Internalizing motivation to self-care: a multifaceted challenge for young liver transplant recipients.

The transition from parent-controlled care to self-managed care represents an important challenge for adolescents with chronic conditions. We sought to gain a deeper understanding of the factors influencing the internalization of motivation to self-care in adolescent liver transplant recipients. We conducted a qualitative study using in-depth interviews with 18 young patients. We triangulated the data collected from the patients with data from parents and health care providers, and used an inductive approach to analyze the data. Our results illustrate three interrelated challenges that impact on young patients' motivation to self-care: (a) the cognitive challenge of fully understanding one's condition and personal health risks; (b) the behavioral challenge of developing independence regarding self-management issues; and (c) the psychological challenge of building a sense of self-ownership and purpose. The latter involves overcoming the trauma of survival and coming to terms with feelings of obligation, two challenges inherent to transplantation that warrant further investigation.

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.

Non-adherence in adolescent transplant recipients: the role of uncertainty in health care providers.

To optimize self-management and adherence in adolescent patients, HCPs need to discuss not only medical and treatment-related issues, but also general health and psychosocial concerns. Our study aimed to explore how the members of the paediatric team in our programme understand NA in adolescents, and how they define their own role regarding self-management education. We used a sequential mixed methods design and conducted a qualitative observational and in-depth interview study (n=22) and a quantitative descriptive study through self-administered questionnaires (n=31). Our results show a discrepancy between the HCPs' understanding of the complex psychosocial factors impacting on long-term adherence, and their current limited practice of patient education. A number of uncertainties were found to explain the HCPs' perceived difficulty to engage in comprehensive patient education activities: uncertainty regarding (i) the health status of transplant recipients; (ii) a shared operational definition of adherence and the cause of organ rejection in some cases; (iii) the extent to which adherence is a shared responsibility which involves the HCPs as patient educators; (iv) the long-term impact of a LRD. To avoid the risk of conveying incongruent messages, multidisciplinary health care teams need to explicitly acknowledge and discuss the various areas of uncertainty, some of which are inherent to transplantation.

Steroid withdrawal after pediatric liver transplantation: a long-term follow-up study in 109 recipients.

BACKGROUND: Steroids remain an important component of maintenance immunosuppression in liver transplantation, but when administered for a long period they may be associated with multiple severe side effects, particularly growth suppression in children. This study was conducted to clarify the balance of potential benefits and risks of steroid withdrawal (SW) in pediatric liver transplantation. METHODS: Between April 1984 and July 2000, 109 pediatric recipients with SW and at least 12 months of follow-up after SW were retrospectively reviewed and divided into three groups according to the type of anticalcineurin at SW: group I (cyclosporine, n=25), group II (cyclosporine microemulsion, n=25), and group III (tacrolimus, n=59). Steroids were withdrawn after a three-step reduction of steroid dosage (taper down to the substitution dose of 0.25 mg/kg/day, switch to alternate-day therapy, progressive SW). Patients were regularly followed up for clinical and biochemical monitoring. RESULTS: Median follow-up was 8.1 (range, 1.6-16.8) years. After SW, neither chronic rejection nor graft nor patient loss occurred. A trend toward lower anticalcineurin trough levels was observed in all groups. Glomerular filtration rate and fasting cholesterol were significantly better in group III (P<0.05). Median height z-score in all patients was -1.1 SD on alternate-day steroids versus -0.2 SD at the time of SW. Height z-score was slightly better in group III (NS). Early SW within 2 years after transplantation allowed a slightly better gain in growth. CONCLUSIONS: SW in pediatric liver transplantation is safe and may be beneficial to height outcome. Tacrolimus seems to offer several advantages in the long-term outcome.

Quality control of the European Liver Transplant Registry: results of audit visits to the contributing centers.

BACKGROUND: The number of registries is increasing, but few of them perform reliability audits by comparing the data contained in the database with data contained in hospital charts. METHODS: The European Liver Transplant Registry (ELTR) cocoordinating committee appointed an independent team to check the reliability of data contained in ELTR. Centers were selected at random. Ten percent of each center's files were selected at random, and 25 items per file were checked during the site visits. The rates of completeness and inconsistencies and the agreement between ELTR and charts were established. We also assessed the correlation between the quality of data and the visited centers' activity. RESULTS: Seven hundred thirty-four files from 21 centers have been audited between June 1998 and June 2001. The rate of ELTR completeness was 95%, and the rate of consistency between charts and ELTR was 98%. The agreement between the ELTR and charts review was very good for all conditions (kappa value < or =0.81). However, comparisons of rates between items indicated that specific items, mostly cause of death or graft failure and patient outcome, should be targeted for improvement. No significant correlation was found between the quality of data and the experience of visited centers. The mean (min-max) and median cost per audited file were EUR 60 (8-150) and EUR 44, respectively. CONCLUSION: The results of audit visits indicate that ELTR data are reliable, and the scientific results of ELTR can be considered credible and representative of liver transplantation in Europe. The method could serve as a model for auditing a registry.

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.

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, n = 58; late reLT, n = 32), according to the interval between either transplant procedures (< or >30 days). Ten-year patient survival rate was 85% in recipients with a single LT, vs. 61% in recipients requiring reLT (P < 0.001). Ten-year patient survival rates were 59% and 66% for early and late reLT, respectively (P = 0.423), the corresponding graft survival rates being 51% and 63% (P = 0.231). 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.

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

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, gamma-glutamyl transpeptidase and bilirubin levels after transplantation in both donor and recipient series. Thirteen recipients and 14 donors are alive and well 3-10 yr post-surgery. One PFIC recipient died nine months 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.

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

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.

Liver allograft radiotherapy to treat rejection in children: efficacy in orthotopic liver transplantation and long-term safety.

BACKGROUND: We studied, retrospectively, the efficacy to control rejection and long-term safety of liver allograft radiotherapy (RT) performed in 14 children. Long-term safety data were collected with the prospect of possible use of RT in liver cell transplantation (LCT). METHODS: Immune suppression included cyclosporine, azathioprine and prednisone. In case of intractable rejection, low-dose allograft RT was administered daily for 3 days, and short-term efficacy was evaluated by liver enzyme assays and histology. The long-term outcome was compared with that of 122 patients undergone transplantation and who had similar treatment, but no RT. RESULTS: Survival at 15 years was 71.4% vs 69.7% in the comparison group. In the RT group, rejection control was complete in six of 14 children and partial in two, all being alive and well 14-18 years later. Ten of 14 children had follow-up biopsy. Six children had normal histology and four had mild unspecific fibrosis. The long-term follow-up biopsy in the comparison group showed fibrosis in 42 of 85 children. The incidence of complications was similar in both groups. CONCLUSIONS: This series shows that, such a RT regimen appeared to be efficient and safe as a rescue treatment for acute rejection. Provided that further investigations in animal models show a certain benefit of low-dose irradiation around LCT, such a regimen could be proposed in human liver cell transplant programmes.

Stepwise minimization of the immunosuppressive therapy in pediatric liver transplantation. A conceptual approach towards operational tolerance.

The evolution of immunosuppression in pediatric liver transplantation has been characterized by a steady reduction of the immunosuppressive load, including removal of anti-lymphocyte antibodies, with the aim to reduce the incidence of EBV-related post-transplant lymphoproliferative disorders. Acute rejection rates were studied retrospectively over two decades of pediatric liver transplantation, according to the successive immunoprophylactic regimens. 318 primary pediatric liver transplant recipients, included between 1984 and 2004 in successive prospective trials, were analyzed, with respect to the impact of the immunosuppressive protocol on acute rejection occurrence. A progressive decrease of rejection incidences was observed, which corresponded to reduced immunosuppressive load and to transplant eras. Such trend might be related to changing approaches towards acute rejection histology and therapy by transplant clinicians, but also to the stepwise minimization of immunosuppressive protocols, putatively enhancing graft acceptance. We hypothesize that the recent population of liver transplant recipients with low immunosuppression might be more suitable for progressive immunosuppression withdrawal trial, with the aim to reach ultimately operational tolerance.

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

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.

Long-term survival and late graft loss in pediatric liver transplant recipients--a 15-year single-center experience.

Increasing numbers of children undergo successful liver transplantation. Limited data exist on long-term survival and late graft loss. Survival and graft loss were studied in 376 primary liver graft recipients who survived more than 3 months after transplantation (80.5% of all primary graft recipients). Patient records were reviewed retrospectively for causes of graft loss. Risk factors were identified by analyzing graft, recipient, and posttransplant variables using multivariate Cox regression. One-, 5-, and 10-year actuarial graft survival rates in the study population were 94.6%, 87.3%, and 86.3%, respectively. Corresponding patient survival rates were 95.7%, 91.4%, and 90.4%. Forty-seven (12.5%) grafts were lost subsequently, 15 by patient death with preserved graft function. Survival rate after late retransplantation was 63.3%. Causes of late graft loss were infection (21.2%), posttransplant lymphoproliferative disease (PTLD, 21.2%), chronic rejection (17%), biliary complications (14.8%), and recurrence of malignant disease (8.5%). Independent risk factors for late graft loss and patient death included liver malignancy as primary disease, steroid resistant rejection, and PTLD. Graft loss rate was significantly increased for reduced-size grafts. Patients undergoing transplantation after 1991 and recipients of full-size grafts were more likely to survive. In conclusion, the long-term outcome for pediatric primary liver graft recipients surviving the early postoperative period is excellent except for patients with liver malignancy. There is no increased risk of late graft loss with the use of split or living related donor grafts. Technical complications are only a minor factor in late graft loss, but complications related to immunosuppression and infection remain a major hazard and must be addressed.