Medium-chain triglycerides and the impact on fat absorption, growth, nutritional status and clinical outcomes in children with cholestatic liver disease: A scoping review.

BACKGROUND & AIMS: Medium-chain triglyceride (MCT) supplementation is recommended in cholestatic liver disease, despite unclear evidence and no consensus on the ideal percentage of fat that should be MCT. The aim was to undertake a scoping review to identify the extent and type of evidence regarding how MCT supplementation, and percentage of MCT, affects fat absorption, growth, nutritional status and clinical outcomes (morbidity, mortality, transplant) in children with cholestatic liver disease. METHODS: Nine databases (MEDLINE, Embase, CINAHL, PubMed, AMED, Cochrane Library, Global Health, Scopus, Proquest) were searched from inception, with hand-searching conference abstracts and forward/backward citation searching. Eligible studies investigated oral/enteral MCT supplementation in children under 18y with cholestatic liver disease. There were no language limits. Two reviewers performed screening and data extraction independently. Data were synthesised narratively. RESULTS: Following title/abstract screening (1202 studies) and full-text review (40 studies), 24 studies were included comprising three small RCTs (n = 19 patients), one non-randomised controlled trial (n = 2), seven uncontrolled trials (n = 83) and thirteen case series/reports (n = 211). Seventeen studies were published before 1994. Outcomes included absorption, growth and nutritional status. MCT supplementation was associated with greater fat absorption (9/9 studies) and improved growth in some children (2/4). Higher percentage MCT was associated with greater magnesium and calcium absorption (1/1), essential fatty acid (EFA) deficiency (4/4), but not growth (3/3). CONCLUSIONS: The limited, mostly observational evidence from >30 years ago points to greater fat absorption on MCT and EFA deficiency on very high percentage MCT. High quality RCTs are required, particularly examining the impact of MCT at different percentages on growth, nutritional status and clinical outcomes.

Acute Hepatitis of Unknown Etiology Among Young Children: Research Agenda by the ESPGHAN Hepatology Committee.

In April 2022, an increased incidence of acute hepatitis cases of unknown etiology among previously healthy children across the United Kingdom was described. Since, more than 270 cases from the United Kingdom and hundreds more from all across the world have been reported. The majority of affected children were younger than 6 years of age. The clinical presentation was nonspecific with diarrhea and vomiting usually preceding the appearance of jaundice, abdominal pain, nausea, and malaise. Approximately 5% have required liver transplantation. An infectious etiology has been considered likely given the epidemiological and clinical features of the reported cases. Between 50 and 60% of the children tested were diagnosed with adenovirus infection although a clear etiological connection has still to be demonstrated. No link with SARS-CoV-2 infection and COVID-19 vaccine was found. What is not clear to date is whether the high number of acute hepatitis cases reported is related to a true increase in incidence or heightened awareness following on from the initial reports from the United Kingdom. The Hepatology Committee of the European Society of Pediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) developed a paper on the current outbreak of acute hepatitis of unknown etiology recognizing its importance and the need of approaching the current situation with a scientifically rigorous approach. The aims of the article are to summarize the current knowledge and to identify the most pertinent issues regarding the diagnosis and management of this condition and the research questions raised.

Long-Term Growth in Children and Young People with Autoimmune Liver Disease Treated with Daily Steroids.

OBJECTIVES: We aimed to evaluate long-term growth in children and young people with autoimmune liver disease (AILD) treated with daily steroids. METHODS: This is a retrospective observational cohort study of patients diagnosed between 1992 and 2004 before the age of 16 years. Growth measurements (height, weight and body mass index (BMI)) converted to z-scores were recorded, at diagnosis, 1 and 5 years after commencing treatment and at age 18 years and analyzed together with demographics, disease and treatment related characteristics. RESULTS: Seventy-four patients (35 female) were started on treatment at median age of 12.85 (Inter quartile range (IQR) 9.44, 14.14) years for median duration of 12.07 (IQR 8.68, 13.97) years. At all time-points, the mean z-scores for weight, height and BMI were within the normal range, indicating normal nutritional status. There was no difference in change in z-score for weight, height and BMI from diagnosis until age 18 years when comparing gender (male vs female), ethnicity (Caucasian vs non-Caucasian), diagnosis (AIH vs ASC) and presence of IBD (n = 23). Change in z-score was lower for height and weight for the < 12 years group compared to the ≥12 years age group ( P < 0.05 and P < 0.05, respectively). In addition, change in height z-score correlated positively with age at start of steroid treatment (r = 0.321, P < 0.05) and negatively with duration of steroid treatment (r = -0.321, P < 0.05). CONCLUSIONS: Growth of patients with AILD on a daily maintenance dose of steroids remains stable and within normal range during long-term follow up. Small, daily doses are effective in maintaining disease control and minimize the need for high-dose steroid pulses during relapses.

Proceedings of ESPGHAN Monothematic Conference 2020: "Acute Liver Failure in Children": Diagnosis and Initial Management.

OBJECTIVES: The Hepatology Committee of the European Society for Pediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) aims to educate pediatric gastroenterologists, members of ESPGHAN and professionals from other specialties promoting an exchange of clinical expertise in the field of pediatric hepatology. Herewith we have concentrated on detailing the recent advances in acute liver failure in infants and children. METHODS: The 2020 ESPGHAN monothematic three-day conference on pediatric hepatology disease, entitled "acute liver failure" (ALF), was organized in Athens, Greece. ALF is a devastating disease with high mortality and most cases remain undiagnosed. As knowledge in diagnosis and treatment of ALF in infants and children has increased in the past decades, the objective was to update physicians in the field with the latest research and developments in early recognition, curative therapies and intensive care management, imaging techniques and treatment paradigms in these age groups. RESULTS: In the first session, the definition, epidemiology, various causes of ALF, in neonates and older children and recurrent ALF (RALF) were discussed. The second session was dedicated to new aspects of ALF management including hepatic encephalopathy (HE), coagulopathy, intensive care interventions, acute on chronic liver failure, and the role of imaging in treatment and prognosis. Oral presentations by experts in various fields are summarized highlighting key learning points. CONCLUSIONS: The current report summarizes the major learning points from this meeting. It also identifies areas where there is gap of knowledge, thereby identifying the research agenda for the near future.

Proceedings of the European Society for Pediatric Gastroenterology, Hepatology and Nutrition Monothematic Conference, 2020: "Acute Liver Failure in Children": Treatment and Directions for Future Research.

OBJECTIVES: The Hepatology Committee of the European Society for Pediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) aims to educate pediatric gastroenterologists, members of ESPGHAN and professionals from other specialties promoting an exchange of clinical expertise in the field of pediatric hepatology. METHODS: The 2020 single topic ESPGHAN monothematic 3-day conference on pediatric liver disease, was organized in Athens, Greece and was entitled " Acute Liver Failure" (ALF). ALF is a devastating disease with high mortality and in a considerable fraction of patients, the cause remains unresolved. As knowledge in diagnosis and treatment of ALF in infants and children has increased in the past decades, the objective was to update physicians in the field with developments in medical therapy and indications for liver transplantation (LT) and to identify areas for future research in clinical and neurocognitive outcomes in ALF. RESULTS: We recently reported the epidemiology, diagnosis, and initial intensive care management issues in separate manuscript. Herewith we report on the medical treatment, clinical lessons arising from pediatric studies, nutritional and renal replacement therapy (RRT), indications and contraindications for LT, neurocognitive outcomes, new techniques used as bridging to LT, and areas for future research. Oral presentations by experts in various fields are summarized highlighting key learning points. CONCLUSIONS: The current report summarizes the current insights in medical treatment of pediatric ALF and the directions for future research.

Fat-soluble vitamin assessment, deficiency and supplementation in infants with cholestasis.

BACKGROUND: Infants with cholestasis are at risk of fat-soluble vitamin deficiency. The present study amied to review practice relating to the assessment, deficiency and supplementation of fat-soluble vitamins in infants with cholestasis. METHODS: The medical records of all newly diagnosed infants with cholestasis (conjugated bilirubin >17 mmol L-1 />20% total bilirubin) at King's College Hospital between 2017 and 2019 were reviewed. Data extracted included bilirubin, serum vitamin concentrations (A, D, E), international normalised ratio and evidence of supplementation at initial assessment, as well as at 3 and 6 months. Rates of vitamin assessment, deficiency and supplementation were compared using chi-squared or Fisher's exact test. RESULTS: In total, 136 infants (87 male) with idiopathic neonatal cholestasis (n = 62), biliary atresia (n = 40) and other aetiology (n = 34) were included. Assessment of serum vitamins (A, D, E) was low (33.3%-52.2%) and deficiency was initially high for vitamin D (60.6%) and vitamin E (70.9%). Supplementation prevalence at initial assessment was high (A, E, K), but dropped significantly at 3 and 6 months for vitamin E (p = 0.003) and vitamin K (p = 0.001), whereas vitamin D supplementation was consistently low throughout (25%-33.3%). Infants with biliary atresia were more likely to have vitamins assessed (3 months), be deficient initially (D, E) and supplemented (E, K) throughout. Supplementation continued in up to 80% of infants despite cholestasis resolving. CONCLUSIONS: Supplementation was generally high and continued in many despite cholestasis resolving. Deficiency of vitamin D and vitamin E was high at initial assessment, although lower at follow-up. Actual prevalence of deficiency of all vitamins is unknown because monitoring was not consistently performed.

Factors Impacting on Eating in Pediatric Intestinal-Transplant Recipients: A Mixed-Methods Study.

BACKGROUND: No empirical data are found examining why eating may be difficult for some children and not others following intestinal transplant. This study aimed to describe the eating behaviors and nutrition intake of intestinal-transplant-recipient children and examine factors that may impact on their eating. METHODS: Caregivers of all (n = 34) intestinal-transplant recipients <18 years of age in the United Kingdom were invited to participate in this mixed-methods study comprising questionnaires, a 3-day food diary and interviews. Questionnaires included the Children's Eating Behaviour Questionnaire and demographic/nutrition-related items. Analysis was by descriptive statistics using SPSS. Semistructured telephone interviews explored caregiver perceptions of their child's eating. Analysis was thematic. RESULTS: Nine caregivers were recruited and completed the questionnaire and food diary. Eight of these were interviewed. Home tube feeding was required by 77% (n = 7) of children post transplant, 56% (n = 5) were "food avoidant", and median energy intake was 93% (range, 61%-137%) of requirements. The findings revealed complex, interrelated positive and negative medical, caregiver, and child-related influences on eating. Learning to eat at the recommended age and having positive and significant pretransplant eating experiences appeared protective, whereas receiving nothing by mouth and having aversive experiences were barriers. CONCLUSION: This study provides the first empirical evidence of factors that may influence eating after intestinal transplant in children. The findings suggest promoting eating pretransplant, when the negative physical consequences can be managed, may be protective, and there may be eating-difficulty predictors that could be used to facilitate targeted interventions.