Christophe Bourdeaux

Living‐Related Versus Deceased Donor Pediatric Liver Transplantation: A Multivariate Analysis of Technical and Immunological Complications in 235 Recipients

Timely access to a living donor (LD) reduced pretransplant mortality in pediatric liver transplantation (LT). We hypothesized that this strategy may provide better posttransplant outcome. Between July 1993 and April 2002, 235 children received a primary LT from a LD (n = 100) or a deceased donor (DD) (n = 135). Demographic, surgical and immunological variables were compared, and respective impact on posttransplant complications was studied using a multivariate analysis. Five‐year patient survival rates were 92% and 85% for groups LD and DD, respectively (p = 0.181), the corresponding graft survival rates being 89% and 77% (p = 0.033). At multivariate analysis: (1) type of donor (DD) was correlated with higher rate of artery thrombosis (p < 0.012); (2) biliary complication rate at 5 years was 29% and 23% for groups LD and DD, respectively (p = 0.451); (3) lower acute rejection incidence could be correlated with type of donor (DD) (p = 0.001), and immunosuppressive therapy (tacrolimus) (p < 0.001). We conclude that (1) according to the multivariate analysis, LT with LD provided similar patient and graft outcome, when compared to DD; (2) a higher rate of artery thrombosis and a lower rate of rejection were observed in group DD; (3) this study comfirms the efficacy of tacrolimus for immunoprophylaxis, whatever the type of organ donor is.

Pediatric liver transplantation using left hepatic segments from living related donors: Surgical experience in 100 recipients at Saint-Luc University Clinics

Abstract: Living‐related liver transplantation was developed in the context of deceased donor organ shortage, which is particularly acute for pediatric recipients. This retrospective study analyzes the surgical technique and complications in the first 100 pediatric liver transplantation using left segmental liver grafts from living donors, performed at Saint‐Luc University Clinics between July 1993 and April 2002. Pre‐operative evaluation in donors and recipients, analysis of the surgical technique, and postoperative complications were reviewed. After a median follow‐up period of 2526 days, no donor mortality was encountered, with a minimal morbidity and no long‐term sequelae. At one and five yr post‐transplantation, the actuarial patient survival rates were 94% and 92%, the corresponding figures being 92% and 89% for graft survival. The incidences of portal vein and hepatic artery thromboses, and of biliary complications were 14%, 1%, and 27%, respectively. Living‐related liver transplantation in children constitutes an efficient therapy for liver failure to face the increased demand for liver grafts. Donor morbidity was kept to acceptable incidence, and surgical technique in the recipient needs to be tailored to minimize postoperative complications.

PELD score and posttransplant outcome in pediatric liver transplantation: a retrospective study of 100 recipients.

Background. Pediatric End-stage Liver Disease (PELD) score is proposed as an objective tool to prioritize children awaiting liver transplantation (LT), higher PELD being associated with increased pre-LT mortality. This study investigated whether PELD may also impact on post-LT results. Methods. PELD was retrospectively analyzed in 100 pediatric recipients of a primary LT from living-related (n = 49) or postmortem donors (PMD, n = 51). The main pre-LT diagnosis was biliary atresia (n = 64), hepatic malignancy and fulminant hepatitis cases being excluded. PELD was calculated in all patients at the time of pre-LT assessment. Considering the median delay of 117 days between listing and LT in the PMD subgroup, a second PELD was calculated at the time of LT, allowing the determination of a &Dgr;PELD during the waiting period. PMD grafts were allocated using an allocation system taking into account waiting times as well as medical urgency, operative at EuroTransplant. Results. Overall 5-year actuarial patient and graft survivals were 96% and 91%, respectively. PELD at listing (13.3 ± 9.7) showed a normal statistical distribution. PELD scores at listing and at LT were not found to significantly impact on post-LT outcome (NS). In contrast, higher &Dgr;PELD might be associated with lower posttransplant patient survival (p = 0.094). Conclusions. The results of this retrospective analysis suggest that giving priority to high PELD recipients may not result in worsening post-LT outcome. Accordingly, these data support such “sickest children first” allocation policy, which should contribute to reduce pre-LT mortality without worsening post-LT results and increasing organ waste.

Impact of pre-transplant liver hemodynamics and portal reconstruction techniques on post-transplant portal vein complications in pediatric liver transplantation : a retrospective analysis in 197 recipients

Background and Objective:Portal vein (PV) complications are the most frequent vascular complications in pediatric liver transplant (LT). We hypothesized that pre-LT liver hemodynamic parameters and PV reconstruction technique could predict the risk of PV complications post-LT. Methods:Three hundred seventy-three children had a primary LT. A detailed ultrasound study of the pre-LT native liver hemodynamics was available in 198 cases, with details of PV anastomosis available for 197 of these: end-to-end anastomosis (n = 146, 74%), interposition vein graft technique (n = 28, 14%), or portoplasty (latero-lateral anastomosis of vein graft and recipient PV) (n = 23, 12%). Results:Overall 5-year patient survival rate was 90%. Among the 198 patients with pre-LT hemodynamic data, 79 (40%) had PV hypoplasia (diameter ⩽4 mm), 64 (32%) had a pathological portal flow (nonhepatopetal flow), and 47 (24%) had an arterial resistance index (ARI) ≥1. Abnormal hemodynamics were mostly observed in biliary atresia (BA). Among these 3 parameters, only ARI ≥1 was significantly correlated with a higher rate of PV complications post-LT (P = 0.041). PV complication-free survival at 5 years were 91% for end-to-end anastomosis, 91% for portoplasty, and 62% for interposition vein graft technique (P = 0.002). At multivariate analysis, the use of an interposition vein graft was the only factor to be significantly associated with a higher rate of PV complications post-LT (P = 0.003). Conclusions:PV hypoplasia with liver hemodynamic disturbances was mainly observed in BA. Hepatic ARI ≥1 might be a good predictor of PV complications post-LT. Latero-lateral portoplasty seemed to provide the best results when end-to-end anastomosis is not feasible.

Risk factors and surgical management of anastomotic biliary complications after pediatric liver transplantation.

Biliary complications (BCs) still remain the Achilles heel of liver transplantation (LT) with an overall incidence of 10% to 35% in pediatric series. We hypothesized that (1) the use of alternative techniques (reduced size, split, and living donor grafts) in pediatric LT may contribute to an increased incidence of BCs, and (2) surgery as a first treatment option for anastomotic BCs could allow a definitive cure for the majority of these patients. Four hundred twenty‐nine primary pediatric LT procedures, including 88, 91, 47, and 203 whole, reduced size, split, and living donor grafts, respectively, that were performed between July 1993 and November 2010 were retrospectively reviewed. Demographic and surgical variables were analyzed, and their respective impact on BCs was studied with univariate and multivariate analyses. The modalities of BC management were also reviewed. The 1‐ and 5‐year patient survival rates were 94% and 90%, 89% and 85%, 94% and 89%, and 98% and 94% for whole, reduced size, split, and living donor liver grafts, respectively. The overall incidence of BCs was 23% (n = 98). Sixty were anastomotic complications [47 strictures (78%) and 13 fistulas (22%)]. The graft type was not found to be an independent risk factor for the development of BCs. According to a multivariate analysis, only hepatic artery thrombosis and acute rejection increased the risk of anastomotic BCs (P < 0.001 and P = 0.003, respectively). Anastomotic BCs were managed primarily with surgical repair in 59 of 60 cases with a primary patency rate of 80% (n = 47). These results suggest that (1) most of the BCs were anastomotic complications not influenced by the type of graft, and (2) the surgical management of anastomotic BCs may constitute the first and best therapeutic option. Liver Transpl 20:893‐903, 2014.

The immunological monitoring of kidney and liver transplants in adult and pediatric recipients

Over the last half century, kidney and liver transplantation have been recognized as the treatment of choice for adult and children with end-stage renal or liver failure. Infants present a relative naïve immune system, but they are capable of mounting both cellular and humoral immune responses to the foreign antigens presented by the allograft. Immune monitoring is a way of measuring functional and molecular correlates of immune reactivity which may provide clinically useful information for identifying patients who have an increase risk of acute rejection prior to clinical symptoms or develop transplant tolerance. However, although numerous assays have been shown to predict rejection, to date no assays have been demonstrated to detect or predict transplantation tolerance. This is a summary of the published literature on promising antigen-specific and non-antigen-specific assays used for immunological monitoring in solid organ transplantation. This work also attempts to review their applicability to pediatric transplantation, specifically, pediatric kidney and liver recipients.

Prope tolerance after pediatric liver transplantation.

pT, under mono‐ and infratherapeutic calcineurin inhibition, may constitute an optimal condition combining graft acceptance with low IS load and minimal IS‐related toxicity. We reviewed 171 pediatric (<15.0 yr) survivors beyond one yr after LT, transplanted between April 1999 and June 2007 under tacrolimus‐based regimens (median follow‐up post‐LT: 6.0 yr, range: 0.8–9.5 yr). Their current status regarding IS therapy was analyzed and correlated with initial immunoprophylaxis. pT was defined as tacrolimus monotherapy, with mean trough blood levels <4 ng/mL during the preceding year of follow‐up, combined with normal liver function tests. The 66 children transplanted before April 2001 received a standard tacrolimus–steroid regimen. Beyond April 2001, 105 patients received steroid‐free tacrolimus–basiliximab or tacrolimus–daclizumab immunoprophylaxis. In the latter group, 43 (41%) never experienced any acute rejection episode and never received steroids. In the long term, a total of 79 recipients (47%) developed pT (n = 73) or IS‐free operational tolerance (n = 6), 27 of them belonging to the 43 steroid‐free patients (63%). In contrast, only 52/128 (41%) children treated with steroids subsequently developed prope/operational tolerance (p = 0.012). Steroid‐free tacrolimus‐based IS seems to promote long‐term graft acceptance under minimal/no IS. These results constitute the first evidence that minimization of IS, including steroid avoidance, might be tolerogenic in the long term after pediatric LT.