Organ-Specific Comorbidities Are Associated With Distinct Complications After Liver Transplantation for Biliary Atresia.

Although transplant outcomes for biliary atresia (BA) have improved, there are few data to predict the risk of specific posttransplant complications. We therefore defined the impact of comorbidities in BA on posttransplant outcomes. Patients enrolled in the Society of Pediatric Liver Transplantation registry from 2011 to 2019 (n = 1034) were grouped by comorbidities of >1.0% incidence: any supplemental feeding, dialysis, other abdominal surgery (not Kasai portoenterostomy [KPE]), hepatopulmonary syndrome, and cardiac disease requiring intervention. Demographic and outcome data were compared using the Kruskal-Wallis, chi-square, and log-rank tests. Cox proportional hazards models and binary logistic regression were performed for modeling. Patients with BA with comorbidities comprised 77% (n = 799) of our cohort and had evidence of greater medical acuity, including higher calculated Pediatric End-Stage Liver Disease scores and hospitalizations in the intensive care unit before transplant (P < 0.001 for both) versus those without comorbidities. After transplant, patients with BA with comorbidities had more graft loss (P = 0.02), longer initial hospitalization and intubation (P < 0.001 for both), and increased rates of reoperation (P = 0.001) and culture-proven infection (P < 0.001) within 30 days after transplant. Only patients with BA with comorbidities on supplemental feed had increased rates of patient death (P = 0.02). Multivariate analysis identified lower z weight and higher creatinine as risk factors for graft and patient loss in patients with BA with comorbidities. Prior KPE was protective against culture-proven infection and vascular complications within 30 and 90 days, respectively. Patients with BA with comorbidities have evidence of higher medical acuity at transplant and reduced graft survival; however, they overall did not experience greater incidence of patient death. Our data provide organ-system-specific data to risk-stratify patients with BA and posttransplant outcomes.

Left lateral segment pediatric liver transplantation: a 25 year experience at Mount Sinai.

BACKGROUND: Outcomes of left lateral segment (LLS) grafts in pediatric recipients were compared between living (LD-LLS) and deceased donor (DD-LLS) grafts. METHODS: 195 LLS grafts (99DD-LLS-96LD-LLS) were analyzed with a median follow-up of 9.1years. The primary endpoints were overall patient/graft survival. RESULTS: LD-LLS grafts were younger (0.9vs.1.4years, p = 0.039), more likely to have a fulminant liver failure (17.9%vs.5.3%,p = 0.002), less likely to have a metabolic disorder (6.3%vs.25.5%,p = 0.002), and less likely to be undergoing retransplantation (5.3% vs.16.2%,p = 0.015). There was a trend toward decreased hepatic artery thrombosis in LD-LLS grafts (6.6% vs. 15.5%,p = 0.054). No differences in the overall biliary complications occurred. The LD-LLS group had prolonged survival compared to the DD-LLS group with 10-year survival rates of 81%, and 74% (p = 0.005), respectively. LD-LLS grafts had longer graft survival compared to DD-LLS grafts (10-year graft survival 85%vs.67%,p = 0.005). Recipient age >1year (HR 2.39,p = 0.026), aortic reconstruction (HR 2.12,p = 0.046) and vascular complication (HR 3.12,p < 0.001) were independent predictors of poor patient survival. Non-biliary liver disease (HR 2.17,p = 0.015), DD-LLS (HR 2.06,p = 0.034) and vascular complication (HR 4.61,p < 0.001) were independent predictors of poor graft survival. CONCLUSION: The use of SLT remains a viable option with excellent long-term outcomes. We show improved graft and patient survival with living donor grafts.

Severe Acute Respiratory Syndrome Coronavirus-2 Infection in Children With Liver Transplant and Native Liver Disease: An International Observational Registry Study.

OBJECTIVE: Increased mortality risk because of severe acute respiratory syndrome coronavirus-2 (SARS-CoV2) infection in adults with native liver disease (LD) and liver transplant (LT) is associated with advanced age and comorbid conditions. We aim to report outcomes for children with LD and LT enrolled in the NASPGHAN/SPLIT SARS-CoV2 registry. METHODS: In this multicenter observational cohort study, we collected data from 91 patients <21 years (LD 44, LT 47) with laboratory-confirmed SARS-CoV2 infection between April 21 and September 17, 2020. RESULTS: Patients with LD were more likely to require admission (70% vs 43% LT, P = 0.007) and pediatric intensive care unit (PICU) management (32% vs 4% LT, P = 0.001). Seven LD patients required mechanical ventilation (MV) and 2 patients died; no patients in the LT cohort died or required MV. Four LD patients presented in pediatric acute liver failure (PALF), 2 with concurrent multisystem inflammatory syndrome in children (MIS-C); all recovered without LT. Two LD patients had MIS-C alone and 1 patient died. Bivariable logistic-regression analysis found that patients with nonalcoholic fatty LD (NAFLD) (odds ratio [OR] 5.6, P = 0.02) and LD (OR 6.1, P = 0.01, vs LT) had higher odds of severe disease (PICU, vasopressor support, MV, renal replacement therapy or death). CONCLUSIONS: Although not directly comparable, LT recipients had lower odds of severe SARS-CoV2 infection (vs LD), despite immunosuppression burden. NAFLD patients reported to the registry had higher odds of severe SARS-CoV2 disease. Future controlled studies are needed to evaluate effective treatments and further stratify LD and LT patients with SARS-CoV2 infection.

Improved Outcomes for Liver Transplantation in Patients with Biliary Atresia Since Pediatric End-Stage Liver Disease Implementation: Analysis of the Society of Pediatric Liver Transplantation Registry.

OBJECTIVE: To identify changes in demographics, outcomes, and risk factors for patient and graft loss in patients with biliary atresia undergoing liver transplantation since Pediatric End-Stage Liver Disease implementation (2002). STUDY DESIGN: Demographics and outcomes were compared between patients enrolled in the Society of Pediatric Liver Transplantation registry before (n = 547) and after (n = 1477) 2002. Kruskal-and χ2 Wallis tests identified significant differences between eras. Risk factors for patient and graft loss after 2002 were determined by Cox regression model analysis of time to event data. RESULTS: Significant patient differences after 2002 support increasing disease severity including more status 1 patients and those with a derived Model for End-Stage Liver Disease/Pediatric End-Stage Liver Disease score of greater than 30 awaiting transplant. Both patient and graft survival improved after 2002 from 90% to 97% and 81% to 90%, respectively (primary transplant; P < .0001). Significant differences in complications within 30 days included reduced relisting for transplant, rejection, culture-positive infection, repeat operation, hepatic artery thrombosis, portal vein thrombosis, and death/transplant before discharge. Multivariable analysis identified deceased technical variant vs whole graft and retransplantation predictive for patient death, hazard ratios of 4.041 and 8.308, respectively. Deceased technical variant vs whole graft (hazard ratio, 1.963) and donor age 0-5 months vs 1-17 years (hazard ratio, 5.525) were risk factors for graft loss. CONCLUSIONS: The overall outcomes of patients receiving liver transplantation for patients with biliary atresia have improved since 2002 despite evidence of increased disease severity at the time of transplant. Risk factors impacting post-transplant morbidity and mortality in patients with biliary atresia are now mainly surgical including donor variables.

Management of Wilson Disease Diagnosed in Infancy: An Appraisal of Available Experience to Generate Discussion.

Increased access to molecular genetic testing is changing the demographics for diagnosing inherited disorders and imposing new challenges for medical management. Wilson disease (WD), typically diagnosed in older children and adults, can now be detected in utero and in infants (children younger than 24 months, including neonates) via genetic testing. An evidence-based approach to management of these neonates and extremely young children, who are typically asymptomatic, has been hampered by lack of clinical experience. We present a case of an infantile diagnosis of WD, review available experience, and discuss current trends in antenatal genetic testing of parents and fetus that may lead to a very early diagnosis of WD. Based on physiological and nutritional considerations, we propose an algorithmic approach to management of infantile WD as a starting point for further discussion. Future collaboration amongst specialists is essential to identify evidence-based approaches and best practice for managing treatment of infants with genetically diagnosed WD.

Neurodevelopmental Outcomes in Preschool and School Aged Children With Biliary Atresia and Their Native Liver.

OBJECTIVES: The aim of the study was to assess neurodevelopmental outcomes among children with biliary atresia (BA) surviving with their native liver at ages 3 to 12 years and evaluate variables that associate with neurodevelopment. METHODS: Participants (ages 3-12 years) in a prospective, longitudinal, multicenter study underwent neurodevelopmental testing with Weschler Preschool and Primary Scale of Intelligence, 3rd edition (WPPSI-III, ages 3-5 years) and Weschler Intelligence Scale for Children, 4th edition (WISC-IV, ages 6-12 years). Continuous scores were analyzed using Kolmogorov-Smironov tests compared with a normal distribution (mean = 100 ±â€Š15). Effect of covariates on Full-Scale Intelligence Quotient (FSIQ) was analyzed using linear regression. RESULTS: Ninety-three participants completed 164 WPPSI-III (mean age 3.9) and 51 WISC-IV (mean age 6.9) tests. WPPSI-III FSIQ (104 ±â€Š14, P < 0.02), Verbal IQ (106 ±â€Š14, P < 0.001), and General Language Composite (107 ±â€Š16, P < 0.001) distributions were shifted higher compared with test norms. WISC-IV FSIQ (105 ±â€Š12, P < 0.01), Perceptual Reasoning Index (107 ±â€Š12, P < 0.01), and Processing Speed Index (105 ±â€Š10, P < 0.02) also shifted upwards. In univariate and multivariable analysis, parent education (P < 0.01) was a significant predictor of FSIQ on WPPSI-III and positively associated with WISC-IV FSIQ. Male sex and higher total bilirubin and gamma glutamyl transferase (GGT) predicted lower WPPSI-III FSIQ. Portal hypertension was predictive of lower WISC-IV FSIQ. CONCLUSIONS: This cohort of children with BA and native liver did not demonstrate higher prevalence of neurodevelopmental delays. Markers of advanced liver disease (higher total bilirubin and GGT for age ≤5 years; portal hypertension for age ≥6) correlate with lower FSIQ and may identify a vulnerable subset of patients who would benefit from intervention.

Safety and Efficacy of Ledipasvir-Sofosbuvir With or Without Ribavirin for Chronic Hepatitis C in Children Ages 6-11.

Currently, there are no interferon-free treatments available for hepatitis C virus (HCV)-infected patients younger than 12 years. We evaluated the safety and effectiveness of the all-oral regimen ledipasvir-sofosbuvir ± ribavirin in HCV-infected children aged 6 to <12 years. In an open-label study, patients aged 6 to <12 years received ledipasvir 45 mg-sofosbuvir 200 mg as two fixed-dose combination tablets 22.5/100 mg once daily, with or without ribavirin, for 12 or 24 weeks, depending on HCV genotype and cirrhosis status. The primary efficacy endpoint was sustained virologic response 12 weeks after therapy (SVR12). Twelve patients underwent intensive pharmacokinetic sampling to confirm the appropriateness of the ledipasvir and sofosbuvir dosages. Ninety-two patients were enrolled (88 genotype 1, 2 genotype 3, and 2 genotype 4), with a median age of 9 years (range, 6-11). Most were perinatally infected (97%) and treatment-naive (78%). Two were confirmed to have cirrhosis, while the degree of fibrosis was unknown in 55 patients. The overall SVR12 rate was 99% (91/92; 95% confidence interval, 94%-100%). The single patient not reaching SVR relapsed 4 weeks after completing 12 weeks of treatment. The most common adverse events were headache and pyrexia. One patient had three serious adverse events, which were considered to be not related to study treatment: tooth abscess, abdominal pain, and gastroenteritis. The area under the concentration-time curve and maximum concentration values for sofosbuvir, its primary metabolite GS-331007, and ledipasvir were within predefined pharmacokinetic equivalence boundaries (50%-200%) compared to values in adults in phase 2/3 of the ledipasvir and sofosbuvir studies. Conclusion: Ledipasvir-sofosbuvir was well tolerated and highly effective in children 6 to <12 years old with chronic HCV.

Neurodevelopmental Outcome of Young Children with Biliary Atresia and Native Liver: Results from the ChiLDReN Study.

OBJECTIVES: To assess neurodevelopmental outcomes among participants with biliary atresia with their native liver at ages 12 months (group 1) and 24 months (group 2), and to evaluate variables predictive of neurodevelopmental impairment. STUDY DESIGN: Participants enrolled in a prospective, longitudinal, multicenter study underwent neurodevelopmental testing with either the Bayley Scales of Infant Development, 2nd edition, or Bayley Scales of Infant and Toddler Development, 3rd edition. Scores (normative mean = 100 ± 15) were categorized as ≥100, 85-99, and <85 for χ2 analysis. Risk for neurodevelopmental impairment (defined as ≥1 score of <85 on the Bayley Scales of Infant Development, 2nd edition, or Bayley Scales of Infant and Toddler Development, 3rd edition, scales) was analyzed using logistic regression. RESULTS: There were 148 children who completed 217 Bayley Scales of Infant and Toddler Development, 3rd edition, examinations (group 1, n = 132; group 2, n = 85). Neurodevelopmental score distributions significantly shifted downward compared with test norms at 1 and 2 years of age. Multivariate analysis identified ascites (OR, 3.17; P = .01) and low length z-scores at time of testing (OR, 0.70; P < .04) as risk factors for physical/motor impairment; low weight z-score (OR, 0.57; P = .001) and ascites (OR, 2.89; P = .01) for mental/cognitive/language impairment at 1 year of age. An unsuccessful hepatoportoenterostomy was predictive of both physical/motor (OR, 4.88; P < .02) and mental/cognitive/language impairment (OR, 4.76; P = .02) at 2 years of age. CONCLUSION: Participants with biliary atresia surviving with native livers after hepatoportoenterostomy are at increased risk for neurodevelopmental delays at 12 and 24 months of age. Those with unsuccessful hepatoportoenterostomy are >4 times more likely to have neurodevelopmental impairment compared with those with successful hepatoportoenterostomy. Growth delays and/or complications indicating advanced liver disease should alert clinicians to the risk for neurodevelopmental delays, and expedite appropriate interventions. TRIAL REGISTRATION: Clinicaltrials.gov: NCT00061828 and NCT00294684.

Sofosbuvir and ribavirin in adolescents 12-17 years old with hepatitis C virus genotype 2 or 3 infection.

Children with chronic hepatitis C virus infection have limited treatment options. We evaluated the all-oral combination of sofosbuvir and ribavirin in adolescents aged 12-17 with hepatitis C virus genotype 2 or 3 (ClinicalTrials.gov NCT02175758). Fifty-two patients received sofosbuvir 400 mg once daily and weight-based ribavirin twice daily for 12 (genotype 2) or 24 (genotype 3) weeks. The pharmacokinetics of sofosbuvir and its metabolite GS-331007 were evaluated by intensive plasma sampling at day 7 in the first 10 patients enrolled and by sparse sampling in all patients throughout treatment. The primary efficacy endpoint was the percentage of patients with a sustained virologic response 12 weeks after treatment (SVR12). The median age of patients was 15 years, and 75% had genotype 3. Eighty-three percent of patients were treatment-naive, and 73% were infected by vertical transmission. Forty percent were assessed as not having cirrhosis; the remainder did not have a cirrhosis determination. Overall, SVR12 was achieved by 98% of patients (51/52; 95% confidence interval, 90%-100%). SVR12 rates were 100% (13/13) for patients with genotype 2 and 97% (38/39) for those with genotype 3. The single patient who did not achieve SVR12 was lost to follow-up after achieving SVR4. The most commonly reported adverse events were nausea (27%) and headache (23%). When compared with the exposure in adults treated in phase 2 and 3 sofosbuvir studies, the area under the curve and maximum concentration for sofosbuvir and GS-331007 in adolescents were within predefined pharmacokinetic equivalence boundaries of 50%-200%. CONCLUSION: Sofosbuvir and ribavirin was safe and highly effective in adolescents with chronic hepatitis C virus genotype 2 or 3 infection. (Hepatology 2017;66:1102-1110).

Analysis of surgical interruption of the enterohepatic circulation as a treatment for pediatric cholestasis.

To evaluate the efficacy of nontransplant surgery for pediatric cholestasis, 58 clinically diagnosed children, including 20 with Alagille syndrome (ALGS), 16 with familial intrahepatic cholestasis-1 (FIC1), 18 with bile salt export pump (BSEP) disease, and 4 others with low γ-glutamyl transpeptidase disease (levels <100 U/L), were identified across 14 Childhood Liver Disease Research Network (ChiLDReN) centers. Data were collected retrospectively from individuals who collectively had 39 partial external biliary diversions (PEBDs), 11 ileal exclusions (IEs), and seven gallbladder-to-colon (GBC) diversions. Serum total bilirubin decreased after PEBD in FIC1 (8.1 ± 4.0 vs. 2.9 ± 4.1 mg/dL, preoperatively vs. 12-24 months postoperatively, respectively; P = 0.02), but not in ALGS or BSEP. Total serum cholesterol decreased after PEBD in ALGS patients (695 ± 465 vs. 457 ± 319 mg/dL, preoperatively vs. 12-24 months postoperatively, respectively; P = 0.0001). Alanine aminotransferase levels increased in ALGS after PEBD (182 ± 70 vs. 260 ± 73 IU/L, preoperatively vs. 24 months; P = 0.03), but not in FIC1 or BSEP. ALGS, FIC1, and BSEP patients experienced less severely scored pruritus after PEBD (ALGS, 100% vs. 9% severe; FIC1, 64% vs. 10%; BSEP, 50% vs. 20%, preoperatively vs. >24 months postoperatively, respectively; P < 0.001). ALGS patients experienced a trend toward greater freedom from xanthomata after PEBD. There was a trend toward decreased pruritus in FIC1 after IE and GBC. Vitamin K supplementation increased in ALGS after PEBD (33% vs. 77%; P = 0.03). Overall, there were 15 major complications after surgery. Twelve patients (3 ALGS, 3 FIC1, and 6 BSEP) subsequently underwent liver transplantation. CONCLUSION: This was a multicenter analysis of nontransplant surgical approaches to intrahepatic cholestasis. Approaches vary, are well tolerated, and generally, although not uniformly, result in improvement of pruritus and cholestasis. (Hepatology 2017;65:1645-1654).

Autoimmune hemolytic anemia: An unusual presentation of hemophagocytic lymphohistiocytosis in a pediatric post-liver transplant patient.

Hemophagocytic lymphohistiocytosis (HLH), a rare condition characterized by immune dysfunction with uncontrolled activation of macrophages and hypersecretion of cytokines, has only been reported in a small number of pediatric patients following solid organ transplant (SOT). The diagnosis of HLH after SOT is especially difficult, as several of the diagnostic criteria, including fever, splenomegaly, and cytopenias, are nonspecific and can be seen with other post-transplant complications. Autoimmune hemolytic anemia (AIHA) has also been reported after pediatric SOT and is thought to be related to immunosuppression, specifically tacrolimus. Although HLH and AIHA have been separately described following SOT, there have been no reports of them occurring together in post-liver transplant (LT) patients. We report the first case of autoimmune hemolysis as the presenting symptom of HLH in a pediatric post-LT patient.

Pediatric Liver Transplant Teams Coping With Patient Death.

OBJECTIVES: Coping with patient death among pediatric liver transplant teams has received little attention despite general recognition of the potentially negative emotional consequences associated with such loss. The purpose of this study was to investigate the ways in which members of pediatric liver transplant teams cope with the death of patients on the waitlist and post-transplant and the institutional resources available to facilitate this coping. METHODS: Participants included 120 physicians, nurses, and mental health professionals from multiple transplant centers across the United States. Participants completed an online questionnaire that assessed the availability of formal coping resources at their institutions, informal sources of support used to cope with patient death, and as indices of coping, bereavement, and emotional exhaustion symptoms experienced. RESULTS: Debriefing, the most commonly offered support, was available to about half (55.8%) of the sample; yet, nearly all respondents (98.3%) indicated that debriefing would be useful. On average, bereavement and emotional exhaustion levels were comparable to normative data, but patterns of coping varied based on participants' position within the transplant team. For participants who reported that debriefing was available at their institutions, emotional exhaustion was lower. CONCLUSIONS: Overall, formal supports were inconsistently offered to pediatric transplant team members. Team members expressed high acceptability for debriefing, which has been associated with benefits in other populations, and findings indicated better coping in the transplant setting when it was offered.

Pediatric liver transplantation for fulminant hepatic failure secondary to intentional iron overdose.

Acute iron poisoning may lead to life-threatening hepatotoxicity. We present the cases of two pediatric patients with hepatotoxicity following intentional iron ingestion that progressed rapidly to fulminant hepatic failure despite treatment with deferoxamine. Liver transplantation was lifesaving in both patients. These cases emphasize the need for a high index of suspicion for iron ingestion, close monitoring for liver toxicity, and timely consideration for liver transplantation.

Liver Transplantation for Children With Primary Sclerosing Cholangitis and Autoimmune Hepatitis: UNOS Database Analysis.

OBJECTIVES: Autoimmune hepatitis (AIH) and primary sclerosing cholangitis (PSC) are progressive immune-mediated inflammatory diseases that may require liver transplant (LT). Outcomes in children undergoing LT for these diseases are poorly studied in the pediatric end-stage liver disease era. We aimed to characterize the outcome of LT in children with AIH and PSC. METHODS: Children 18 years or younger with PSC or AIH who had a first, isolated LT from 2002 to 2012 were identified from the United Network for Organ Sharing database. Graft and patient outcomes were studied. RESULTS: A total of 174 children with AIH and 113 with PSC were transplanted in the study period. One-year patient survival was 95.4% for AIH and 97.3% for PSC. Five-year patient survival was 91.4% for AIH and 92.9% for PSC. Patient survival was not significantly different between the 2 groups. Forty-four (25.2%) children with AIH were listed as status 1 for transplant (fulminant hepatic failure at presentation or acute-on-chronic disease). Patients transplanted as status 1 had significantly lower patient survival compared with patients transplanted with AIH and end-stage liver disease. The one- and five-year graft survival rates were not significantly different between patients with AIH and PSC. CONCLUSION: Children with AIH transplanted as status 1 had significantly lower patient survival rates but similar graft survival rates to children with chronic AIH. Children transplanted for AIH versus PSC showed no significant differences in patient or graft survival at both 1 and 5 years.

Fulminant Liver Failure in a Child With ß-Thalassemia on Deferasirox: A Case Report.

Deferesirox (DFX), an oral chelating agent, is used to treat chronic iron overload in several hematological diseases such as ß-thalassemia, sickle cell disease, and myelodysplastic anemia. DFX is generally well tolerated with the exception of gastrointestinal disturbances and rash, although cases of renal toxicity, as well as acute and chronic liver failure, have been reported in adults and children. Here we describe a 3-year-old girl with ß-thalassemia undergoing treatment with DFX who presented with acute liver failure and Fanconi's syndrome. It is important for pediatric gastroenterologists, hepatologists, and hematologists to be aware that the commonly used drug DFX can lead to acute liver failure in children, and liver function should be monitored closely in all patients taking DFX.

Children with Hepatitis C: The Impact of Disease and Treatment on Patients, Caregivers and Families.

PURPOSE: Previous research on children with HCV has examined patient psychosocial outcomes but little is known about the impact of HCV and its prolonged treatment, which includes weekly injections and oral medications for 6-12 months, on caregivers and families. The present study aimed to address this gap. DESIGN AND METHODS: Using a case series design (N=10), baseline distress levels of individuals and families as well as changes during HCV treatment were examined. A brief patient, caregiver, and family assessment packet was given before and immediately after treatment, but before the final outcome of treatment was known. During the study period, 10 families at our site began treatment for HCV. Each family was given a battery assessing patient quality of life, (the Pediatric Quality of Life Inventory; PedsQL), caregiver distress related to their child's illness (Impact of Events Scale; IES), and overall family functioning (Family Assessment Device; FAD). RESULTS: At baseline, patients displayed poorer quality of life than population norms, caregiver distress was elevated and family functioning was also in the "stressed" range. After treatment, all parameters worsened. CONCLUSIONS: In conclusion, in this case series of patients in treatment for HCV, significant psychosocial distress was noted for individuals and families and this was exacerbated over the course of treatment. PRACTICE IMPLICATIONS: Caregivers may benefit from additional support given the implications of HCV and grueling nature of its treatment. Broadly, the impact of continuous intensive treatments on families perhaps should be monitored.

Total Serum Bilirubin within 3 Months of Hepatoportoenterostomy Predicts Short-Term Outcomes in Biliary Atresia.

OBJECTIVES: To prospectively assess the value of serum total bilirubin (TB) within 3 months of hepatoportoenterostomy (HPE) in infants with biliary atresia as a biomarker predictive of clinical sequelae of liver disease in the first 2 years of life. STUDY DESIGN: Infants with biliary atresia undergoing HPE between June 2004 and January 2011 were enrolled in a prospective, multicenter study. Complications were monitored until 2 years of age or the earliest of liver transplantation (LT), death, or study withdrawal. TB below 2 mg/dL (34.2 µM) at any time in the first 3 months (TB <2.0, all others TB ≥ 2) after HPE was examined as a biomarker, using Kaplan-Meier survival and logistic regression. RESULTS: Fifty percent (68/137) of infants had TB < 2.0 in the first 3 months after HPE. Transplant-free survival at 2 years was significantly higher in the TB < 2.0 group vs TB ≥ 2 (86% vs 20%, P < .0001). Infants with TB ≥ 2 had diminished weight gain (P < .0001), greater probability of developing ascites (OR 6.4, 95% CI 2.9-14.1, P < .0001), hypoalbuminemia (OR 7.6, 95% CI 3.2-17.7, P < .0001), coagulopathy (OR 10.8, 95% CI 3.1-38.2, P = .0002), LT (OR 12.4, 95% CI 5.3-28.7, P < .0001), or LT or death (OR 16.8, 95% CI 7.2-39.2, P < .0001). CONCLUSIONS: Infants whose TB does not fall below 2.0 mg/dL within 3 months of HPE were at high risk for early disease progression, suggesting they should be considered for LT in a timely fashion. Interventions increasing the likelihood of achieving TB <2.0 mg/dL within 3 months of HPE may enhance early outcomes. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00061828 and NCT00294684.

Liver transplantation for pediatric inherited metabolic disorders: Considerations for indications, complications, and perioperative management.

LT is an effective therapeutic option for a variety of IEM. This approach can significantly improve the quality of life of patients who suffer from severe disease manifestations and/or life-threatening metabolic decompensations despite medical/dietary management. Due to the significant risks for systemic complications from surgical stressors, careful perioperative management is vital. Even after LT, some disorders require long-term dietary restriction, medical management, and monitoring of metabolites. Successful liver transplant for these complex disorders can be achieved with disease- and patient-specific strategies using a multidisciplinary approach. In this article, we review indications, complications, perioperative management, and long-term follow-up recommendations for IEM that are treatable with LT.

Liver Transplantation for Biliary Atresia: Is There a Difference in Outcome for Infants?

OBJECTIVES: Liver transplantation (LT) in children with biliary atresia (BA) is often performed because of poor bile drainage, complications of biliary cirrhosis, or recurrent cholangitis. Poor bile drainage after a Kasai hepatoportoenterostomy is the primary driver for LT in infancy. The aim of the present study was to compare the clinical characteristics and outcome of first isolated liver transplantation for infants with BA who underwent transplant before 2 years of age (transplanted at infancy [TAI]) with children transplanted later in life (age 2-<18 years = transplanted at childhood [TAC]). METHODS: Children with BA who underwent LT between 2002 and 2012 were identified from the United Network for Organ Sharing Standard Transplant Analysis and Research data set files. RESULTS: A total of 1818 children underwent first isolated liver transplantation for BA (TAI 1408 [77.4%]; TAC 410 [22.6%]). One and 5-year patient survival of the TAI and TAC patients was 95.2%, 93.8%, and 97.8 %, 97.1%, respectively (P < 0.01 for both periods). One and 5-year graft survival of the TAI and TAC patients was 87.6%, 84.6 % and 93.2%, 90.7%, respectively (P < 0.01 for both periods). Removal from the waitlist for disease progression or death was significantly higher for TAI compared with TAC (120 patients [6.3%] vs 21 [3.7%], P = 0.02). Cold ischemic time was found to be the prognostic factor for death after LT in TAI, whereas being on life support was a poor prognostic factor in TAC by multivariate risk factor analysis. CONCLUSIONS: The vast majority of transplants for BA occur in children <2 years of age. Younger patients with BA had significantly higher waitlist and posttransplant mortality. Given the consistently poorer outcomes, there is an urgent need to find methods to improve bile drainage after the Kasai hepatoportoenterostomy.

Roux-en-Y intussusception after pediatric liver transplant - A case report.

Small bowel obstruction in a pediatric patient following liver transplant often results from adhesions, hernias, or post-transplant lymphoproliferative disease. Here, we present an unusual and previously unreported entity - Roux-en-Y intussusception in an eight-yr-old female several years after liver transplantation. Although a rare complication, Roux-en-Y intussusception should be considered as a potential etiology in the patient presenting with bowel obstruction, with specific attention to acute presentation accompanying jaundice.