Studies Of Pediatric Liver Transplantation Research Articles

Cognitive Function Post Liver Transplant

Research Article| October 01 2014 Cognitive Function Post Liver Transplant AAP Grand Rounds (2014) 32 (4): 45. https://doi.org/10.1542/gr.32-4-45 Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Facebook Twitter LinkedIn MailTo Tools Icon Tools Get Permissions Cite Icon Cite Search Site Citation Cognitive Function Post Liver Transplant. AAP Grand Rounds October 2014; 32 (4): 45. https://doi.org/10.1542/gr.32-4-45 Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search toolbar search search input Search input auto suggest filter your search All PublicationsAll JournalsAAP Grand RoundsPediatricsHospital PediatricsPediatrics In ReviewNeoReviewsAAP NewsAll AAP Sites Search Advanced Search Topics: cognitive ability, liver transplantation Source: Sorenson LG, Neighbors K, Martz K, et al. Longitudinal study of cognitive and academic outcomes after pediatric liver transplantation. J Pediatr. 2014; 165(1): 65– 72.e2; doi: https://doi.org/10.1016/j.jpeds.2014.03.032Google Scholar Investigators from the Functional Outcomes Group (FOG), which includes 20 pediatric liver transplant centers in the Studies of Pediatric Liver Transplantation (SPLIT) collaborative, sought to determine the evolution of cognitive and academic deficits in children after liver transplant. Study children were identified and recruited through the SPLIT registry, and were 5–6 years of age when enrolled and ≥2 years posttransplant. Cognitive performance was measured at enrollment (Time 1) and repeated when participants were 7–9 years old (Time 2). Patients were tested with the Wechsler Preschool and Primary Scale of Intelligence (WPPSI), 3rd edition, at Time 1 and the Wechsler Intelligence Scales for Children (WISC), 4th edition, at Time 2. Composite scores were generated for each including Full Scale IQ (FSIQ), Verbal IQ/Verbal Comprehension (VC), Performance IQ/Perceptual Reasoning (PR), and Processing Speed (PS); a Working Memory (WM) composite score was also generated for the WISC-IV. These scores have a mean of 100 and SD of 15 in the normal population. At both time points, the participants also completed the Wide Range Achievement Test, 4th edition, Word Reading and Math Computation subtests and parents and teachers completed the Behavior Rating Inventory of Executive Function (BRIEF). Medical and demographic variables were also collected to determine which predicted cognitive performance. One hundred forty-four patients were tested at Time 1, and 93 (65%) at Time 2. At Time 2, more patients had below-average FSIQ, VC, WM, and Math Computation compared to these scores’ normal distribution. For FSIQ specifically, 29% had scores of 71–85, and 7% had scores ≤70, both of which were significantly different than a normative population (P = .0001). BRIEF scores were also significantly lower than a normative population, but no different than at Time 1. A total of 42% of participants received special education. Identified risk factors for lower FSIQ included one-person household (P < .002), parental education level of some high school or less (P < .01), weight z-score <-2 standard deviations at liver transplantation (P < .03), and intraoperative transfusion requirement (P < .0001). The investigators conclude that, although the majority of children who are post-liver transplant demonstrate average functioning, many have long-term cognitive and academic problems. They report that cognitive outcomes may be predicted by pretransplant and peritransplant variables. Drs Kasper and Neimark have disclosed no financial relationship relevant to this commentary. This commentary does not contain a discussion of an unapproved/investigative use of a commercial product/device. Children with chronic disease often have cognitive impairments.1,2 Deficits in neurocognitive ability translate into reduced academic achievement, difficult social interactions, and lower quality of life. Identification of risk factors for poor outcomes will help direct limited fiscal resources. There is little scientific literature, however, to delineate long-term consequences of disease... You do not currently have access to this content.

Longitudinal Study of Cognitive and Academic Outcomes after Pediatric Liver Transplantation

To determine the evolution of cognitive and academic deficits and risk factors in children after liver transplantation. Patients ≥2 years after liver transplantation were recruited through Studies of Pediatric Liver Transplantation. Participants age 5-6 years at Time 1 completed the Wechsler Preschool and Primary Scale of Intelligence, 3rd edition, Wide Range Achievement Test, 4th edition, and Behavior Rating Inventory of Executive Function (BRIEF). Participants were retested at age 7-9 years, Time 2 (T2), by use of the Wechsler Intelligence Scales for Children, 4th edition, Wide Range Achievement Test, 4th edition, and BRIEF. Medical and demographic variables significant at P ≤ .10 in univariate analysis were fitted to repeated measures modeling predicting Full Scale IQ (FSIQ). Of 144 patients tested at time 1, 93 (65%) completed T2; returning patients did not differ on medical or demographic variables. At T2, more participants than expected had below-average FSIQ, Verbal Comprehension, Working Memory, and Math Computation, as well as increased executive deficits on teacher BRIEF. Processing Speed approached significance. At T2, 29% (14% expected) had FSIQ = 71-85, and 7% (2% expected) had FSIQ ≤70 (P = .0001). A total of 42% received special education. Paired comparisons revealed that, over time, cognitive and math deficits persisted; only reading improved. Modeling identified household status (P < .002), parent education (P < .01), weight z-score at liver transplantation (P < .03), and transfusion volume during liver transplantation (P < .0001) as predictors of FSIQ. More young liver transplantation recipients than expected are at increased risk for lasting cognitive and academic deficits. Pretransplant markers of nutritional status and operative complications predicted intellectual outcome.

Reducing Pediatric Liver Transplant Complications: A Potential Roadmap for Transplant Quality Improvement Initiatives Within North America

Though robust clinical data are available within transplantation, these data are not used for broad-based, multicentered quality improvement initiates. This article describes a targeted quality improvement initiative within the Studies of Pediatric Liver Transplantation (SPLIT) Registry. Using standard statistical techniques and clinical expertise to adjust for data and statistical reliability, we identified the pediatric liver transplant centers in North America with the lowest hepatic artery thrombosis rate and biliary complication rates. A survey was completed to establish current practices within the entire SPLIT group. Surgeons from the highest performing centers presented a detailed, technically oriented overview of their current practices. The presentations and discussion that followed were recorded and form the basis of the best practices described herein. We frame this work as a unique six-step approach roadmap that may serve as an efficient and cost effective model for novel broad-based quality improvement initiatives within transplantation.

Essential Components of Transition to Adult Transplant Services: The Transplant Coordinators' Perspective

Medical and surgical advancements have resulted in improved long-term survival of pediatric liver transplant recipients. As pediatric patients approach school age and adolescence, transplant centers are challenged to facilitate the process of transitioning from pediatric to adult centers. To describe pediatric and adult liver transplant coordinators' perspective regarding practice for transitioning patients to adult-oriented transplant centers. Descriptive Pediatric and adult liver transplant coordinators associated with Studies of Pediatric Liver Transplantation. A total of 35 pediatric liver transplant coordinators and 24 adult liver transplant coordinators completed the survey. Investigator-developed survey to identify current practice for transition process and actual transfer of a patient from pediatric to adult care. Transplant coordinators play an integral role in the transition process, and study results highlight what experienced coordinators believe are important considerations for a successful transition process. Results also highlight the importance of communication and partnership between the pediatric and adult programs.

Pediatric liver transplantation for primary sclerosing cholangitis

Primary sclerosing cholangitis (PSC) is a rare cholestatic liver disease in children. The aim of this study was to determine the characteristics and outcomes of children with PSC who were listed for liver transplantation (LT). Children who underwent transplantation for PSC according to the Studies of Pediatric Liver Transplantation (SPLIT) registry were compared to age-matched children with chronic liver disease who underwent transplantation for other indications. Seventy-nine patients (2.6% of the SPLIT cohort) required LT for PSC. The mean duration of the post-LT follow-up was 36.6 ± 32.7 months. Ulcerative colitis and Crohn's disease were diagnosed before LT in 46.0% and 3.3% of the patients, respectively, and inflammatory bowel disease (IBD) was diagnosed after LT in another 9.8%. The mean age at LT was 12.6 ± 3.9 years, and the mean waiting time was 10.2 ± 12.9 months. The mean z scores for height and weight at LT were significantly lower for the PSC group versus the non-PSC group. For the PSC group, the 1- and 5-year patient survival rates were 98.7% and 86.6%, respectively, and the 1- and 5-year graft survival rates were 93.0% and 76.1%, respectively. Intrahepatic biliary strictures in the first 6 months post-LT and cholangitis in the first 30 days post-LT were more common in the PSC group versus the non-PSC group (3.8% versus 0.8% for intrahepatic biliary strictures, P = 0.03, and 5.1% versus 1.1% for cholangitis, P = 0.01). Recurrent PSC was diagnosed in 9.8% of the patients at a mean of 18.7 ± 13.8 months after LT. IBD was associated with an increased risk of death (log-rank P = 0.01) and recurrent PSC (P = 0.02). Five years post-LT, the mean aspartate aminotransferase level was 60 ± 45 IU/L, and the mean gamma-glutamyltransferase level was 209 ± 302 IU/L; both levels were significantly higher than the levels for non-PSC patients. In conclusion, children with PSC had patient and graft survival rates equaling those of age-matched children who underwent transplantation for other indications. IBD was associated with worse outcomes. Recurrence was observed in 9.8%, and the PSC patients had higher mean liver enzyme levels 5 years post-LT.

A Multivariate Analysis of Pre-, Peri-, and Post-Transplant Factors Affecting Outcome After Pediatric Liver Transplantation

The purpose of this study was to identify significant, independent factors that predicted 6 month patient and graft survival after pediatric liver transplantation. The Studies of Pediatric Liver Transplantation (SPLIT) is a multicenter database established in 1995, of currently more than 4000 US and Canadian children undergoing liver transplantation. Previous published analyses from this data have examined specific factors influencing outcome. This study analyzes a comprehensive range of factors that may influence outcome from the time of listing through the peri- and postoperative period. A total of 42 pre-, peri- and posttransplant variables evaluated in 2982 pediatric recipients of a first liver transplant registered in SPLIT significant at the univariate level were included in multivariate models. In the final model combining all baseline and posttransplant events, posttransplant complications had the highest relative risk of death or graft loss. Reoperation for any cause increased the risk for both patient and graft loss by 11 fold and reoperation exclusive of specific complications by 4 fold. Vascular thromboses, bowel perforation, septicemia, and retransplantation, each independently increased the risk of patient and graft loss by 3 to 4 fold. The only baseline factor with a similarly high relative risk for patient and graft loss was recipient in the intensive care unit (ICU) intubated at transplant. A significant center effect was also found but did not change the impact of the highly significant factors already identified. We conclude that the most significant factors predicting patient and graft loss at 6 months in children listed for transplant are posttransplant surgical complications.

Outcomes in children who underwent transplantation for autoimmune hepatitis

The outcomes of 113 children with autoimmune hepatitis (AIH), registered with Studies of Pediatric Liver Transplantation and who underwent transplantation between 1995 and 2006, were compared with those who underwent transplantation for other diagnoses (non-AIH). A total of 4.9% of liver transplants were for AIH; 81% of these patients had AIH type 1 and most underwent transplantation for complications of chronic disease (60%), the majority in females (72%). Transplantation for fulminant AIH was more common in males (52.5% versus 47.5% chronic; P = 0.042). Patients with AIH differed from non-AIH patients by: age (13.0 ± 0.4 versus 4.6 ± 0.1 years; P < 0.0001), sex (64.6% female versus 52.9%; P = 0.016), ethnicity (48.7% white versus 58.2%; P < 0.0001), initial immunosuppression (tacrolimus-based: 72.6% versus 62.6%; P = 0.045; mycophenolate mofetil use: 31.0% versus 21.6%; P = 0.02), and immunosuppression at 2 years after transplant (monotherapy: 51.9% versus 17.3%; P < 0.0001). Late (>3 months), but not steroid-resistant or chronic, rejection was more common in AIH (log-rank P = 0.0015). The 5-year posttransplant survival for AIH was 86% (95% confidence interval: 73-93). Patient and graft survival, infectious and metabolic complications, and retransplantation rates did not differ between AIH and non-AIH groups. In conclusion, the higher risk for late acute rejection and greater degree of immunosuppression does not compromise outcomes of liver transplantation for AIH. Children who undergo transplantation for AIH in North America are typically female adolescents with complications of chronic AIH type 1 and include more children of African American or Latino American origin compared to the overall liver transplant population. These observations may inform detection, treatment, and surveillance strategies designed to reduce the progression of autoimmune hepatitis and subsequently, the need for transplantation.

School outcomes in children registered in the studies for pediatric liver transplant (SPLIT) consortium

School performance is an important aspect of functional outcomes for pediatric liver transplant (LT) recipients. This longitudinal analysis conducted through the Studies of Pediatric Liver Transplantation (SPLIT) research consortium examines several indicators of school function in these patients. A total of 39 centers participated in data collection using a semistructured questionnaire designed specifically for this study. The survey queried school attendance, performance and educational outcomes including the need for special educational services. Participants included 823 of 1133 (73%) eligible patients, mean age 11.34 +/- 3.84 years, 53% female, median age at LT 4.6 (range 0.05-17.8) years, and mean interval from transplant was 5.42 +/- 2.79. Overall, 34% of patients were receiving special educational services and 20% had repeated a grade, with older participants more likely to have been held back (P = 0.0007). Missing more than 10 days of school per year was reported by one-third of the group, with this level of absence being more common in older participants (P = 0.0024) and children with shorter intervals from LT (P < 0.0001). Multivariate analysis revealed the following factors were associated with the need for special educational services; type of immunosuppression at 6 months post-LT, cyclosporine A (odds ratio [OR] = 1.8, confidence interval [CI] = 1.1-3.1), or other (OR = 4.9, 95% CI = 1.4-17.6) versus tacrolimus, symptomatic cytomegalovirus infection within 6 months of liver transplantation (OR = 3.1, CI = 1.6-6.1), and pretransplant special educational services (OR = 22.5, CI = 8.6-58.4).

Quality-of-life measures for pediatric liver transplant recipients

The study by Alonso et al shows that outcomes of liver transplantation in infants, children, and adolescents can no longer simply be described on the basis of patient and graft survivals. Rather, it is incumbent on pediatric practitioners to ensure that post-transplant complications including: renal dysfunction, hyperlipidemia, hypertension, opportunistic infections, graft rejection, and overall quality-of-life are monitored carefully and interventions appropriately taken in a timely fashion. The present cross-sectional analysis of selected centers, part of the Studies of Pediatric Liver Transplantation (SPLIT) consortium, highlights gaps in emotional and school functioning that need to be addressed in the future so as to be able to enhance the day-to-day functioning and long-term outcomes for these children. The study by Alonso et al shows that outcomes of liver transplantation in infants, children, and adolescents can no longer simply be described on the basis of patient and graft survivals. Rather, it is incumbent on pediatric practitioners to ensure that post-transplant complications including: renal dysfunction, hyperlipidemia, hypertension, opportunistic infections, graft rejection, and overall quality-of-life are monitored carefully and interventions appropriately taken in a timely fashion. The present cross-sectional analysis of selected centers, part of the Studies of Pediatric Liver Transplantation (SPLIT) consortium, highlights gaps in emotional and school functioning that need to be addressed in the future so as to be able to enhance the day-to-day functioning and long-term outcomes for these children.

Linear Growth Patterns in Prepubertal Children Following Liver Transplantation

Factors impacting linear growth following pediatric liver transplantation (LT) are not well understood. This longitudinal analysis examines predictors of linear growth impairment in prepubertal children included in Studies of Pediatric Liver Transplantation. In 1143 children with serial measurements, mean height scores increased from -1.55 at LT to -0.87 and -0.68 at 24 and 36 months post LT with minimal subsequent catch up growth observed until 60 months. Subgroup analysis of height measurements at 24 months (n = 696), 33.8% were below 10th percentile at 24 months post LT. Multivariate analysis revealed linear growth impairment more likely in patients with metabolic disease (OR 4.4, CI: 1.83-10.59) and >18 months of steroids exposure (OR 3.02, CI: 1.39-6.55). Higher percentiles for weight (OR 0.80, CI: 0.65-0.99) and height (OR 0.62, CI: 0.51-0.77) at LT decreased risk. Less linear catch up was observed in patients with metabolic disease, non-Biliary atresia cholestatic diseases and lower weight and higher height percentiles prior to LT. Prolonged steroid exposure and elevated calculated glomerular filtration rate and gamma-Glutamyltransferase following LT were associated with less catch up growth. Linear growth impairment and incomplete linear catch up growth are common following LT and may improve by avoiding advanced growth failure before LT and steroid exposure minimization.

Healy's law and the pediatric liver allograft

Although the long-term care of children who have undergone liver transplantation has a relatively short history, such care has already evolved. This evolution has largely been driven by the availability of new therapies. The biggest current problems are the seemingly conflicting requirements that graft integrity be maintained and that side effects of therapy, most notably renal toxicity, be minimized. Several strategies have shown promise with respect to reducing nephrotoxicity, although long-term data are still awaited. Given the complexity of today's pharmacopoeia, the care of the graft remains a major concern. LFT, liver function test; SPLIT, Studies of Pediatric Liver Transplantation. More fundamental than drug-choice issues, however, as addressed by Ekong et al.1 in this issue of Liver Transplantation, is this question: how should we best monitor the graft? Ekong et al.1 present a summary of their biopsy findings in 63 of 222 long-term (>3 years) liver transplant recipients. Biopsy was prompted in 32 by clinical-laboratory test result [liver function test (LFT)] abnormalities; in this group, unsurprisingly, inflammation and fibrosis were seen. Biopsy to assess liver status in the absence of LFT abnormalities (surveillance biopsy) was offered to 118 longer term (>5 years) survivors, of whom 87 declined. Among the 31 patients who underwent surveillance biopsy at >5 years, 8 had substantial fibrosis, a finding of concern for graft outcome over decades. In addition, longer intervals since transplantation were associated with increased fibrosis. These data confirm those assembled in Birmingham, United Kingdom, by Evans et al.2 The English cohort included, at 5-year survival, 148 patients still considered pediatric who were followed at the reporting institution. Of these, 3 were judged to be poor candidates for liver biopsy, and 10 declined the procedure. Among the 135 who underwent biopsy prompted not specifically by LFT abnormalities but instead by the study schedule (protocol biopsy), 58 had chronic hepatitis, and 47 of these had substantial fibrosis (4 with cirrhosis). At 10-year survival, 68 patients were eligible for protocol biopsy; 1 was judged to be a poor candidate, and 3 declined the procedure. Of the 64 biopsy specimens obtained, 41 showed chronic hepatitis, and 37 of these had substantial fibrosis (6 with cirrhosis). LFTs did not distinguish between patients with and without hepatitis and fibrosis. These 2 reports thus establish that, as in adults,3 surveillance or protocol biopsy in children will identify inflammation and scarring in the engrafted liver and that these will worsen over time. They also establish that LFT monitoring alone does not reflect the status of the allograft liver in children and that liver biopsy is required for an accurate assessment of that status. Bernadine Healy in 1997 wrote: “Don't order a test if you lack the facts to know how to interpret the result.”4 Is it time to apply Healy's Law in pediatric posttransplant liver care? What shall we do, after all, with the information on the liver's status that we obtain at protocol or surveillance biopsy? Shall we intervene when hepatitis or fibrosis is found, stepping in to augment immunosuppressive regimens, with their side effects? Can we act to improve graft outcome, and if we can, how can we? Neither Evans et al.2 nor Ekong et al.1 tell us. To answer these questions requires that, should protocol biopsy find abnormalities, assignation to intervention or to watchful waiting be at random and that allograft status, with other indices of health or morbidity, be assessed periodically thereafter. Can such a study be justified? Should such a study even be attempted, or should we proceed from the assumption that inflammation and scarring found at protocol biopsy require intervention? Probably no single care team attends enough liver-transplanted children to answer these questions. The Studies of Pediatric Liver Transplantation (SPLIT) consortium5 is at least positioned to consider the questions, and perhaps the study by Ekong et al.,1 confirming the observations of Evans et al.,2 will provide the impetus for SPLIT or another consortium to decide whether it wishes to set the agenda for further work in this field.

The Effect of Recipient-Specific Surgical Issues on Outcome of Liver Transplantation in Biliary Atresia

Biliary atresia (BA), the most common reason for orthotopic liver transplantation (OLT) in children, is often accompanied by unique and challenging anatomical variations. This study examines the effect of surgical-specific issues related to the presence of complex vascular anatomic variants on the outcome of OLT for BA. The study group comprised 944 patients who were enrolled in the Studies of Pediatric Liver Transplantation (SPLIT) registry and underwent OLT for BA over an 11-year period. 63 (6.7%) patients met the study definition of complex vascular anomalies (CVA). Patient survival, but not graft survival, was significantly lower in the CVA group, (83 vs. 93 % at 1-year post-OLT). The CVA group had a significantly higher incidence of all reoperations, total biliary tract complications, biliary leaks and bowel perforation. The most frequent cause of death was infection, and death from bacterial infection was more common in the CVA group. Pretransplant portal vein thrombosis and a preduodenal portal vein were significant predictors of patient survival but not graft survival. This study demonstrates that surgical and technical factors have an effect on the outcome of BA patients undergoing OLT. However, OLT in these complex patients is technically achievable with an acceptable patient and graft survival.

Understanding quality of life for children after liver transplantation: A work in progress

Understanding quality of life for children after liver transplantation: A work in progress

Increasing calories, decreasing morbidity and mortality: Is improved nutrition the answer to better outcomes in patients with biliary atresia?

Increasing calories, decreasing morbidity and mortality: Is improved nutrition the answer to better outcomes in patients with biliary atresia?

Late Graft Loss or Death in Pediatric Liver Transplantation: An Analysis of the SPLIT Database

Late graft loss (LGL) and late mortality (LM) following liver transplantation (LT) in children were analyzed from the studies of pediatric liver transplantation (SPLIT) database. Univariate and multivariate associations between pre- and postoperative factors and LGL and LM in 872 patients alive with their primary allografts 1 year after LT were reviewed. Thirty-four patients subsequently died (LM) and 35 patients underwent re-LT (LGL). Patients who survive the first posttransplant year had 5-year patient and graft survival rates of 94.2% and 89.2%, respectively. Graft loss after the first year was caused by rejection in 49% of the cases with sequelae of technical complications accounting for an additional 20% of LGL. LT for tumor, steroid resistant rejection, reoperation in the first 30 days and >5 admissions during the first posttransplant year were independently associated with LGL in multivariate analysis. Malignancy, infection, multiple system organ failure and posttransplant lymphoproliferative disease accounted for 61.8% of all late deaths after LT. LT performed for FHF and tumor were associated with LM. Patients who are at or below the mean for weight at the time of transplant were also at an increased risk of dying. Frequent readmission was also found to be associated with LM.

Impact of Graft Type on Outcome in Pediatric Liver Transplantation

To examine the outcome of technical variant liver transplant techniques relative to whole organ liver transplantation in pediatric liver transplant recipients. Technical variant liver transplant techniques comprising split, reduced, and live-donor liver transplantation evolved to address the need for timely and size appropriate grafts for pediatric recipients. Analysis of data from the Studies of Pediatric Liver Transplantation (SPLIT) registry, a multicenter database of 44 North American pediatric liver transplant programs. The outcome (morbidity and mortality) of each of the technical variants were compared with that of whole organ recipients. Data were available on 2192 transplant recipients (1183 whole, 261 split, 388 reduced, and 360 live donor). Recipients of all technical variant graft type were significantly younger than whole organ recipients, but on average spent 2.3 months less on the waiting list. Thirty-day post-transplant morbidity was increased for each type of technical variant relative to whole organ (45.1% whole, 66.7% split, 65.5% reduced, 51.9% live-donor). Biliary complications (30 day: 7.5% whole, 18.8% split, 16% reduced, 17.5% live-donor) and portal vein thrombosis (30 day: 3.6% whole, 8% split, 8% reduced, 7.5% live-donor) were more common in all technical variant types. Graft type was an independent predictor of graft loss (death or retransplantation) in a multivariate analysis. Split and reduced (relative risk = 1.74 and 1.77, respectively) grafts had a worse outcome when compared with whole organ recipients. Technical variant techniques expand the pediatric donor pool and reduce time from listing to transplant, but they are associated with increased morbidity and mortality.

Biliary atresia: A transplant perspective

Biliary atresia is the most common single pediatric liver disease leading to liver transplantation (LT) during childhood. Between 1995 and 2002, 42% of children undergoing their first liver transplant while enrolled in the Studies of Pediatric Liver Transplantation (SPLIT) did so for a primary diagnosis of biliary atresia. There have been a number of recent reviews and advances related to the detection, diagnosis, and pathogenesis of biliary atresia. The purpose of this review is to focus on aspects of biliary atresia that are directly relevant to LT as a modality for its treatment. In particular, this review will concentrate on (1) specific indications for LT in the setting of biliary atresia, (2) management issues in children awaiting LT, (3) special surgical approaches in transplantation for biliary atresia, and (4) outcomes after LT. Biliary atresia is a unique disease with a relatively well-characterized clinical course. Careful analysis of the clinical course permits identification of indications for and timing of LT (Table 1). Transplantation decisions should take into consideration therapeutic approaches to the specific indications and complications that have developed. Thus, the following sections will examine both indications for transplantation and the management of those clinical problems.

Biliary Atresia: Clinical Profiles, Risk Factors, and Outcomes of 755 Patients Listed for Liver Transplantation

To test the hypothesis that risk analysis from the time of listing for liver transplantation (LT) focuses attention on areas where outcomes can be improved. Competing outcomes and multivariate models were used to determine significant risk factors for pretransplantation and posttransplantation mortality and graft failure in patients with biliary atresia (BA) listed for LT and enrolled in the Studies of Pediatric Liver Transplantation (SPLIT) registry. Of 755 patients, most were infants (age < 1 year). Significant waiting list mortality risk factors included infancy and pediatric end-stage liver disease (PELD) score > or = 20, whose components were also continuous risk factors. Survival posttransplantation (n=567) was 88% at 3 years. Most deaths were from infection (37%). Posttransplantation mortality risk factors included infant recipients, height/weight < -2 standard deviations (SD), use of cyclosporine versus tacrolimus and retransplantation. Graft failure risks included height/weight < -2 SD, cadaveric partial donors, donor age < or = 5 months, use of cyclosporine versus tacrolimus, and rejection. Referral for LT should be anticipatory for infants with BA with failed portoenterostomies. Failing nutrition should prompt aggressive support. Post-LT risk factors are mainly nonsurgical, including nutrition, the relative risk of infection over rejection, and the choice of immunosuppression.

Immunosuppression in Pediatric Liver and Intestinal Transplantation: A Closer Look at the Arsenal

Immunosuppression in Pediatric Liver and Intestinal Transplantation: A Closer Look at the Arsenal

Posttransplant survival in pediatric fulminant hepatic failure: The SPLIT experience

Pediatric patients with fulminant hepatic failure (FHF) tend to be the sickest and have the most urgent need for a liver transplant. The purpose of this analysis was to identify factors associated with posttransplant survival in this subset of patients. Data on all FHF patients registered in the Studies of Pediatric Liver Transplantation (SPLIT) registry from 1995 to 2002 were analyzed. Demographics such as age, gender, race, weight, and etiology of liver disease were recorded. Pretransplant degree of encephalopathy; intubation; dialysis; laboratory parameters such as serum bilirubin and international normalized ratio of coagulopathy (INR); and type of graft: cadaveric whole, cadaveric technical variant, or living donor were analyzed to determine effects on patient survival. Overall, FHF accounted for 12.9% (141 / 1,092) of primary transplants performed between 1995 and 2002. The etiology of liver disease was unknown in the vast majority of children (126 / 141; 89.4%). Mortality while on the waiting list for FHF children is significantly higher than for children with other liver disease (P < .0001). Six-month survival posttransplant for patients with FHF (74.5%) is significantly lower (P < .0001) than those with chronic liver disease (88.9%). A multivariate model demonstrates that the highest risk group includes those children with grade 4 encephalopathy (P < .0001), infants less than 1 year of age (P = .018), and children requiring dialysis prior to transplantation (P = .002). Pretransplant bilirubin and INR were not significant predictors of posttransplant survival after controlling for the other significant factors. Living donor and split / reduced grafts did not have a significantly increased risk of posttransplant death compared to whole grafts. In conclusion, despite advances in the surgical techniques and changes in organ allocation, pediatric patients with FHF continue to have a high pretransplant mortality and less successful posttransplant survival compared to children with chronic liver disease.