Risk factors for early and late biliary complications in pediatric liver transplantation

BC are a common source of morbidity after pediatric LT. Knowledge about risk factors may help to reduce their incidence. Retrospective analysis of BC in 116 pediatric patients (123 LT) (single institution, 05/1990–12/2011, medium follow‐up 7.9 yr). One‐, five‐, and 10‐yr survival was 91.1%, no patient died of BC. Prevalence and risk factors for anastomotic and intrahepatic BC were examined. There were 29 BC in 123 LT (23.6%), with three main categories: 10 (8.1%) primary anastomotic strictures, eight (6.5%) anastomotic leaks, and three (2.4%) intrahepatic strictures. Significant risk factors for anastomotic leaks were total operation time (increase 1.26‐fold) and early HAT (<30 days post‐LT; increase 5.87‐fold). Risk factor for primary anastomotic stricture was duct‐to‐duct choledochal anastomosis (increase 5.96‐fold when compared to biliary‐enteric anastomosis). Risk factors for intrahepatic strictures were donor age >48 yr (increase 1.09‐fold) and MELD score >30 (increase 1.2‐fold). To avoid morbidity from anastomotic BC in pediatric LT, the preferred biliary anastomosis appears to be biliary‐enteric. Operation time should be kept to a minimum, and HAT must by all means be prevented. Children with a high MELD score or receiving livers from older donors are at increased risk for intrahepatic strictures.     

A child with unresectable biliary rhabdomyosarcoma: 48‐month disease‐free survival after liver transplantation

We describe here a two‐yr‐old boy with biliary RMS successfully treated by chemotherapy and LT. The child presented with obstructive jaundice at 20 months of age. A mildly vascularized, non‐calcified, partially cystic lesion was visualized in the left hepatic lobe. Solid infiltration of the common bile duct and of both left and right hepatic ducts was suspected. Liver biopsy suggested a botryoid‐type embryonal RMS originating from the biliary tract. After extrahepatic spread of the tumor was excluded, a biliary drain was applied and neoadjuvant chemotherapy was started. After the treatment, although reduced in volume, the mass was still unresectable without aggressive surgery and gross residual disease. LT with a reduced segment II/III graft was performed four months after diagnosis. The patient received six cycles of adjuvant chemotherapy, and he is alive and recurrence‐free 48 months post‐transplantation. A posteriori, the transplant might have possibly been avoided with an aggressive resection with biliary reconstruction. Nevertheless, although the risk of the transplant has to be balanced against the chemoresponsiveness of the tumor, the four‐yr disease‐free survival of this patient suggests that, when coupled with effective chemotherapy, transplantation might be considered a potential treatment for unresectable biliary RMS.     

Survival outcomes scores (SOFT,BAR, and Pedi‐SOFT) are accurate in predicting post‐liver transplant survival in adolescents

SOFT and BAR scores utilize recipient, donor, and graft factors to predict the 3‐month survival after LT in adults (≥18 years). Recently, Pedi‐SOFT score was developed to predict 3‐month survival after LT in young children (≤12 years). These scoring systems have not been studied in adolescent patients (13–17 years). We evaluated the accuracy of these scoring systems in predicting the 3‐month post‐LT survival in adolescents through a retrospective analysis of data from UNOS of patients aged 13–17 years who received LT between 03/01/2002 and 12/31/2012. Recipients of combined organ transplants, donation after cardiac death, or living donor graft were excluded. A total of 711 adolescent LT recipients were included with a mean age of 15.2±1.4 years. A total of 100 patients died post‐LT including 33 within 3 months. SOFT, BAR, and Pedi‐SOFT scores were all found to be good predictors of 3‐month post‐transplant survival outcome with areas under the ROC curve of 0.81, 0.80, and 0.81, respectively. All three scores provided good accuracy for predicting 3‐month survival post‐LT in adolescents and may help clinical decision making to optimize survival rate and organ utilization.     

Measles,mumps, rubella (vaccine) and varicella vaccines in pediatric liver transplant: An initial analysis of post‐transplant immunity

Varicella and measles infection represents a significant source of morbidity and mortality for pediatric LT recipients. We evaluated the prevalence and correlates of post‐transplant immunity in pediatric LT recipients previously immunized against measles (n = 72) and varicella (n = 67). Sixteen of seventy‐two (22%) patients were measles non‐immune, and 42/67 (63%) were varicella non‐immune after LT. Median time from LT to titers for measles and varicella was 4.0 and 3.3 years, respectively. In the measles cohort, non‐immune patients received fewer pretransplant vaccine doses (P = 0.026) and were younger at both time of vaccination (P = 0.006) and LT (P = 0.004) compared with immune patients. Upon multivariable analysis, weight > 10 kg at LT (OR 5.91, 95% CI 1.27‐27.41) and technical variant graft (OR 0.07, 95% CI 0.01‐0.37) were independently, significantly associated with measles immunity. In the varicella cohort, non‐immune patients received fewer pretransplant vaccine doses (P = 0.028), were younger at transplant (P = 0.022), and had less time lapse between their last vaccine and transplant (P = 0.012) compared with immune patients. Upon multivariate analysis, time > 1 year from last vaccine to LT was independently, significantly associated with varicella immunity (OR 3.78, CI 1.30‐11.01). This study demonstrates that non‐immunity to measles and varicella is a prevalent problem after liver transplantation in children and identifies 3 unique risk factors for non‐immunity in this high‐risk population.     

Overweight,central obesity,and cardiometabolic risk factors in pediatric liver transplantation

PTMS describes the presence of ≥3 cardiometabolic risk factors that include obesity, hypertension, dyslipidemia, and IR. The prevalence of the clustering of ≥3 cardiometabolic risk factors or central obesity has not been studied in pediatric LT recipients. Single‐center, cross‐sectional study. Inclusion criteria: LT recipients 2–18 yr‐old, at least one yr post‐LT. Exclusion criteria: recipients of liver retransplants or multivisceral transplants. Eighty‐seven patients were identified. Median age was 9.8 yr (range 2–18), median time since LT was 6.9 yr (range 1–17). The most common indication for LT was biliary atresia (56%), and the most frequently used immunosuppressant was tacrolimus (80%). The prevalence of overweight and obesity was 21% and 5%, respectively. Central obesity affected 14%, hypertension 44%, IR 27%, low HDL 20%, and hypertriglyceridemia 39% of patients. The prevalence of ≥3 cardiometabolic risk factors was 19%. Fifty percent of the overweight/obese patients had ≥3 risk factors. Time since transplant, immunosuppression and renal function were not different between those with <3 or ≥3 risk factors. Clustering of cardiometabolic risk factors is prevalent in pediatric LT recipients, suggesting an increased risk of future CV events.     

Pulmonary complications after liver transplantation in children: risk factors and impact on early post‐operative morbidity

Liver transplantation (LT) is associated with high post‐operative morbidity, despite excellent survival rates. With this retrospective study, we report the incidence of early and late pulmonary complications (PC) after LT, identify modifiable risk factors for PC and analyzed the role of PC in post‐operative ventilation duration and hospital length of stay. In a series of 79 children (0‐16 years) with LT over a 12 years period, early (<3 months post‐LT) and/or late (>3 months post‐LT) PC occurred in 68 patients (86%). Sixty‐four percent (64%) developed early major complications such as pulmonary edema, atelectasis, or pleural effusion. Atelectasis requiring an intervention (P ≤ .02), pulmonary edema (P ≤ .02), or elevated PELD/MELD scores (P = .05) were associated with an increase in total ventilation duration and length of stay in the ICU. Risk factors for early PC included preoperative hypoxemia (P = .005), low serum albumin at LT admission (P = .003), or early rejection (P = .002). About 20% of patients experienced late PC of which 81% were infections. Risk factor assessment prior to LT may ultimately help reduce early PC thereby possibly minimizing post‐operative morbidity and ICU length of stay.     

Health utility and quality of life in pediatric liver transplant recipients

To measure HU and HRQOL in pediatric liver transplant (LT) recipients, a cross‐sectional study of patient‐parent dyads was conducted. Direct HU were assessed in 48 adolescents ≥12 years using SG and TTO techniques. Indirect HU were measured by Health Utility Index 2 and HUI3 for subjects ≥12 years and CHU9D for ≥7 years. Patients reported HRQOL using PedsQL? GC and PedsQL? TM. A total of 108 dyads participated (55.6% female; 73.2% Caucasian; 42.6% biliary atresia; 35.2% living donor; 37.0% Medicaid). Mean age at survey was 13.6 ± 3.5 years, and time from LT was 8.9 ± 4.9 years. 61.2% were on monotherapy, 25 (23.2%) had acute rejection within 3 years, and 15 (13.9%) had a biliary obstruction within 5 years. Mean indirect HU and HRQOL scores by child report were lower than norms (P < .001). LRD recipients had higher PedsQL? GC, PedsQL? TM, and HUI3 scores (P < .01). HU in pediatric LT recipients are lower than norms. Availability of HU scores for post‐transplant health states will enable measurement of quality‐adjusted life years for future comparative effectiveness studies.     

Total internal biliary diversion during liver transplantation for type 1 progressive familial intrahepatic cholestasis: a novel approach

LT for PFIC type 1 is often complicated by postoperative diarrhea and recurrent graft steatosis. A 26‐month‐old female child with cholestatic jaundice, pruritus, diarrhea, and growth retardation revealed total bilirubin 9.1 mg/dL, gamma‐glutamyl transpeptidase 64 IU/L, and TBA 295.8 μmol/L. Genetic analysis confirmed ATP8B1 defects. A LT (segment 2, 3 graft) from the heterozygous father was performed. Biliary diversion was performed by a 35‐cm jejunum conduit between the graft hepatic duct and the mid‐transverse colon. Stools became pigmented immediately. Follow‐up at 138 days revealed resolution of jaundice and pruritus and soft‐to‐hard stools (6–8 daily). Radioisotope hepato‐biliary scintigraphy (days 26, 68, and 139) confirmed unobstructed bile drainage into the colon (t_1/2 34, 27, and 19 minutes, respectively). Contrast meal follow‐through at day 62 confirmed the absence of any colo‐jejuno‐hepatic reflux. At 140 days, contrast follow‐through via the biliary stent revealed patent jejuno‐colonic anastomosis and satisfactory transit. Graft biopsy at LT, 138 days, and 9 months follow‐up revealed comparable grades of macrovesicular steatosis (<20%). TIBD during LT may be a clinically effective stoma‐free biliary diversion and may prevent recurrent graft steatosis following LT for PFIC type 1.     

Intrahepatic cholangiocarcinoma as a rare secondary malignancy after allogeneic hematopoietic stem cell transplantation for childhood acute lymphoblastic leukemia: A case report

Secondary malignancies are a significant cause of non‐relapse mortality in patients who undergo allogeneic HCT. However, secondary liver cancer is rare, and ICC following HCT has never been reported in the literature. Secondary solid cancers typically have a long latency period, and cholangiocarcinoma is classically a malignancy occurring in older individuals. Here, we report the first case of secondary ICC, which presented just 3 years after HCT in a young adult with a history of childhood ALL. A 26‐year‐old male with history of precursor B‐cell ALL presented with asymptomatic elevated liver function tests 3 years after HCT. Laboratories were indicative of biliary obstruction. ERCP showed focal biliary stricturing of the common and left hepatic ducts. MRCP revealed left intrahepatic duct dilatation, suggestive of intrahepatic obstructing mass. Additional workup lead to a clinical diagnosis of ICC. The patient underwent left hepatectomy with extrahepatic bile duct resection and portal lymphadenectomy. Surgical pathology was consistent with moderately differentiated cholangiocarcinoma. Our case illustrates a rare SMN following HCT for ALL. It is the first case report of ICC occurring as a secondary cancer in this patient population. Although cholangiocarcinoma is characteristically diagnosed in the older population, it must remain on the differential for biliary obstruction in post‐HCT patients.     

Tacrolimus‐related seizure after pediatric liver transplantation – A single‐center experience

To identify the risk factors for new‐onset seizures after pediatric LT and to assess their clinical implications and long‐term prognosis. The clinical and laboratory data of 27 consecutive children who underwent LT from January 2007 to December 2010 in our center were analyzed retrospectively. Patients were divided into seizures group and a non‐seizures group. Pre‐operative, intra‐operative, and post‐operative data were collected. Seizures occurred in four children, an incidence of 14.8%. All exhibited generalized tonic–clonic seizures within the first two wk after LT. Univariate analysis showed that the risk factors associated with seizures after pediatric LT included gender, pediatric end‐stage liver disease score before surgery, Child–Pugh score before surgery, serum total bilirubin after surgery, and trough TAC level. Multivariate analysis showed that trough TAC level was the only independent risk factor associated with the seizures. All children who experienced seizures survived with good graft function and remained seizure‐free without anti‐epileptic drugs over a mean follow‐up period of 33.7 ± 14.6 months. High trough TAC level was the predominant factor that contributed to seizures in the early post‐operative period after pediatric LT. High PELD and Child‐Pugh scores before LT and high post‐operative serum Tbil may be contributory risk factors for TAC‐related seizures.     

Late T cell–mediated rejection may contribute to poor outcomes in adolescents and young adults with liver transplantation

Although poor long‐term graft survival in LT in AYA is recognized, detailed epidemiological data are still lacking. L‐TCMR may have poor outcomes. This study aimed to provide a detailed, epidemiological assessment of the association between AYA age and rejection. L‐TCMR was defined in this study as TCMR with central vein or perivenular inflammation occurring later than 3 months after LT. A total of 342 patients who survived for at least 3 months after LT between 2005 and 2015 were enrolled. The AYA group (10‐24 years) was compared with the C group (less than 10 years), and the incidence and outcomes of L‐TCMR were analyzed. In total, 342 patients had LT; 38 of these were AYA with the mean follow‐up period of 6.7 years. A total of 304 patients in C group had a mean follow‐up period of 6.3 years (P = .28). The incidence of L‐TCMR in AYA group was significantly higher than in C group (15.8% vs 4.6%, P = .006). The time to L‐TCMR after LT was significantly shorter in AYA group (P = .01). Neither patient survival nor the incidence of non‐adherence differed significantly between the groups (P = .18 and P = .89). The number of additional immunosuppressants after L‐TCMR was significantly higher in the AYA group (P = .04). A high incidence of L‐TCMR was observed in AYA group irrespective of non‐adherence. AYA patients with L‐TCMR should be followed carefully due to the poor results of post‐treatment biopsy and the need for intensive immunosuppressive therapy.     

Factors predicting health‐related quality of life in pediatric liver transplant recipients in the functional outcomes group

Data from 997 pediatric LT recipients were used to model demographic and medical variables as predictors of lower levels of HRQOL. Data were collected through SPLIT FOG project. Patients were between 2 and 18 yr of age and survived LT by at least 12 months. Parents and children (age ≥ 8 yr) completed PedsQL? 4.0 Generic Core and CF Scales at one time point. Demographic and medical variables were obtained from SPLIT. HRQOL scores were categorized as “poor” based on lower 25% of scores for each measure. Logistic regression models were generated. Single‐parent households (OR 1.94, CI 1.13–3.33, p = 0.017), anti‐seizure medications (OR 3.99, CI 1.26–12.70, p = 0.019), and number of days hospitalized (OR 1.03, CI 1.01–1.06, p = 0.0067) were associated with lower self‐reported HRQOL. Parent data identified increasing age at transplant, age 5–12 yr at survey, hospitalization >21 days at LT, re‐operations, diabetes, and growth failure at LT as additional predictors of generic HRQOL. Male gender, single‐parent households, higher bilirubin levels at LT, and use of anti‐seizure medication predicted lower cognitive function scores. HRQOL following pediatric LT is related to medical and demographic variables.     

Liver transplantation in children with metabolic diseases: The studies of pediatric liver transplantation experience

Arnon R, Kerkar N, Davis MK, Anand R, Yin W, González‐Peralta RP for the SPLIT Research Group. Liver transplantation in children with metabolic diseases: The studies of pediatric liver transplantation experience.
Pediatr Transplantation 2010: 14:796–805. © 2010 John Wiley & Sons A/S. Abstract: Metabolic diseases are the second largest indication for LT in children after BA. There are limited data on the long‐term post‐transplant outcome in this unique group of patients. Therefore, our aim was to assess post‐liver transplant outcomes and to evaluate risk factors for mortality and graft loss in children with metabolic disorders in comparison to those with non‐metabolic diagnoses. We reviewed all patients enrolled in the SPLIT registry. Between 1995 and 2008, 446 of 2997 (14.9%) children enrolled in SPLIT underwent liver transplant for metabolic diseases. One‐yr and five‐yr patient survival for children with metabolic diseases was 94.6% and 88.9% and for those with other diseases 90.7% and 86.1% (log‐rank p = 0.05), respectively. One‐yr and five‐yr graft survival for children with metabolic disorders was 90.8% and 83.8%, and for those with other diseases 85.4% and 78.0% (log‐rank p = 0.005), respectively. Children with metabolic diseases were less likely to experience gastrointestinal complications (5.6% vs. 10.7%, p = 0.001), portal vein thrombosis (2.9% vs. 5.2%, p = 0.04), and reoperations within 30 days post‐transplant (33.4% vs. 37.8%, p = 0.05) than those with other indications. In conclusion, children who underwent liver transplant for metabolic disease had similarly excellent patient survival as, and better graft survival than, those who received a liver allograft for other indications.     

Risk factors for neurological complications and their correlation with survival following pediatric liver transplantation

Despite the improved outcomes of LT, post‐operative NCs remain a significant cause of morbidity and mortality. The aim of the study was to identify the incidence of and risk factors for NCs in children who underwent LT. The medical records of pediatric patients who underwent LT at Asan Medical Center Children's Hospital between January 1994 and December 2010 were retrospectively analyzed. The onset and types of NC and pretransplant variables associated with NC were evaluated. We identified 190 children (85 boys [44.7%], 105 girls [55.3%]) of mean age 4.1 ± 4.7 yr, who underwent LT. Forty‐six NCs occurred in 41 (21.6%) patients after LT, the most common being seizures (n = 13, 28.3%) and encephalopathy (n = 10, 21.7%). Of the 46 NCs, 24 (52.2%) occurred within three months after LT. Multivariate analysis showed that primary liver disease, preoperative neurological problems, preoperatively higher serum creatinine concentration, and graft failure were significant risk factors for NCs. The survival rate was significantly lower for patients with NCs than for those without (p < 0.001). NCs after pediatric LTs were common and associated with a higher mortality rate in our study. Close monitoring and appropriate risk management may improve the long‐term outcomes of pediatric patients who undergo LT.     

Late allograft fibrosis in pediatric liver transplant recipients: Assessed by histology and transient elastography

Late allograft fibrosis in LT recipients can cause graft dysfunction and may result in re‐transplantation. TE is a non‐invasive tool for the assessment of liver fibrosis. We aimed to evaluate the prevalence of allograft fibrosis in pediatric LT recipients, identify factors associated with allograft fibrosis, and determine the diagnostic value of TE, compared to histology. All children who underwent LT for ≥3 years were included. TE was performed for LSM in all patients. LSM of ≥7.5 kPa was considered as abnormal and suggestive of allograft fibrosis. Percutaneous liver biopsy was performed when patients had abnormal LSM and/or abnormal LFTs. Histological fibrosis was diagnosed when METAVIR score ≥F1 or LAF scores ≥1. TE was performed in 43 patients and 14 (32.5%) had abnormal LSM suggestive of allograft fibrosis. Histological fibrosis was identified in 10 of the 15 patients (66.7%) who underwent percutaneous liver biopsy and associated findings included chronic active HBV infection (n = 3), and late acute rejection (n = 3). Multivariate analysis showed that graft age was significantly associated with allograft fibrosis (OR = 1.22, 95% CI: 1.05‐1.41, P = 0.01). In conclusion, late allograft fibrosis is common in children undergoing LT for ≥3 years and associated with graft age. HBV infection and late acute rejection are common associated findings. Abnormal TE and/or LFTs may guide physicians to consider liver biopsy for the detection of late allograft fibrosis in LT children.     

Outcome of duct‐to‐duct vs. Roux‐en‐Y hepaticojejunostomy biliary anastomoses in below 15‐kg pediatric liver transplant recipients

The best type of biliary anastomosis to use in lower weight pediatric liver transplant recipients is debatable. In this study, we share a single center's experience comparing the rate of anastomotic biliary complications based on the type of biliary anastomosis performed in this population of patients. A retrospective review of pediatric liver transplants for recipients weighing <15 kg from 11/2003 till 12/2011 was performed. Patients were grouped based on the type of biliary anastomosis into two groups: duct‐to‐duct (d‐d) and Roux‐en‐Y hepaticojejunostomy (h‐j) anastomoses. A total of 24 patients (12 males, 12 females) with a mean age of 26 ± 20 months and a mean weight of 9.27 ± 2.63 kg (range = 5.3–13.9 kg) were studied. All anastomotic complications occurred in patients who received left lateral segments. No statistical differences were found in the post‐operative biliary (p = 0.86) or vascular (p = 0.99) complications between the two groups. Acknowledging the limited sample size, our data suggest that duct‐to‐duct anastomosis can be performed safely in pediatric liver transplantation recipients weighing below 15 kg.     

Biliary strictures in pediatric liver transplant recipients – Early diagnosis and treatment results in excellent graft outcomes

Anderson CD, Turmelle YP, Darcy M, Shepherd RW, Weymann A, Nadler M, Guelker S, Chapman WC, Lowell JA. Biliary strictures in pediatric liver transplant recipients – Early diagnosis and treatment results in excellent graft outcomes.
Pediatr Transplantation 2010: 14:358–363. © 2009 John Wiley & Sons A/S. Abstract: Biliary complications in pediatric LT are important causes of morbidity and graft loss. We examined our recent pediatric LT experience to determine the outcome of post‐LT biliary complications and their relationship to graft type. All initially isolated LTs performed at our institution between January 1, 2000 and August 20, 2007 were reviewed. Recipient data, donor type, graft survival, and biliary complications data were examined. Of 66 LTs, 32 patients received whole organ grafts, and 34 received partial grafts; 11 split, seven reduced size, and 16 live donors. Seventy‐seven percent of patients had biliary reconstruction using a RYH. Overall, 17 (26%) developed biliary complications, and 15 were diagnosed within six months post‐LT. Live donor and split allografts had more biliary complications than reduced size or whole allografts (50% and 36% vs. 0% and 16%, respectively). Seventy‐one percent responded to percutaneous or endoscopic treatment. Five failed initial non‐operative management and required reoperation (one retransplantation). These data suggest that biliary strictures occur most frequently in live donor and split allografts and that non‐operative therapy is highly successful. Partial grafts are essential in pediatric LT, and a high clinical suspicion for biliary complications combined with aggressive and early diagnosis and therapy rarely results in graft loss.     

Educational and learning morbidity in pediatric heart transplant recipients: A pediatric heart transplant society study

Educational development is an important component of quality of life for children with heart transplant. Aims include determining prevalence of and risk factors for modified education placement in a large representative sample of pediatric heart transplant recipients. Participants included 1495 patients (age 6‐18 years) from the PHTS database. Data on education placement and clinical predictors were collected at listing and at 1 and 3 years post‐transplant. At listing, 88% of patients were in typical education placement, while 12% were in modified education. Males (P = .02), those with CHD (P < .0001), those with non‐private insurance (P < .0001), and those with longer hospital stay (P = .001) were more likely to be in a modified education placement at time of listing. Age, race, listing status, mechanical support, and waitlist time were not significantly associated with placement. The prevalence of typical education placement was similar (87% at 1‐year and 86% at 3‐year) post‐transplant. Predictors of modified education placement at 3‐year follow‐up included placement at listing (OR = 12.9 [95% CI 7.6‐21.9], P < .0001), non‐private insurance (OR = 2.0 [95% CI 1.3‐3.2], P = .001), CHD (OR = 1.8 [95% CI 1.1‐2.7, P = .01), history of post‐transplant infection (OR = 1.9 [95% CI 1.2‐2.9, P = .007), and number of post‐transplant infections (OR = 1.3 [95% CI 1.1‐1.5, P = .002). Among pediatric heart transplant recipients, males, those with non‐private insurance, those with CHD, and those who experience post‐transplant infections are at greatest risk for modified academic placement, which persists for several years post‐transplant and deserves targeted intervention.     

Living‐donor liver transplantation for mild Zellweger spectrum disorder: Up to 17 years follow‐up

Mild Zellweger spectrum disorder, also described as Infantile Refsum disease, is attributable to mutations in PEX genes. Its clinical course is characterized by progressive hearing and vision loss, and neurodevelopmental regression. Supportive management is currently considered the standard of care, as no treatment has shown clinical benefits. LT was shown to correct levels of circulating toxic metabolites, partly responsible for chronic neurological impairment. Of three patients having undergone LT for mild ZSD, one died after LT, while the other two displayed significant neurodevelopmental improvement on both the long‐term (17 years post‐LT) and short‐term (9 months post‐LT) follow‐up. We documented a sustained improvement of biochemical functions, with a complete normalization of plasma phytanic, pristanic, and pipecolic acid levels. This was associated with stabilization of hearing and visual functions, and improved neurodevelopmental status, which has enabled the older patient to lead a relatively autonomous lifestyle on the long term. The psychomotor acquisitions have been markedly improved as compared to their affected siblings, who did not undergo LT and exhibited a poor neurological outcome with severe disabilities. We speculate that LT performed before the onset of severe sensorineural defects in mild ZSD enables partial metabolic remission and improved long‐term clinical outcomes.     

Factors associated with immune hemolytic anemia after pediatric liver transplantation

Immune‐mediated hemolytic anemia following SOT is a rare disorder, the risk factors for which are unknown. Our purpose was to analyze a seemingly increased incidence in our center with the aim to identify predisposing factors. This recipients single‐center retrospective study reviewed the medical records of 96 pediatric LT between 2000 and 2013. IHA was defined as acute anemia with a positive direct antiglobulin test. Seven cases of immune‐mediated hemolytic anemia were identified (incidence 8.5%). Three cases presented during the first 3 months following LT (early IHA), and 4 presented later (late IHA). All patients with late IHA required rituximab. Using univariate analysis, the following factors were associated with IHA onset: BA (P = .04), younger age (P = .04), and the use of IGL‐1 preservation solution (P = .05). Late IHA was associated with viral infections occurring beyond 3 months following LT, younger age, and BA (P = .01). Overall, CMV infection was associated with the development of both early and late IHA: CMV‐negative recipients who received an organ from a CMV‐positive donor were more likely to develop IHA (P = .035), and de novo CMV infection during the first year post‐LT was associated with late IHA (P = .03). IHA is a rare complication following pediatric LT, occurring more frequently in younger patients and patients with an initial diagnosis of BA. CMV‐negative recipients and patients who experience a de novo CMV infection in the first year following LT seem particularly vulnerable. IGL‐1 preservation solution may be associated with an increased likelihood of developing IHA, a novel finding which warrants further investigation.