Clinically Actionable Hypercholesterolemia and Hypertriglyceridemia in Children with Nonalcoholic Fatty Liver Disease

OBJECTIVE: To determine the percentage of children with nonalcoholic fatty liver disease (NAFLD) in whom intervention for low-density lipoprotein cholesterol or triglycerides was indicated based on National Heart, Lung, and Blood Institute guidelines. STUDY DESIGN: This multicenter, longitudinal cohort study included children with NAFLD enrolled in the National Institute of Diabetes and Digestive and Kidney Diseases Nonalcoholic Steatohepatitis Clinical Research Network. Fasting lipid profiles were obtained at diagnosis. Standardized dietary recommendations were provided. After 1 year, lipid profiles were repeated and interpreted according to National Heart, Lung, and Blood Institute Expert Panel on Integrated Guidelines for Cardiovascular Health and Risk Reduction. Main outcomes were meeting criteria for clinically actionable dyslipidemia at baseline, and either achieving lipid goal at follow-up or meeting criteria for ongoing intervention. RESULTS: There were 585 participants, with a mean age of 12.8 years. The prevalence of children warranting intervention for low-density lipoprotein cholesterol at baseline was 14%. After 1 year of recommended dietary changes, 51% achieved goal low-density lipoprotein cholesterol, 27% qualified for enhanced dietary and lifestyle modifications, and 22% met criteria for pharmacologic intervention. Elevated triglycerides were more prevalent, with 51% meeting criteria for intervention. At 1 year, 25% achieved goal triglycerides with diet and lifestyle changes, 38% met criteria for advanced dietary modifications, and 37% qualified for antihyperlipidemic medications. CONCLUSIONS: More than one-half of children with NAFLD met intervention thresholds for dyslipidemia. Based on the burden of clinically relevant dyslipidemia, lipid screening in children with NAFLD is warranted. Clinicians caring for children with NAFLD should be familiar with lipid management

In Children with Nonalcoholic Fatty Liver Disease, Zone 1 Steatosis is Associated with Advanced Fibrosis

Background & Aims Focal zone 1 steatosis, although rare in adults with nonalcoholic fatty liver disease (NAFLD), does occur in children with NAFLD. We investigated whether focal zone 1 steatosis and focal zone 3 steatosis are distinct subphenotypes of pediatric NAFLD. We aimed to determine associations between the zonality of steatosis and demographic, clinical, and histologic features in children with NAFLD. Methods We performed a cross-sectional study of baseline data from 813 children (age <18 years; mean age, 12.8 ± 2.7 years). The subjects had biopsy-proven NAFLD and were enrolled in the Nonalcoholic Steatohepatitis Clinical Research Network. Liver histology was reviewed using the Nonalcoholic Steatohepatitis Clinical Research Network scoring system. Results Zone 1 steatosis was present in 18% of children with NAFLD (n = 146) and zone 3 steatosis was present in 32% (n = 244). Children with zone 1 steatosis were significantly younger (10 vs 14 years; P < .001) and a significantly higher proportion had any fibrosis (81% vs 51%; P < .001) or advanced fibrosis (13% vs 5%; P < .001) compared with children with zone 3 steatosis. In contrast, children with zone 3 steatosis were significantly more likely to have steatohepatitis (30% vs 6% in children with zone 1 steatosis; P < .001). Conclusions Children with zone 1 or zone 3 distribution of steatosis have an important subphenotype of pediatric NAFLD. Children with zone 1 steatosis are more likely to have advanced fibrosis and children with zone 3 steatosis are more likely to have steatohepatitis. To achieve a comprehensive understanding of pediatric NAFLD, studies of pathophysiology, natural history, and response to treatment should account for the zonality of steatosis

Beyond the Surface: Mapping DDE's Metabolic Footprint on Adolescent Obesity.

BackgroundBariatric surgery is an intervention for severe obesity, leading to significant weight loss and metabolic improvements. However, the release of lipophilic chemicals accumulated in adipose tissue during weight loss presents a unique clinical challenge and research opportunity. Dichlorodiphenyldichloroethylene (DDE) is a persistent organic pollutant increasingly recognized as obesogen, while the biological mechanisms through which DDE influences body mass index (BMI) and waist circumference remain underexplored.ObjectivesWe aimed to identify metabolic signatures mediating the association between DDE exposure and weight loss by plasma and adipose tissue metabolomics.MethodsWe conducted a longitudinal study involving 60 adolescents with severe obesity undergoing bariatric surgery. We quantified p,p'-DDE concentrations in visceral adipose tissue collected during surgery and analyzed metabolic profiles from both adipose tissues collected at surgery and plasma samples collected at surgery, 6 months, 1 year, and 3 years postoperatively, using gas/liquid chromatography and high-resolution mass spectrometry. We used meet-in-the-middle approach coupled with a series of metabolome-wide association analyses to identify overlapping metabolite associated with both DDE exposure and weight loss outcomes.ResultsOur findings revealed that DDE concentrations in visceral adipose tissue are associated with significant alterations in metabolites locally in adipose tissue pre-surgery and systemically in plasma post-surgery. Eight plasma metabolites were significantly associated with DDE exposure over time, while 27 were associated with BMI. Notably, methylbutyroylcarnitine was identified as a potential mediator, showing a positive association with both exposure and outcome. Eight adipose tissue metabolites were associated with both DDE and longitudinal changes in plasma metabolites, suggesting an indirect pathway linking DDE and weight changes.DiscussionThese findings enhance our understanding of DDE's obesogenic effect. The involved metabolic changes could attenuate the efficacy of bariatric surgery in achieving sustained weight loss, underscoring the importance of integrating environmental health considerations into clinical practice. https://doi.org/10.1289/EHP16341

Allergic proctocolitis refractory to maternal hypoallergenic diet in exclusively breast-fed infants: a clinical observation

<p>Abstract</p> <p>Background</p> <p>Allergic proctocolitis (APC) in exclusively breast-fed infants is caused by food proteins, deriving from maternal diet, transferred through lactation. In most cases a maternal cow milk-free diet leads to a prompt resolution of rectal bleeding, while in some patients a multiple food allergy can occur. The aim of this study was to assess whether the atopy patch test (APT) could be helpful to identify this subgroup of patients requiring to discontinue breast-feeding due to polisensitization. Additionally, we assessed the efficacy of an amino acid-based formula (AAF) when multiple food allergy is suspected. amino acid-based formula</p> <p>Methods</p> <p>We have prospectively enrolled 14 exclusively breast-fed infants with APC refractory to maternal allergen avoidance. The diagnosis was confirmed by endoscopy with biopsies. Skin prick tests and serum specific IgE for common foods, together with APTs for common foods plus breast milk, were performed. After a 1 month therapy of an AAF all patients underwent a follow-up rectosigmoidoscopy.</p> <p>Results</p> <p>Prick tests and serum specific IgE were negative. APTs were positive in 100% infants, with a multiple positivity in 50%. Sensitization was found for breast milk in 100%, cow's milk (50%), soy (28%), egg (21%), rice (14%), wheat (7%). Follow-up rectosigmoidoscopy confirmed the remission of APC in all infants.</p> <p>Conclusions</p> <p>These data suggest that APT might become a useful tool to identify subgroups of infants with multiple gastrointestinal food allergy involving a delayed immunogenic mechanism, with the aim to avoid unnecessary maternal dietary restrictions before discontinuing breast-feeding.</p

Identifying a Window of Vulnerability during Fetal Development in a Maternal Iron Restriction Model

It is well acknowledged from observations in humans that iron deficiency during pregnancy can be associated with a number of developmental problems in the newborn and developing child. Due to the obvious limitations of human studies, the stage during gestation at which maternal iron deficiency causes an apparent impairment in the offspring remains elusive. In order to begin to understand the time window(s) during pregnancy that is/are especially susceptible to suboptimal iron levels, which may result in negative effects on the development of the fetus, we developed a rat model in which we were able to manipulate and monitor the dietary iron intake during specific stages of pregnancy and analyzed the developing fetuses. We established four different dietary-feeding protocols that were designed to render the fetuses iron deficient at different gestational stages. Based on a functional analysis that employed Auditory Brainstem Response measurements, we found that maternal iron restriction initiated prior to conception and during the first trimester were associated with profound changes in the developing fetus compared to iron restriction initiated later in pregnancy. We also showed that the presence of iron deficiency anemia, low body weight, and changes in core body temperature were not defining factors in the establishment of neural impairment in the rodent offspring

Resolution of refractory iron deficiency anemia following sleeve gastrectomy in an adolescent with severe obesity

Current surgical options for the management of adolescent obesity include Roux-en-Y gastric bypass (RYGB) and vertical sleeve gastrectomy (VSG), with recent trends favoring VSG. While both operations result in similar weight reduction, baseline micronutrient status may influence the choice of the procedure in youth. We describe an adolescent with severe obesity, iron deficiency, poor iron absorption, and their impact on decision-making for surgical treatment of her severe obesity. We present a case of a 15-year-old female with a BMI of 50 kg/m2 who was referred for bariatric surgery requesting a RYGB. During her preoperative evaluation, mild iron deficiency anemia was identified after noting a low hemoglobin concentration and mean corpuscular volume. Endoscopic biopsy revealed mild chronic gastritis. Iron supplementation over a 9-month period did not improve her anemia preoperatively and an oral iron challenge demonstrated inadequate absorption. A VSG was recommended to reduce further nutritional risk. Four months following surgery, her anemia resolved, and iron indices normalized while on supplemental micronutrients. Weight loss and hematologic status remained stable over the ensuing eight years of follow-up. Given the risks of micronutrient deficiency following bariatric surgery, particularly RYGB, preoperative evaluation of iron status among patients with microcytic anemia and anticipated nutritional risks of available surgical procedures should influence decision-making during surgical management. Keywords: Bariatric surgery, Obesity, Laparoscopic sleeve gastrectomy, Vertical sleeve gastrectomy, Iron deficiency anemia, Adolescen