Experience with living related liver transplantation in 63 children

The incentive to develop intrafamilial living related liver transplantation (LRLT) originated from the shortage of cadaveric organ supply. We report our experience with LRLT in 63 children during 1993-1998 in the frame of a protocol approved by the Ethics Committee of our Institution. During this period, 152 potential intrafamilial (mostly parental) donors were evaluated; 44 (28,5%) were excluded because of surgical (n = 4), medical (n = 39) or psychosocial reason (n = 1). Out of 108 who matched all medical, surgical and psychological criteria of selection, 45 did not underwent living donation because their child received a cadaveric graft (n = 22; LRLT was their second option) or because one of the parents who had both been selected was chosen [by the surgical team because of more favourable anatomy (n = 8) or by mutual agreement between the two parents (n = 5)]. Sixty-three living donors (36 mothers, 24 fathers, one grand mother, one aunt and one uncle) underwent procurement of the left lobe (n = 52), the left lobe extended to part of segment IV (n = 8) or a left hepatectomy (n = 3) without mortality or any serious morbidity. Their median hospital stay was 7 days (range: 6-12); full physical rehabilitation and normalization of liver tests were usually obtained within three weeks. Their psychological follow-up did not disclose any longstanding serious sequellae. The median age of the recipients was 13 months (range 5-189); 30 were younger than one year at the time of transplant. Their median weight was 8,1 kg (range: 4,3 to 60); 36 had an actual weight under 10 kg. Fifty-two received an ABO identical and 11 received an ABO compatible transplant. The native liver diseases were similar to common data in children, with biliary atresia being the most frequent indication (74,6%). The median weight of the graft was 260 gr (range: 138- 680) with a median ratio between the graft weight and the recipient body weight of 3,17% (range: 0,75-8,08). All grafts were implanted orthotopically with semi-microvascular reconstruction of the hepatic vein, portal vein and hepatic artery [end to end anastomosis in 58 (2 arteries were reconstructed in 7 patients) and interposition of an iliac arterial allograft from the intrarenal aorta in 5]. Base line immunosuppression consisted of a triple drug regimen including steroids, Azathioprine and either Cyclosporine- Sandimmun® (n = 9), Cyclosporine Microemulsion formulation - Neoral® (n = 13) or Tacrolimus- Prograft® (n = 41). Biopsy-proved acute rejection was treated with intravenous bolus of steroids; steroid-resistant acute rejection was treated by a switch from Cyclosporine to Tacrolimus or addition of Mycophenolate-Mofetil (Cellcept®) in Tacrolimus treated patients. Actuarial patient survival was 91,8% and 89,6% after LRLT at one and five years post- transplant, respectively, and 87,5% and 82,8% at one and five years, respectively, in 90 patients who received a cadaveric graft during the same interval. Actuarial graft survival was 91,8% and 84,1% after LRLT at one and five years, respectively, and 76,4% and 73,3% at one and five years, respectively, after cadaveric transplants. Vascular thrombosis was observed in 9,5% of the patients (arterial thrombosis: 1,6%; portal thrombosis: 7,9%) without graft loss. Biliary complications were observed in 26,9% (bile leak from cut surface in 3,1%, anastomotic stricture in 22,2% and intrahepatic stricture in 1,5%); two patients died from septic shock possibly related to uncompletely relieved anastomotic stricture; all other biliary complications were successfully treated either conservatively or surgically. The incidence of acute rejection was 90,9% in 22 patients with Cyclosporine-based immunosuppression; acute rejection was cortico-resistant in 50%. It was 46,3% in 41 patients with Tacrolimus-based immunosuppression (64% with Prograft® in capsules and 18,7% with Prograft® in granules); no acute rejection was cortico-resistant. One patient in each group developed chronic rejection (in spite of switch to Tacrolimus in a patient initially treated with Cyclosporine and following full withdrawal of immunosuppression for posttransplant lymphoproliferation in a patient immunosuppressed with Tacrolimus); both patients were successfully retransplanted with a cadaveric graft. The incidence of posttransplant lymphoproliferative disorder was 14,2% and similar whatever the main immunosuppressant (13,6% in the Cyclosporine group and 14,6% in the Tacrolimus group). One of the 9 patients with PTLD died of uncontrolled disease. In conclusion, clear ethical guidelines in the frame of a protocol approved by the Institution Ethics Committee should be followed in living related liver transplantation. Safety for the donor should be maximized; extensive surgical expertise with all types of liver resection and transplants including split grafts is a prerequisite. Results regarding patient and graft survival are superior to those obtained with cadaveric transplants. Implementation of LRLT in expert teams is a valid way to obviate the shortage of cadaveric transplants.