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.

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.

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.

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.].

An Overview of Cirrhosis in Children.

Cirrhosis is the end result of nearly all forms of progressive liver disease. The diffuse hepatic process can be characterized as a state of inflammation progressing to fibrosis and resulting in nodular regeneration, ultimately leading to disorganized liver architecture and function. The underlying etiology of cirrhosis in children may often differ from adults owing to specific disease processes that manifest in childhood, including biliary atresia, galactosemia, and neonatal hepatitis. Although basic management strategies in children are similar to those in adults, the care given to children with cirrhosis must keep the child's growth and development of paramount importance. [Pediatr Ann. 2016;45(12):e427-e432.].

Pediatric Liver Transplantation: An Update for the Pediatrician.

Pediatric liver transplantation is a state-of-the-art treatment for children with end-stage liver disease. Over the past few decades, the advent of new surgical techniques using split liver grafts and living donors has drastically increased the organ availability for pediatric patients, while advances in immunosuppression have improved overall outcomes. The pediatrician is a key player in the multidisciplinary team that cares for these children starting with the timely referral of children who require liver transplantation to the active participation in optimizing the child's overall health before and after transplantation. [Pediatr Ann. 2016;45(12):e439-e445.].

Neonatal giant cell hepatitis: histological and etiological findings.

BACKGROUND: Neonatal giant cell hepatitis (NGCH) is an important diagnostic consideration in infants who present with jaundice. In this study, we examined 2 separate tertiary care center cohorts of individuals with NGCH to better understand the potential etiologies and their histological correlates. METHODS: All liver biopsies (1984 to 2007) with a histological diagnosis of NGCH were reviewed from 2 tertiary care centers. Cases diagnosed at the time of biopsy as biliary atresia, paucity of intrahepatic bile ducts, total parenteral nutrition associated liver injury, or α-1-antitrypsin deficiency were excluded. Liver biopsies were examined for cholestasis, giant cell change, extramedullary hematopoiesis, inflammation, and fibrosis. Follow-up clinical and laboratory findings were reviewed. RESULTS: Sixty-two cases of NGCH were identified (73% male) for analysis. The average age at liver biopsy was 2 months. Giant cell change affected on average 36% of hepatocytes (range, 5%-90%). Extramedullary hematopoiesis was common (74% of cases), often prominent, and included both myelopoiesis and erythropoiesis. Despite the term "hepatitis" in "neonatal giant cell hepatitis," portal and lobular inflammation was mild-to-absent in 95% of cases. Lobular cholestasis ranged from mild-to-moderate and demonstrated predominately a canalicular pattern (84% of cases). Bile ducts appeared hypoplastic (32% of cases) but were not absent or reduced in numbers. In contrast, another 18% of cases showed at least mild focal ductular proliferation. Portal or pericellular fibrosis was present in 30% of cases and was advanced in 8%. Subsequent clinical follow-up identified the following etiologies: Idiopathic (49%), hypopituitarism (16%), biliary atresia (8%), Alagille syndrome (6%), bile salt defects (6%), as well as several other entities present at 5% or less. Of note, the biopsy findings did not readily distinguish between the different etiologies with the exception that bile duct hypoplasia was more common in cases of hypopituitarism. CONCLUSIONS: In this series of cases, pan-hypopituitarism was the most common recognizable clinical association with neonatal giant cell hepatitis. However, most cases of neonatal giant cell hepatitis remain idiopathic and histological features do not readily distinguish among the various etiologies.