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Importance: Alpha1-antitrypsin (AAT) deficiency is a common, but an underdiagnosed genetic condition, affecting 1 in 1500 individuals. It can present insidiously with liver disease in children. Although clinical practice guidelines exist for the management of AAT deficiency, especially with regards to pulmonary involvement, there are no published recommendations that specifically relate to the management of the liver disease and monitoring for lung disease associated with this condition, particularly in children. Objective: To review the literature on the management of AAT deficiency-associated liver disease in adults and children. Evidence Review: A systematic search for articles indexed in PubMed and published was undertaken. Some earlier selected landmark references were included in the review. Search terms included: "alpha1-antitrypsin deficiency"; "liver disease"; "end-stage liver disease"; "liver transplantation" and "preventative management". Recommendations for the management of children with suspected or confirmed AAT deficiency were made according to the Strength of Recommendation Taxonomy scale. Findings: Liver complications arising from AAT deficiency result from the accumulation of mutated AAT protein within hepatocytes. Liver disease occurs in 10% of children, manifested by cholestasis, pruritus, poor feeding, hepatomegaly, and splenomegaly, but the presentation is highly variable. A diagnostic test for AAT deficiency is recommended for these children. Baseline liver function tests should be obtained to assess for liver involvement; however, the only curative treatment for AAT deficiency-associated liver disease is organ transplantation. Conclusion and Relevance: There should be a greater vigilance for AAT deficiency testing among pediatricians. Diagnosis should prompt assessment of liver involvement. Children with AATdeficiency- associated liver disease should be referred to a liver specialist and monitored throughout their lifetimes for the symptoms of AAT-deficiency-related pulmonary involvement.

Introduction: Patients with Fontan circulation often develop multiorgan dysfunction. Obesity is a risk factor for systemic complications in the general population, but the impact of obesity in Fontan circulation is unclear. This study investigates the impact of increased BMI on end-organ function in Fontan survivors. Methods: Single center data from patients 13 years and older with Fontan circulation were retrospectively collected from June 2018 to May 2020. Weight at clinic visit was categorized as normal or overweight/obese by WHO BMI-for-age classifications. End-organ function between normal and overweight patients was assessed. The relationship between overweight and measures of end-organ function were modeled via multivariable regression analyses controlling for age, sex, race, heterotaxy, time since Fontan, ventricular function, and atrioventricular valve (AVV) regurgitation. Results: Among 75 patients (median age 18 [15, 26] years), 24 (32%) were overweight or obese. Age, race, duration since Fontan, oxygen saturation, and dominant ventricle did not differ between groups. There were significantly more overweight females (p= 0.02). Overweight patients had significantly lower GFR (p= 0.01), lower predicted peak VO2 (p= 0.02), and higher systemic vascular resistance (SVR) (p= 0.02) than normal weight patients. Duration since Fontan (β= 0.38, p = 0.02) and overweight (β= -0.35, p = 0.03) were independently associated with GFR. Female sex (β= -0.42, p < 0.01) and overweight were independently associated with lower predicted peak VO2. Overweight was independently associated with presence of high SVR (OR = 7.5, p= 0.03). Other tested variables for hepatic (MELD-XI score, liver stiffness), cardiovascular (cardiac index, Fontan pressure, ventricular and AVV function), pulmonary, bone, and hematologic function did not significantly differ between groups. Conclusions: Overweight/obese BMI is common in aging Fontan patients and is significantly associated with worse renal function, exercise capacity, and elevated SVR. These findings suggest a possible relationship between weight, vascular changes, and renal perfusion. Further studies are needed to investigate this mechanism and the impact on Fontan patient outcome.

A 2-year-old male with arginosuccinate lyase deficiency underwent left lateral segment liver transplantation complicated by “orphan duct syndrome (Celik et al., 2019) [1]” and biliary leak. After revision of the Roux-en-Y anastomosis, biliary drainage was still impaired. The excluded bile duct was diagnosed and a biliary restoration (or neo-duct) using a combined endoscopic and percutaneous approach was created by Gastroenterology and Interventional Radiology. To our knowledge, this case report represents the first combined endoscopic-percutaneous biliary restoration procedure performed in a pediatric patient.

BACKGROUND: Diarrhea is a common problem in the pediatric post-solid organ transplant and post-hematopoietic stem cell transplant populations. Infectious etiology incidences are poorly defined, and the possibility of multi-organism positivity is often uninvestigated. The aim of this study is to utilize stool multiplex GIP assays to compare the PTP and NTP regarding the incidence and profiles of single-organism and multi-organism infectious diarrhea. METHODS: A single-center retrospective review was conducted, investigating stool multiplex GIP panel results over a more than 3-year period, for pediatric patients. Assays test for 23 viral, bacterial, and protozoal organisms. RESULTS: Positive assays in the PTP and NTP were 70/101 (69.3%) and 962/1716 (56.1%), respectively (P = .009). Thirty-two percent (32/101) of assays within the PTP were multi-organism positive, significantly more than 14.8% (254/1716) in the NTP (P < .00001). There was no significant difference in the incidence of single-organism positives, 37.6% (38/101) in PTP and 41.3% (708/1716) in the NTP. The PTP demonstrated a statistically significantly higher incidence of the following organisms within multi-agent positive GIPs (P < .05 for each): Clostridioides difficile, Cryptosporidium, EPEC, norovirus, and sapovirus. CONCLUSIONS: The pediatric PTP demonstrates higher incidence of positive GIPs, higher rate of multi-organism positivity, and unique infectious organism incidence profiles. These data can provide a framework for understanding organism-specific pathogenicity factors, assessing the clinical impact of enteric co-infection, and understanding the utility of this testing modality in this unique population.

We present the unique case of a 15-month-old male born with biliary atresia and situs inversus totalis and disrupted inferior vena cava who underwent a successful liver transplantation. The patient had previously undergone a failed Kasai procedure and presented with persistent hyperbilirubinemia. The patient was transplanted with a left lateral segment donor having standard arterial anatomy. Technical considerations included identifying completely replaced arterial anatomy in the recipient from the superior mesenteric artery and creating a branch patch between the gastroduodenal artery and HA, anastomosing the donor left hepatic vein to confluences of the donor left, middle, and right hepatic veins, using a "lazy-S" configuration of portal vein anastomosis, and suspending the allograft to the abdominal wall. Post-operatively, his liver function tests and total bilirubin normalized and he progressed to tolerating an oral diet with tube-feed supplementation.