Magdalena Janssen

Steroid-free, tacrolimus-basiliximab immunosuppression in pediatric liver transplantation: Clinical and pharmacoeconomic study in 50 children†

Corticosteroid‐free immunosuppression (IS) may be potentially beneficial for transplanted patients, particularly children. The purpose of this study was to evaluate the efficacy and cost of such strategy in primary pediatric liver transplantation (LT). Fifty pediatric LT recipients were prospectively treated with a steroid‐free, tacrolimus‐basiliximab–based IS (group TB). A group of 34 children transplanted under a conventional tacrolimus‐steroids regimen served as control series (group TS). Groups TB and TS were compared regarding patient and graft survival, rejection incidence, infectious complications, and growth, as well as cost of the transplant procedure. Patient and graft survivals at 3 years were 96% and 94% in group TB, versus 91% and 88% in group TS (P = 0.380 and P = 0.370, respectively). Rejection‐free graft survival at 3 years was 72% in group TB, versus 41% in group TS (P = 0.007). Patients in group TB had significantly less viral infections than patients in group TS (P = 0.045). Height standard deviation score was significantly enhanced in children from group TB, when compared to group TS. Medical care costs were similar in both groups. Steroid avoidance together with basiliximab immunoprophylaxis was not harmful in terms of allograft acceptance, and even seemed to be beneficial in the long term. Liver Transpl, 2008.

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 fiveu2003yr 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.

Living-related liver transplantation and vena cava reconstruction after total hepatectomy including the vena cava for hepatoblastoma.

Background. In most cases of total hepatectomy (TH) required for hepatoblastoma (HB), the retrohepatic inferior vena cava (IVC) has to be removed with the native liver for complete tumor excision. Because the liver graft procured by living donation has no IVC, a reconstruction of the recipient IVC is needed. We report our experience with living‐related liver transplantation (LRLT) and IVC replacement in such cases. Methods. Between May 1998 and December 1999, four children underwent TH, including IVC and LRLT with IVC replacement for otherwise irresectable HB after chemotherapy (SIOPEL 2 and 3 protocols). IVC reconstruction used an allogenic iliac vein procured from a cadaveric donor (bank graft) in two cases and an internal jugular vein procured from the donor parent in two cases. Median age and weight at surgery were 17 months (range 10‐60) and 9.6 kg (range 8.3‐17.9). Results. In the living donors, there were two complications of the procurement: one intra‐abdominal biliary collection and one subcutaneous abscess. In all four children, complete excision of the tumor could be achieved without any intra‐operative complication. One patient died 5 months after LRLT due to lung metastases. Three patients were alive and well with no evidence of tumor recurrence 13‐24 months after surgery. Reconstructed IVC was patent in two patients, and asymptomatic thrombosis occurred 2 years after operation in one patient. Conclusion. Total hepatectomy including the retrohepatic IVC is not a technical obstacle to LRLT. Therefore, scheduled surgery, at the best time after chemotherapy, can be considered in all patients with otherwise irresectable HBs.

Non‐adherence in adolescent transplant recipients: The role of uncertainty in health care providers

Aujoulat I, Deccache A, Charles A‐S, Janssen M, Struyf C, Pélicand J, Ciccarelli O, Dobbels F, Reding R. Non‐adherence in adolescent transplant recipients: The role of uncertainty in health care providers.u2028Pediatr Transplantation 2011: 15:148–156.

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.

Safety of living-related liver transplantation for progressive familial intrahepatic cholestasis.

Abstract:u2002 Progressive familial intrahepatic cholestasis (PFIC) is a severe cholestatic liver disease of early life often requiring liver transplantation. Organ shortage leads to consider living‐related liver transplantation. Because of possible partial metabolic defect in heterozygotes, the use of familial donors might be questionable. We therefore evaluated the safety of this procedure, for both donors and recipients. We compared a series of seven parental–children pairs, having participated in the living related liver transplant program for PFIC between 1994 and 2001, with that of a series of seven parental–children pairs, performed for biliary atresia (BA) during the same period. No primary graft dysfunction was observed. There was no difference in the course of transaminases, γ‐glutamyl transpeptidase and bilirubin levels after transplantation in both donor and recipient series. Thirteen recipients and 14 donors are alive and well 3–10u2003yr post‐surgery. One PFIC recipient died nineu2003months post‐orthotopic liver transplantation from sepsis. We conclude that PFIC heterozygote status of the donor does not increase the risk of liver dysfunction in either recipients or donors, with a similar course compared with BA recipients and donors.

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% (nu2009=u200998). 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 (Pu2009<u20090.001 and Pu2009=u20090.003, respectively). Anastomotic BCs were managed primarily with surgical repair in 59 of 60 cases with a primary patency rate of 80% (nu2009=u200947). 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.

Living Donor Liver Transplantation in Children: Surgical and Immunological Results in 250 Recipients at Université Catholique de Louvain.

Objectives: To evaluate the outcome of pediatric living donor liver transplantation (LDLT) regarding portal vein (PV) reconstruction, ABO compatibility, and impact of maternal donation on graft acceptance. Background: LDLT and ABO-mismatched transplantation constitute feasible options to alleviate organ shortage in children. Vascular complications of portal hypoplasia in biliary atresia (BA) and acute rejection (AR) are still major concerns in this field. Methods: Data from 250 pediatric LDLT recipients, performed at Cliniques Universitaires Saint-Luc between July 1993 and June 2012, were collected retrospectively. Results were analyzed according to ABO matching and PV complications. Uni- and multivariate analyses were performed to study the impact of immunosuppression, sex matching, and maternal donation on AR rate. Results: Overall, the 10-year patient survival rate was 93.2%. Neither patient or graft loss nor vascular rejection, nor hemolysis, was encountered in the ABO nonidentical patients (nu200a=u200a58), provided pretransplant levels of relevant isoagglutinins were below 1/16. In BA recipients, the rate of PV complications was lower after portoplasty (4.6%) than after truncal PV anastomosis (9.8%) and to jump graft interposition (26.9%; Pu200a=u200a0.027). In parental donation, maternal grafts were associated with higher 1-year AR-free survival (55.2%) than paternal grafts (39.8%; Pu200a=u200a0.041), but only in BA patients. Conclusions: LDLT, including ABO-mismatched transplantation, constitutes a safe and efficient therapy for liver failure in children. In BA patients with PV hypoplasia, portoplasty seems to constitute the best technique for PV reconstruction. Maternal donation might be a protective factor for AR.

Liver retransplantation in children. A 21-year single-center experience*

In this study, the epidemiology and outcome of graft loss following primary pediatric liver transplantation (LT) were analysed, with the hypothesis that early retransplantation (reLT) might be associated with lower immunologic risks when compared with late reLT. Between March 1984 and December 2005, 745 liver grafts were transplanted to 638 children at Saint‐Luc University Hospital, Brussels. Among them, a total of 90 children (14%) underwent 107 reLT, and were categorized into two groups (early reLT, nu2003=u200358; late reLT, nu2003=u200332), according to the interval between either transplant procedures (< or >30u2003days). Ten‐year patient survival rate was 85% in recipients with a single LT, vs. 61% in recipients requiring reLT (Pu2003<u20030.001). Ten‐year patient survival rates were 59% and 66% for early and late reLT, respectively (Pu2003=u20030.423), the corresponding graft survival rates being 51% and 63% (Pu2003=u20030.231). Along the successive eras, the rate of reLT decreased from 17% to 10%, whereas progressive improvement of outcome post‐reLT was observed. No recurrence of chronic rejection (CR) was observed after reLT for CR (0 of 19). Two children developed a positive cross‐match at reLT (two of 10, 20%), both retransplanted lately for CR secondary to immunosuppression withdrawal following a post‐transplant lymphoproliferative disease. In summary, the results presented could not evidence better results for late reLT when compared with early reLT. The former did not seem to be associated with higher immunologic risk, except for children having withdrawal of immunosuppression following the first graft.

Efficacy and pharmacokinetics of tacrolimus oral suspension in pediatric liver transplant recipients.

Abstract: The use of tacrolimus in small pediatric graft recipients may require the availability of a suspension formulation for appropriate dose titration and easier administration. The pharmacokinetics (Pk) of an extemporaneously prepared oral suspension of tacrolimus (OST) was investigated in 15 pediatric liver transplant recipients, and was compared with the corresponding data with tacrolimus capsules (TC). Graft and patient survival rates were 100%. Acute rejection and steroid‐resistant rejection were encountered in 9/15 and 3/15 patients, respectively. Comparison of Pk data showed a lower oral absorption of OST when compared with TC. No significant correlation could be made between the Pk parameters and rejection. Despite the lower bioavailability of OST when compared with TC, the rejection incidence was similar with both formulations (60% vs. 55%, respectively). Accordingly, the use of OST may constitute an alternative option for tacrolimus administration in low body weight organ recipients, to allow dosage titration in the early post‐transplant weeks.