Perioperative fatal pulmonary embolism in a pediatric liver transplant recipient.

Patients with cirrhotic liver disease are in a state of fluctuating hemostatic balance. Hepatic synthetic dysfunction is commonly complicated by coagulation disorders that constitute an important parameter of most prognostic scores. The dominant feature of this dysfunction is bleeding tendencies, but cirrhotic patients may also exhibit inappropriate clotting and pro-coagulation placing them at risk for thromboembolism. We present a case of perioperative fatal pulmonary embolism in an 8-year-old patient with biliary cirrhosis secondary to drug-induced vanishing bile duct syndrome undergoing a deceased donor liver transplant. The massive pulmonary embolism occurred intra-operatively after reperfusion of the donor liver. Despite the initiation of extracorporeal membrane oxygenation, the postoperative course was complicated by bleeding and the patient expired. This unique case highlights the need for venous thromboembolism prevention by screening and prophylaxis prior to liver transplant in at least a subpopulation of pediatric patients. While the risk of thrombosis postoperatively in pediatrics patients is well known, the preoperative risk is less frequently described and deserves attention and practice changing action.

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.

Pain resolution and glucose control in pediatric patients with chronic pancreatitis after total pancreatectomy with islet auto-transplantation.

BACKGROUND: Chronic pancreatitis (CP) and acute recurrent pancreatitis (ARP) in pediatric patients are strongly associated with genetic mutations and lead to pan-parenchymal disease refractory to medical and endoscopic treatment. Our aim was to assess pain resolution and glucose control in patients with CP and ARP following total pancreatectomy with islet auto-transplantation (TPIAT). METHODS: We retrospectively analyzed prospectively collected clinical data of 12 children who developed CP and ARP and underwent TPIAT when 21 years old or younger at the University of Chicago between December 2009 and June 2020. Patients with recurrent or persistent abdominal pain attributed to acute or chronic pancreatic inflammation and a history of medical interventions attempted for the relief of pancreatic pain were selected by a multi-disciplinary team for TPIAT. We followed patients post-operatively and reported data for pre-TPIAT, post-operative day 75, and yearly post-TPIAT. RESULTS: All 12 patients experienced complete resolution of pancreatic pain. The overall insulin-independence rate after 1 year was 66% (8/12) and 50% (3/6) at 4 years. Shorter duration of CP/ARP pre-TPIAT, higher mass of islets infused, and lower BMI, BMI percentile, and BSA were associated with insulin-independence post-TPIAT. CONCLUSIONS: TPIAT is a viable treatment option for pediatric patients with CP and ARP. Pediatric patients undergoing TPIAT for CP achieved resolution of pancreatic-type pain and reduced opioid requirements. The majority were able to achieve insulin-independence which was associated with lower pre-TPIAT BMI and higher islet mass transplanted (i.e., over 2000 IEQ/kg), the latter of which can be achieved by earlier TPIAT. LEVEL OF EVIDENCE: Treatment study, Level IV.

An Unusual Lung Mass of Heterotopic Pancreatic Tissue in a Neonate With an Elevated Immunoreactive Trypsinogen on Newborn Screen.

We present a case of a neonate with tracheoesophageal fistula and esophageal atresia along with a suspicious lung mass who had a false-positive newborn screen for cystic fibrosis due to an elevated serum immunoreactive trypsinogen with an additionally elevated serum lipase. The infant's lung mass was found to contain heterotopic pancreatic tissue consisting of acini, ducts, and islet cells, without an associated gastrointestinal duplication cyst. This constellation of congenital abnormalities has not been described in previous literature. Also, this is the first reported case of a neonate with elevated serum pancreatic enzymes in which the underlying etiology was discovered to be heterotopic pancreas.

Improving the potential for organ donation in an inner city Muslim American community: the impact of a religious educational intervention.

OBJECTIVE: We aimed to assess the willingness of Muslim Americans to be potential organ donors, to describe potential religious barriers to organ donation, and to evaluate the efficacy of a brief religious educational intervention. METHODS: Face-to-face survey with English-, Arabic-, and Urdu-speaking Muslim American adults in places of worship and gatherings. The two-part survey included questions about demographics and organ donation. A brief educational intervention followed, which included an explanation of organ donation, along with the evidence for Islam's support for organ donation. After this intervention, the questions about organ donation and brain death were repeated. RESULTS: The response rate was 81% (231 of 285). Fifty percent of the respondents would donate their organs. Twenty-five percent changed their opinion and accepted the idea of being donors after the educational intervention. Lack of awareness of the support of Islam to organ donation and fear of disfigurement were the most common barriers cited. CONCLUSION: Muslim Americans are less likely than Caucasian Americans to be organ donors, and the perceived lack of support from Islam for organ donation is a factor. The effectiveness of our brief religious education intervention suggests that further education may improve organ donation rates among the Muslim community.

Multiorgan Failure in a Malnourished Infant: Inappropriate Use of Goat Milk, Dilution, or Both?

Goat milk is gaining popularity in the United States as an alternative to cow and soy milk. The milk is presented as a healthier and less allergenic alternative, with casein and more MCT oil. The interest in goat milk has increased significantly with the recent formula shortage. Goat milk is available in many forms in the United States, including liquid and powdered formulations. However, there are no approved infant formulas in the United States that are goat milk-based. This case describes an infant who became critically ill due to family confusion over goat milk feeds, highlighting the importance of understanding the nutritional components and safety of various goat milk formulations.

Acute Recurrent Pancreatitis in a Child With INS-Related Monogenic Diabetes and a Heterozygous Pathogenic CFTR Mutation.

Given the close anatomical and physiological links between the exocrine and endocrine pancreas, diseases of 1 compartment often affect the other through mechanisms that remain poorly understood. Pancreatitis has been associated with both type 1 and type 2 diabetes, but its association with monogenic diabetes is unknown. Patients heterozygous for pathogenic CFTR variants are cystic fibrosis carriers and have been reported to have an increased risk of acute pancreatitis. We describe a 12-year-old patient with monogenic neonatal diabetes due to a pathogenic heterozygous paternally inherited mutation of the insulin gene (INS), c.94 G > A (p.Gly32Ser), who experienced 3 recurrent episodes of acute pancreatitis over 7 months in conjunction with poor glycemic control, despite extensive efforts to improve glycemic control in the past 4 years. Intriguingly, the maternal side of the family has an extensive history of adult-onset pancreatitis consistent with autosomal dominant inheritance and the proband is heterozygous for a maternally inherited, CFTR variant c.3909C > G (p.Asn1303Lys). Paternally inherited monogenic neonatal diabetes may have promoted earlier age-of-onset of pancreatitis in this pediatric patient compared to maternal relatives with adult-onset acute pancreatitis. Further study is needed to clarify how separate pathophysiologies associated with INS and CFTR mutations influence interactions between the endocrine and exocrine pancreas.

Preparedness of Residents to Manage Pediatric Nonalcoholic Fatty Liver Disease: A National Survey.

Objective: Non-Alcoholic Fatty Liver Disease (NAFLD) is reported to be the most common chronic pediatric liver disease. Little information is available on the adherence of residents in-training to the published guidelines for the evaluation and management of pediatric NAFLD.The goals of this study are: (i) to assess the consistency of screening and evaluation for NAFLD in obese and overweight children at continuity clinics by upper level residents, and (ii) to determine the residents' extent of training, knowledge, comfort and competence levels in NAFLD care. Methods: An electronic survey developed using REDCap was emailed to accredited Pediatric Residency Programs in the United States. Program directors and coordinators were requested to forward the survey to their upper level pediatric and medicine/pediatrics residents. Statistical analysis of responses (n= 399) was performed. Results: More than 88% of residents reported to be exposed to obese and overweight children, representing at least 25% of the patients encountered in clinics. Regardless of their training level, they inconsistently screened for (>60%), initiated evaluation of, or provided counseling on NAFLD in these patients, not following the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition guidelines. Over 80% of residents perceived to have received inadequate training resulting in insufficient knowledge on NAFLD, which they identified as their biggest barrier (25.7%). There was minimal statistically significant difference in the survey findings between training levels (PGY-2 vs PGY-3/4). Conclusions: Educational interventions should be implemented by pediatric residency programs to enhance educational core curricula for the early detection and initiation of management of NAFLD, an emerging public health problem.

Improved Kasai Hepatoportoenterostomy Outcomes After Implementation of a Dedicated Biliary Atresia Team.

It can be difficult or impractical to refer all biliary atresia (BA) patients to high-volume centers. Our hypothesis was that a low volume center could improve outcomes with implementation of a dedicated multidisciplinary BA team. We conducted a retrospective study of patients with BA who underwent hepatic portoenterostomy at our institution from 2003 to 2020, before and after the development of a dedicated BA team. Ten consecutive patients with BA were identified following the establishment of a dedicated BA team. Since the establishment of the BA team, total bilirubin (TB) clearance (TB < 2 mg/dL) achieved by 3 and 6 months has been 60% and 60%, respectively, and survival of the native liver (SNL) at 1 and 2 years post HPE at 90% and 86%, respectively. Outcomes were markedly improved after the team was established. A dedicated BA team prioritizing communication and expeditious workup can improve outcomes at a low volume center.

Unique hepatic manifestations of COVID-19-induced immune dysregulation in children.

The two cases we present are the first to demonstrate novel manifestations of COVID-19 related interaction between the liver and the immune system in pediatric patients. Written informed consent was obtained from the parent/guardian to publish this report in accordance with the journal's patient consent policy.

Use of shear wave elastography for the diagnosis and follow-up of biliary atresia: A meta-analysis.

BACKGROUND: Timely differentiation of biliary atresia (BA) from other infantile cholestatic diseases can impact patient outcomes. Additionally, non-invasive staging of fibrosis after Kasai hepatoportoenterostomy has not been widely standardized. Shear wave elastography is an ultrasound modality that detects changes in tissue stiffness. The authors propose that the utility of elastography in BA can be elucidated through meta-analysis of existing studies. AIM: To assess the utility of elastography in: (1) BA diagnosis, and (2) post-Kasai fibrosis surveillance. METHODS: A literature search identified articles that evaluated elastography for BA diagnosis and for post-Kasai follow-up. Twenty studies met criteria for meta-analysis: Eleven for diagnosis and nine for follow-up post-Kasai. Estimated diagnostic odds ratio (DOR), sensitivity, and specificity of elastography were calculated through a random-effects model using Meta-DiSc software. RESULTS: Mean liver stiffness in BA infants at diagnosis was significantly higher than in non-BA, with overall DOR 24.61, sensitivity 83%, and specificity 79%. Post-Kasai, mean liver stiffness was significantly higher in BA patients with varices than in patients without, with DOR 16.36, sensitivity 85%, and specificity 76%. Elastography differentiated stage F4 fibrosis from F0-F3 with DOR of 70.03, sensitivity 96%, and specificity 89%. Elastography also differentiated F3-F4 fibrosis from F0-F2 with DOR of 24.68, sensitivity 85%, and specificity 81%. CONCLUSION: Elastography has potential as a non-invasive modality for BA diagnosis and surveillance post-Kasai. This paper's limitations include inter-study method heterogeneity and small sample sizes. Future, standardized, multi-center studies are recommended.

Wilson's Disease: A Review for the General Pediatrician.

Wilson's disease, also known as hepatolenticular degeneration, is an autosomal recessive genetic disorder due to a mutation of the ATP7B gene resulting in impaired hepatic copper excretion and copper accumulation in various tissues. It is associated with the classic triad of cirrhosis, neurological manifestations, and the ocular finding of Kayser-Fleischer rings; however, the clinical presentation can vary greatly from incidental findings of abnormal liver enzymes to acute liver failure necessitating liver transplant. Pediatric patients may present with subtle findings including asymptomatic hepatomegaly, transaminitis, changes in behavior, movement disorders, or school failure. The general pediatrician may be the first to recognize these symptoms and should consider Wilson's disease in their differential diagnosis. Wilson's disease can be managed with lifelong chelation or zinc therapy in patients who present early in the disease; therefore, pediatricians should have a low threshold for referral to a pediatric hepatologist for further evaluation when it is suspected. [Pediatr Ann. 2018;47(11):e440-e444.].

Nutrition in Pediatric Chronic Liver Disease.

More than one-half of children with chronic liver disease suffer from malnutrition, which leads not only to a poor quality of life and even possibly catastrophic complications, but also to poor outcomes after a liver transplantation. These children have increased metabolic demands but often decreased intake with malabsorption and altered nutrient utilization, all of which make it difficult to keep up with nutritional demands. Assessment of a patient's nutritional status should be timely, and it should be performed routinely and proactively. When specific nutritional needs are identified, these should be addressed with a multidisciplinary team approach and with the close guidance of an experienced pediatric dietician. The assessment includes anthropometric and laboratory assessments, in addition to a careful physical examination and a detailed patient history. The specific nutritional needs vary, but generally dietary intervention focuses on increasing caloric intake, supplementation with medium-chain triglycerides, and prevention of essential fatty acid and fat-soluble vitamin deficiencies. [Pediatr Ann. 2018;47(11):e445-e451.].

Autoimmune Liver Diseases in Children.

Autoimmune liver disease remains difficult to diagnose, and distinguishing the various causes is difficult as well. In children, it can present with wide variation, including autoimmune hepatitis (AIH), primary sclerosing cholangitis (PSC), and the "overlap syndrome" of AIH/PSC, also known as autoimmune sclerosing cholangitis. These liver disorders are thought to be immune-mediated, but their etiology remains unclear. They are not secondary to inherited or acquired diseases and they are not associated with any drugs, so they can only be diagnosed if these other diseases or conditions are excluded. Because there is considerable commonality in the clinical presentation of these diseases but differences in their management, appropriate treatment may be delayed, increasing the risk for liver transplantation. Further education for general pediatricians and trainees is needed. This article reviews the differences between AIH and PSC, as well as the newly recognized overlap syndrome of both of these diseases. [Pediatr Ann. 2018;47(11):e452-e457.].

Hepatobiliary Manifestations in Systemic Disease.

Liver disease in children occurs via a multitude of primary illnesses such as autoimmune hepatopathy, biliary atresia, and nonalcoholic fatty liver disease. However, jaundice, hepatitis, and alterations in liver tests can often be a manifestation of systemic diseases. The liver is involved in many critical functions such as circulation, immunity, toxin clearance, and metabolism; when the heart, lungs, gastrointestinal tract, immune system, or endocrine systems are compromised, the liver will be affected. This article reviews common causes of liver injury as well as highlights key associations that should not be missed when diagnosing and managing children with liver disease. Becoming familiar with patterns of liver injury and arranging clues in the context of a thorough history and physical examination can help providers navigate the broad differential diagnosis of secondary liver disease. [Pediatr Ann. 2018;47(11):e458-e464.].

Cholestasis in Infancy.

Jaundice is a key manifestation of hepatobiliary disease in all age groups. Jaundice is a common finding in the first 2 weeks after birth, occurring in 2.4% to 15% of newborns. The neonatal liver is at increased susceptibility to cholestasis, with an incidence ranging from 1 in 2,500 to 1 in 5,000 live births. Etiologies vary, but the most common is biliary atresia. In 2004, the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition published guidelines for the evaluation of cholestasis that clearly stated any infant with jaundice persisting beyond age 2 weeks (3 weeks in breast-fed infants with an otherwise normal history and physical examination) should be evaluated with a fractionated serum bilirubin level. Prompt evaluation, diagnosis, and intervention are vital to optimize timely intervention and improve clinical outcomes. This article discusses the etiology, diagnosis and evaluation of cholestatis in infants. [Pediatr Ann. 2016;45(12):e414-e419.].