss of bone that occurs after transplantation. As previous studies~ have shown the greatest bone loss occurring at 3 months post-transplant, this was selected as the primary end-point; the secondary endpoints were bone density (BMD) at 6 and 12 months, and biochemical markers of bone turnover. Approval for the study was given by the Insitutional H u a m n Ethics Review Committee and consent for the study was given at the time of transplant work-up. All patients received ergocalciferol 1000 U and calcium carbonate 600 mg daily. Zoledronic acid 4 mg, or placebo (saline) was given in 100 ml N/Saline over 15 rain within 7 days after transplantation (average 2.7 days) and again at 1, 3, 6, and 9 months post-transplantation. Bone mineral density (BMD) of the hip, lumbar spine (LS) and total body was measured by dual xray absorptiometry on a Lunar densitometer at baseline (within 6 months prior to transplantation) and then 3, 6 and 12 months post-transplantation. Patients were stratified by age, sex, baseline BMD and primary immunosuppressive therapy (cyclosporine or tacrolimus). Data is mean (SEM). An interim analysis of the primary end-point (BMD at 3 months post-transplant) was carried out on the first 45 patients (33 male, 12 female) aged 48.6 (1.4) yrs. The 2 treatment groups were well balanced with respect to underlying disease (viral hepatitis in 64%), severity of cirrhosis prior to transplant (average Child Pugh score 9.5) and 25 hydroxyvitamin D levels (40 nmol/L). The average baseline BMD T scores (SD) were: LS -1.1 SD, neck of femur (NOF) -%0 SD, hip -0.6 SD, Ward's -1.6 SD, trochanter -0.9 SD. For all BMD parameters the placebo group lost bone at 3 months, ranging from 2.8% in the LS to 8.0% in the trochanter. This loss was prevented by treatment with zoledronic acid at all sites and was highly significant for all hip parameters (total hip and Ward's p<0.000% NOF p-0.002, trochanter p-0.02; LS p+0.09). We conclude that intravenous administration of zoledronic acid at the time of transplant and one month post-transplant prevents the acute bone loss associated with liver transplantation. 1. McDonald et al Hepatology 1991 14:61309

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Disclosures: Peter Angus - No relationships to disclose Bronwyn A L Crawford - No relationships to disclose Anthony J Donaghy - No relationships to disclose Cherie Kam - No relationships to disclose Geoffrey McCaughan - No relationships to disclose Julie Pavlovic - No relationships to disclose