Results after the adoption of a MELD/PELD‐based liver allocation policy in Argentina

In July 2005, Argentina switched from a categorical liver allocation system to a MELD/PELD‐based policy for patients with CLD. To analyze WL outcomes and survival after LT in children. From January 2000 to December 2010, 923 children were registered. Two consecutive five‐yr periods were analyzed and compared: Era I (January 2000–July 2005) (n = 379) and Era II (July 2005–December 31, 2010) (n = 544). All data were prospectively collected and analyzed using the Kaplan–Meier method. After adopting the MELD/PELD system, WL registrations increased by 44% (from 379 to 544) and the number of LT increased by only 24% (from 278 to 365). However, three‐month WL mortality rate (32% to 18%, p < 0.0001, HR 2.002 CI 95% 1.5–2.8) decreased significantly. No significant differences were observed between Era 1 and II in one‐yr post‐LT survival (77.5% vs. 84.1%, p = 0.3053) and in acute re‐LT rate (9% vs. 5%, p = 0.1746). Under the MELD/PELD‐based allocation system in Argentina, mortality on the WL significantly decreased in children with CLD without affecting post‐LT survival, although reduced access to LT was observed.     

Pediatric acute liver failure: Etiology,outcomes, and the role of serial pediatric end‐stage liver disease scores

To describe etiology, short‐term outcomes and prognostic accuracy of serial PELD scores in PALF. Retrospective analysis of children aged ≤16 yr, admitted with PALF under the QLTS, Brisbane, Australia, between 1991 and 2011. PELD‐MELD scores were ascertained at three time points (i) admission (ii), meeting PALF criteria, and (iii) peak value. Fifty‐four children met criteria for PALF, median age 17 months (1 day–15.6 yr) and median weight 10.2 kg (1.9–57 kg). Etiology was known in 69%: 26% metabolic, 15% infective, 13% drug‐induced, 6% autoimmune, and 9% hemophagocytic lymphohistiocytosis. Age <3 months and weight <4.7 kg predicted poor survival in non‐transplanted children. Significant independent predictors of poor outcome (death or LT) were peak bilirubin > 220 μm /L and peak INR > 4. Serial PELD‐MELD scores were higher in the 17 (32%) transplant recipients (mean: [i] 26.8, [ii] 31.8, [iii] 42.6); highest in the 12 (22%) non‐transplanted non‐survivors (mean: [i] 31.6, [ii] 37.2, [iii] 45.7) compared with the 25 (46%) transplant‐free survivors (mean: [i] 25.3, [ii] 26.0, [iii] 30.3). PELD‐MELD thresholds of ≥27 and ≥42 at (ii) meeting PALF criteria and (iii) peak predicted poor outcome (p < 0.001). High peak bilirubin and peak INR predict poor outcome and serial PELD‐MELD is superior to single admission PELD‐MELD score for predicting poor outcome.     

Results of pediatric living donor compared to deceased donor liver transplantation in the PELD/MELD era: Experience from two centers on two different continents

The LDLT option in the pediatric population allows recipients to be transplanted early. A total of 202 consecutive pediatric liver transplants from two different institutions—108 (LDLT) and 94 (DDLT)—were retrospectively compared. Overall, one‐ and three‐yr patient and graft survival were similar between DDLT and LDLT. ACR was greater in recipients of DDLT at one and three yr (50.8% and 61.0%) compared to LDLT (30.8% and 32.2%) (p = 0.002). When the data were stratified according to PELD/MELD score, LDLT with a low score had better one‐ and three‐yr graft survival (96.2% and 96.2%) compared to DDLT (88.2% and 85.2%) (p = 0.02), with comparable patient survival (p = 0.75). Patient and graft survival were similar between DDLT and LDLT in the high PELD/MELD group. Lower incidence of ACR in both low and high PELD/MELD groups was (29.6% and 34.3%) for LDLT compared to DDLT (50.3% and 53.3%, p = 0.002 and p = 0.028, respectively). Regardless of PELD/MELD score, status, age group, and recipient weight, LDLT provides excellent patient and graft survival with a lower incidence of rejection compared to DDLT.     

Lymphocele after pediatric kidney transplantation: Incidence and risk factors

Lymphocele is a well‐known postoperative complication after kidney transplantation. The aim of this study was to analyze time trend incidence, risk factors, and outcome of post‐transplant lymphocele in a large pediatric cohort. This is a retrospective single institution review of 241 pediatric kidney transplants performed from 2000 to 2013. Etiology of end‐stage renal disease, recipient age and gender, transplant year, BMI percentile for age, type of dialysis, living/non‐living related donor, acute rejection, and multiple transplantations were analyzed in association with lymphocele formation. Fourteen of 241 (5.81%) children developed a postoperative lymphocele. There has been a reduction in the incidence of lymphocele after 2006 (3.22% vs. 8.55%, p < 0.05). Significant risk factors for lymphocele were older age (≥11 yr), transplant before 2006, male gender, BMI percentile for age ≥95%, and multiple transplantations (p < 0.05). The one‐yr graft survival was significantly reduced in the group with lymphocele compared with control (81.2% vs. 92.51%, p < 0.04). This is the first pediatric report showing the following risk factors associated with post‐transplant lymphocele: age ≥11 yr, male gender, BMI for age ≥95%, and multiple transplantations. A lymphocele can contribute to graft loss in the first‐year post‐transplant.     

Parental functioning improves the developmental quotient of pediatric liver transplant recipients

Psychomotor development in pediatric liver transplant (LT) recipients depends on several factors. Our aim was to evaluate the importance of parental involvement and family dynamics on psychomotor development by assessing (i) children and parents individually, (ii) the parent–child relationship, and (iii) the correlation between parental functioning and patient outcome, all before and after LT. Age‐appropriate scales were used before and after LT. Twenty‐one patients, 19 mothers, and 16 fathers were evaluated. Developmental quotient (DQ): No subjects scored in the “very good” range. The proportion of children with deficits increased from LT to two yr: 17.6% vs. 28.6%. Subjects 0–2 yr were more likely to have normal DQ at transplant (66.7% vs. 50% for older children). Abnormal DQ was more prevalent two yr post‐LT in children older at LT (p = 0.02). The mother–child relationship was normal in 59% of families pre‐LT and in 67% at two yr. The relationship was more favorable when the child received a transplant as an infant (p = 0.014 at 12 months post‐LT). Normal DQ was associated with higher maternal global functioning score pre‐LT (p = 0.03). Paternal performance scores were higher than maternal scores. Children transplanted after two yr of age suffer greater long‐term deficits than those transplanted as infants.     

Long‐term outcomes and predictors in pediatric liver retransplantation

Historically, 9–29% of pediatric liver transplant recipients have required retransplantation. Although outcomes have improved over the last decade, currently published patient and graft survival remain lower after retransplant than after primary transplant. Data from liver retransplantation recipients at our institution between 1991 and 2013 were retrospectively reviewed. Kaplan–Meier estimates were used to depict patient and graft survival. Predictors of survival were analyzed using a series of Cox proportional hazards models. Predictors were analyzed separately for patients who had “early” (≤30 days after primary transplant) and “late” retransplants. Eighty‐four patients underwent retransplant at a median time of 241 days. Sixty percent had late retransplants. At one, five, and 10 yr, actuarial patient and graft survival were 73%/71%, 66%/63%, and 58%/53%, respectively. Since 2002, patient and graft survival improved to 86%/86% at one yr and 93%/87% at five yr. While operative complications were a common cause of death after earlier retransplants, since 2002, infection has been the only cause of death. Significant morbidities at five‐yr follow‐up include renal dysfunction (15%), diabetes (13%), hypertension (26%), chronic rejection (7%), and PTLD (2%). Current survival after pediatric liver retransplantation has improved significantly, but long‐term immunosuppressant morbidity remains an opportunity for improvement.     

Artificial neural network is highly predictive of outcome in paediatric acute liver failure

Current prognostic models in PALF are unreliable, failing to account for complex, non‐linear relationships existing between multiple prognostic factors. A computational approach using ANN should provide superior modelling to PELD‐MELD scores. We assessed the prognostic accuracy of PELD‐MELD scores and ANN in PALF in children presenting to the QLTS, Australia. A comprehensive registry‐based data set was evaluated in 54 children (32M, 22F, median age 17 month) with PALF. PELD‐MELD scores calculated at (i) meeting PALF criteria and (ii) peak. ANN was evaluated using stratified 10‐fold cross‐validation. Outcomes were classified as good (transplant‐free survival) or poor (death or LT) and predictive accuracy compared using AUROC curves. Mean PELD‐MELD scores were significantly higher in non‐transplanted non‐survivors (i) 37 and (ii) 46 and transplant recipients (i) 32 and (ii) 43 compared to transplant‐free survivors (i) 26 and (ii) 30. Threshold PELD‐MELD scores ≥27 and ≥42, at meeting PALF criteria and peak, gave AUROC 0.71 and 0.86, respectively, for poor outcome. ANN showed superior prediction for poor outcome with AUROC 0.96, sensitivity 82.6%, specificity 96%, PPV 96.2% and NPV 85.7% (cut‐off 0.5). ANN is superior to PELD‐MELD for predicting poor outcome in PALF.     

Outcome of liver re‐transplantation in children—Impact and special analysis of early re‐transplantation

In case of graft failure, re‐LTX is the only life‐saving option but it has been associated with inferior results. This study analyzes the outcome following pediatric re‐LTX with a main focus on the timely relation between initial transplant and re‐LTX. All pediatric LTX at our institution between 2000 and 2010 divided into patients with primary LTX and patients undergoing re‐LTX early (≤30 days) or late (>30 days) after previous LTX were analyzed. Two hundred and ninety‐eight primary LTX(79%), 33 early (9%), and 46 late (12%) re‐LTX were performed. Patient/graft survival was significantly worse for children undergoing early re‐LTX compared to primary LTX and late re‐LTX (p = 0.024/0.001 and p = 0.015/0.03). One‐/five‐yr graft survival rates were 66%/49% for early re‐LTX compared to 86%/76% for late re‐LTX and 90%/74% for primary LTX. The inferior results in children undergoing early re‐LTX were due to events occurring in the first six months with similar survival thereafter. No difference in outcome was evident after adjustment of the groups for high‐urgency status. Outcome was excellent for primary LTX and late re‐LTX, supporting late re‐LTX in children. Early re‐LTX takes an elevated risk of early graft loss and patient death; however, beyond the early postoperative period, the outcome was comparable.     

Orthotopic liver transplantation for children with Alagille syndrome

Arnon R, Annunziato R, Miloh T, Suchy F, Sakworawich A, Hiroshi S, Kishore I, Kerkar N. Orthotopic liver transplantation for children with Alagille syndrome.
Pediatr Transplantation 2010: 14:622–628. © 2010 John Wiley & Sons A/S. Abstract: AGS is an inherited disorder involving the liver, heart, eyes, face, and skeleton. Aim: To determine the outcome of LT in children with AGS compared to those with BA. Methods: Children with AGS and BA who had a LT between 10/1987 and 5/2008 were identified from the UNOS database. Results: Of 11 467 children who received a liver transplant, 461 (4.0%) had AGS and 3056 (26.7%) had BA. One‐ and five‐yr patient survival was significantly lower in patients with AGS in comparison with patients with BA (AGS; 82.9%, 78.4%, BA; 89.9%, 84%, respectively). Early death (<30 days from transplant) was significantly higher in AGS than in BA. One‐ and five‐yr graft survival was significantly lower in AGS than in BA (AGS; 74.7%, 61.5%, BA; 81.6%, 70.0%, respectively). Death from graft failure, neurological, and cardiac complications was significantly higher in patients with AGS than in patients with BA. Serum creatinine at transplant, prior LT, and cold ischemic time >12 h were identified as risk factors for death. Conclusion: Children with AGS were older at the time of LT and their one‐ and five‐yr patient and graft survival were significantly lower compared to BA. Risk factors for poor outcome in AGS after LT were identified.     

Alemtuzumab induction with tacrolimus monotherapy in 25 pediatric renal transplant recipients

ALA induction in transplantation has been shown to reduce the need for maintenance immunosuppression. We report the outcome of 25 pediatric renal transplants between 2007 and 2010 using ALA induction followed by tacrolimus maintenance monotherapy. Patient ages were 1–19 yr (mean 14 ± 4.1 yr). Time of follow‐up was 7–51 months (mean 26 ± 13 months). Tacrolimus monotherapy was maintained in 48% of patients, and glucocorticoids were avoided in 80% of recipients. Mean plasma creatinine and GFR at one yr post‐transplant were 0.88 ± 0.3 mg/dL and 104.4 ± 25 mL/min/1.73m², respectively. One, two, and three‐yr actuarial patient and graft survival rates were 100%. The incidence of early AR (<12 months after transplantation) was 12%, while the incidence of late AR (after 12 months) was 16%. Forty‐four percent of the recipients recovered normal, baseline renal function after an episode of AR, and 44% had persistent renal dysfunction (plasma creatinine 1.0–1.8 mg/dL). One graft was lost four yr after transplantation due to medication non‐compliance. Four (16%) patients developed BK or CMV infection. In our experience, ALA induction with tacrolimus monotherapy resulted in excellent short‐ and mid‐term patient and graft survival in low‐immunologic risk pediatric renal transplant recipients.     

20‐ to 25‐year patient and graft survival following a single pediatric liver transplant—Analysis of the United Network of Organ Sharing database: Where to go from here

To understand factors contributing to liver graft loss and patient death, we queried a national database designed to follow pediatric patients transplanted between 1987 and 1995 till adulthood. A comparison was made to a cohort transplanted between 2000 and 2014. The 5‐, 10‐, 15‐, 20‐, and 25‐year patient survival and graft survival were 95.5%, 93.7%, 89.1%, 80.8%, and 73.1%, and 92.5%, 86.7%, 77.6%, 68.7%, and 62.2%, respectively. The twenty‐year patient/graft survival was significantly worse in those transplanted between 5 and 17 years of age compared to those transplanted at <5 years of age (P < 0.001). For the modern era cohort, the 3‐year patient survival was significantly lower in children transplanted at 16‐17 years of age compared to those transplanted at <5 and 11‐15 years of age (P ≤ 0.02). The 3‐year graft survival was similarly lower in children transplanted at 16‐17 years of age compared to those transplanted at <5, 5‐10, and 11‐15 years of age (P ≤ 0.001). Infection as a cause of death occurred either early or >15 years post‐transplant. Chronic rejection remained the leading cause of graft loss in both cohorts and the commonest indication for retransplantation 20‐25 years following primary transplant. Further research is required to identify modifiable factors contributing to development of chronic rejection.     

Intra‐operative extracorporeal membrane oxygenation use in pediatric lung transplantation – The Zurich experience

There is a lack of data regarding use of ECMO in children undergoing lung transplantation. We evaluated our experience of ECMO in pediatric lung transplant recipients. All patients (<18 yr) who underwent lung transplants between 1997 and 2011 were included (17 children; nine males; median age 16 yr), and the use of intra‐operative ECMO evaluated. Transplant procedures were carried out with intra‐operative ECMO in seven children (all bilateral lung transplants). Demographics of ECMO and non‐ECMO patients were comparable. One child was already on ECMO pre‐operative. Lung graft size reduction was undertaken in five ECMO and four non‐ECMO cases, respectively. Five patients were taken off ECMO intra‐operatively; the other patients were weaned off ECMO within 48 h post‐operatively. Three‐months survival was 100%. By 12 months post‐transplantation, one patient each died in the ECMO and in the non‐ECMO group. At the end of the study, six of seven ECMO cases were still alive (median survival 48.5 months); one patient required a retransplant at 53 months. Our small case series suggests that lung transplant procedures can be safely carried out in selected children on intra‐operative ECMO support; however, our pediatric experience regarding this scenario is very limited but probably almost unique.     

Late acute rejection: Incidence,risk factors,and effect on graft survival and function

Long‐term graft survival and function has not kept pace with short‐term success in kidney transplant (Tx) recipients. LAR ≥6 months post‐Tx may contribute to lack of improvement; risk factors for LAR are not well known. Of 64 Tx recipients followed over six yr, 23 (35.9%) had LAR (LAR group) and 41 had no LAR (no LAR group). Of all variables, significant risk factors for LAR included DGF, (43.4% LAR vs. 14.6% in no LAR group, p = 0.0096); de novo DSA (65.2% vs. 26.8%, p = 0.003); mean COV% of TAC (41.8% vs. 34.6%, p = 0.03); and non‐adherence (34.8% vs. 7.3%, p = 0.0043). DGF and DSA remained statistically significant (p = 0.002 and 0.003, respectively); COV% TAC had borderline significance (p = 0.057), and non‐adherence was not significant on multivariate regression analysis. Patients with LAR had inferior graft survival and function, whereas graft function was stable in the no LAR group over a mean follow‐up of 31.2 months. Patients with de novo DSA and DGF should be considered at risk of LAR; an early diagnosis and treatment of LAR may improve graft survival and function.     

Effect of small donor weight and donor–recipient weight ratio on the outcome of liver transplantation in children

A small donor weight is a risk factor for HAT with potential for graft loss. To test this hypothesis, we evaluated outcomes of pediatric liver transplants utilizing donors <20 kg using the UNOS database from 01/2003 to 01/2012 (n = 1311). All isolated liver transplants with whole organ grafts were included. Recipients were divided into four groups based on donor weight: group 1, donor weight <5 kg (n = 34 [2%]); group 2, 5–10 kg (431 [33%]); group 3, 10–15 kg (560 [43%]); and group 4, 15–20 kg (286 [22%]). Actuarial patient survival for the first year post‐transplant was significantly lower in groups 1 and 2 compared to groups 3 and 4 (p = 0.002), similarly the one‐yr graft function (p < 0.0001). The difference was due to graft loss within the first month for groups 1 and 2. HAT was significantly higher in groups 1 and 2 compared to others (p = 0.0006). Logistic regression analysis demonstrated donor weight as the most predictive factor with analysis of the ROC curve showing a cutoff point at 7.8 kg. The donor–recipient weight ratio did, in none of the models, gain statistical significance.     

Mortality after pediatric kidney transplantation in England – a population‐based cohort study

The aim of this study was to explore mortality after pediatric kidney transplantation in England over the last decade. We used data from HES to select all kidney transplant procedures performed in England between April 2001 and March 2012. Data linkage analysis was performed with the ONS to identify all deaths occurring among this study cohort. Data for 1189 pediatric recipients were compared to 17 914 adult recipients (number of deaths, 33 vs. 2052, respectively, p < 0.001), with median follow‐up 4.4 yr (interquartile range 2.2–7.3 yr). There was no difference in mortality within the pediatric cohort; age 0–1 (n = 25, patient survival 100.0%), age 2–5 (n = 198, patient survival 96.0%), age 6–12 (n = 359, patient survival 97.5%), and age 13–18 (n = 607, patient survival 97.4%), respectively (p = 0.567). The most common causes of death were renal (n = 8, 24.2%), infection (n = 6, 18.2%), and malignancy (n = 5, 15.2%). All deaths from malignancy were secondary to PTLD. In a fully adjusted Cox regression model, only white ethnicity was significantly associated with risk of pediatric mortality post‐kidney transplantation (hazard ratio 2.7, 95% confidence interval [1.0–7.3], p = 0.047). To conclude, this population‐based cohort study confirms low mortality after pediatric kidney transplantation with short follow‐up.     

Impact of congenital heart disease on outcomes of pediatric heart‐lung transplantation

HLT is reserved for children with cardiopulmonary disease not amendable to alternative therapies. Children with CHD with or without ES may be considered for HLT. Outcomes of HLT in this population are not well described. To test the hypothesis that CHD without ES is associated with worse graft survival and identify factors associated with poor outcome, a retrospective analysis of the UNOS database was performed. One hundred and seventy‐eight pediatric HLTs were performed between 1987 and 2011. CHD was the diagnosis in 65 patients, of which 34 had CHD without ES. Patients with CHD without ES had decreased patient survival (median 1.31 yr) compared with CHD with ES (4.80 yr, p = 0.05). On multivariable analysis, the following were associated with graft failure: CHD without ES (adjusted HR 1.69, 95% CI 1.09–2.62), younger age (1.04, 1.01–1.08), pretransplant mechanical ventilation (1.75, 1.01–3.06), pretransplant ECMO (3.07, 1.32–7.12), pretransplant PRAs (1.53, 1.06–2.20), and transplant era (1.85, 1.16–2.94). In children with CHD who require HLT, underlying physiology influences outcomes. Those without ES have a worse prognosis. The diagnosis of CHD without ES and preoperative factors may inform decisions in a complex patient population.     

Basiliximab with delayed introduction of calcineurin inhibitors as a renal‐sparing protocol following liver transplantation in children with renal impairment

Renal impairment is frequently compromised in patients with end‐stage liver disease and is associated with increased long‐term mortality post‐LT. In contrast to CNI, basiliximab is an immunosuppressive agent with minimal nephrotoxic potential. This study reviews the experience of a single pediatric liver transplant center's renal‐sparing approach with the use of basiliximab and MMF to compensate for delayed entry of CNI in children with renal impairment at the time of organ availability. There were no differences in renal function between pediatric patients with and without pre‐LT renal impairment within the first year (cGFR: 135 mL/min/1.73 m² vs. 144 mL/min/1.73 m²; p = 0.56) or at 5–8 yr following LT, (129 mL/min/1.73 m² vs. 130 mL/min/1.73 m²; p = 0.97). In addition, there was no difference in ACR rates (50% vs. 43%, p = 0.62) between patients in the basiliximab group and those patients receiving standard CNI and steroid strategies. The utilization of a renal‐sparing approach with basiliximab alongside delayed entry and lower early target trough levels of CNI in children with renal impairment at the time of LT is safe and maintains excellent long‐term kidney function.     

The effect of MMF dose and trough levels on adverse effects in pediatric heart transplant recipients

Limited pharmacokinetic and safety data exist for MMF in pediatric HTR. Previously targeted MPA‐TL are 1.5–3.0 μg/mL. The objective of this study was to assess the outcomes targeting MPA‐TL of 0.8–2.0 μg/mL in pediatric HTR. MPA‐TL were retrospectively collected 2–12 months post‐transplant. Acute rejection, infection, leukopenia, and GI complaints were then correlated with MPA‐TL. A total of 355 MPA‐TL from 22 HTR were included. Median age was 2.5 yr. Primary indication for transplant was dilated cardiomyopathy (64%). Mean MPA‐TL was 1.7 ± 0.9 μg/mL. African American patients received significantly higher doses (702 ± 235 mg/m²) compared with other races (p = 0.035). Leukopenia was less common in patients with SUB MPA vs. others (p = 0.01). MMF was discontinued for GI complaints in one patient and leukopenia in two patients. One SUB patient had acute rejection, and one SUP patient had infection. One‐yr survival was 100%. Targeting a lower range for MPA‐TL was not associated with significant rejection or infection. Despite lower MPA‐TL, MMF was discontinued in 3/22 patients for adverse effects.     

Kidney transplant in pediatric patients with severe bladder pathology

The aim of the current study was to compare results in pediatric renal transplantation of patients with and without SBP. Between 2001 and 2013, a total of 168 kidney transplants were performed at our center. A retrospective analysis was performed and recipients were divided into two groups: NB and SBP. Incidence of surgical complications after procedure, and graft and patient survival were evaluated. A total of 155 recipients (92%) with complete data were analyzed, and 13 recipients that had had previous bladder surgeries were excluded (11 with VUR surgery and two with previous kidney transplants), of the 155 recipients: 123 (79%) patients had NB, and 32 (21%) patients had SBP, with a median follow‐up of 60 (1–137) and 52 (1–144) months, respectively. Among post‐transplant complications, UTI (68.8% vs. 23%, p < 0.0001) and symptomatic VUR to the graft (40.6% vs. 7.3%, p < 0.0001) were significantly higher in the SBP group. There was no significant difference in overall graft and patient survival between groups. Renal transplantation is safe in pediatric recipients with SBP; however, urologic complications such as UTI and VUR were significantly higher in this group. Graft and patient survival was similar in SBP and NB groups.