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Objective: Over the years, non-alcoholic fatty liver (NAFLD) disease has progressed to become the most frequent chronic liver disease in children and adolescents. The full pathology is not yet known, but disease progression leads to cirrhosis and hepatocellular carcinoma. Risk factors included hypercaloric diet, obesity, insulin resistance and genetics. Hyperglucagonemia appears to be a pathophysiological consequence of hepatic steatosis, thus, the hypothesis of the study is that hepatic fat accumulation leads to increased insulin resistance and impaired glucagon metabolism leading to hyperglucagonemia in pediatric NAFLD., Methods: 132 children and adolescents between 10 and 18 years, with varying degrees of obesity, were included in the study. Using Magnetic Resonance Imaging (MRI) average liver fat was determined, and patients were stratified as NAFLD (>5% liver fat content) and non-NAFLD (<5%). All patients underwent a standardized oral glucose tolerance test (OGTT). Additionally, anthropometric parameters (height, weight, BMI, waist circumference, hip circumference) such as lab data including lipid profile (triglycerides, HDL, LDL), liver function parameters (ALT, AST), uric acid, glucose metabolism (fasting insulin and glucagon, HbA1c, glucose 120 min) and indices evaluating insulin resistance (HIRI, SPISE, HOMA-IR, WBISI) were measured., Results: Children and adolescents with NAFLD had significantly higher fasting glucagon values compared to the non-NAFLD cohort (p=0.0079). In the NAFLD cohort univariate analysis of fasting glucagon was associated with BMI-SDS (p<0.01), visceral adipose tissue volume (VAT) (p<0.001), average liver fat content (p<0.001), fasting insulin concentration (p<0.001), triglycerides (p<0.001) and HDL (p=0.034). This correlation equally applied to all insulin indices HOMA-IR, WBISI, HIRI (all p<0.001) and SPISE (p<0.002). Multivariate analysis (R² adjusted 0.509) for the same subgroup identified HIRI (p=0.003) and VAT volume (p=0.017) as the best predictors for hyperglucagonemia. Average liver fat content is predictive in pediatric overweight and obesity but not NAFLD., Conclusions: Children and adolescents with NAFLD have significantly higher fasting plasma glucagon values, which were best predicted by hepatic insulin resistance and visceral adipose tissue, but not average liver fat content., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Maruszczak, Radzikowski, Schütz, Mangge, Bergsten, Forslund, Manell, Pixner, Ahlström, Kullberg, Mörwald and Weghuber.)

To compare patterns of sedentary (SED) time (more sedentary, SED + vs less sedentary, SED-), moderate to vigorous physical activity (MVPA) time (more active, MVPA + vs less active, MVPA-), and combinations of behaviors (SED-/MVPA + , SED-/MVPA-, SED + /MVPA + , SED + /MVPA-) regarding nonalcoholic fatty liver diseases (NAFLD) markers. This cross-sectional study included 134 subjects (13.4 ± 2.2 years, body mass index (BMI) 98.9 ± 0.7 percentile, 48.5% females) who underwent 24-h/7-day accelerometry, anthropometric, and biochemical markers (alanine aminotransferase (ALT) as first criterion, and aspartate aminotransferase (AST), gamma-glutamyl transpeptidase (GGT), AST/ALT ratio as secondary criteria). A subgroup of 39 patients underwent magnetic resonance imaging-liver fat content (MRI-LFC). Hepatic health was better in SED- (lower ALT, GGT, and MRI-LFC (p < 0.05), higher AST/ALT (p < 0.01)) vs SED + and in MVPA + (lower ALT (p < 0.05), higher AST/ALT (p < 0.01)) vs MVPA- groups after adjustment for age, gender, and Tanner stages. SED-/MVPA + group had the best hepatic health. SED-/MVPA- group had lower ALT and GGT and higher AST/ALT (p < 0.05) in comparison with SED + /MVPA + group independently of BMI. SED time was positively associated with biochemical (high ALT, low AST/ALT ratio) and imaging (high MRI-LFC) markers independently of MVPA. MVPA time was associated with biochemical markers (low ALT, high AST/ALT) but these associations were no longer significant after adjustment for SED time., Conclusion: Lower SED time is associated with better hepatic health independently of MVPA. Reducing SED time might be a first step in the management of pediatric obesity NAFLD when increasing MVPA is not possible., What Is Known: • MVPA and SED times are associated with cardiometabolic risks in youths with obesity. • The relationships between NAFLD markers and concomitant MVPA and SED times have not been studied in this population., What Is New: • Low SED time is associated with healthier liver enzyme profiles and LFC independent of MVPA. • While low SED/high MVPA is the more desirable pattern, low SED/low MVPA pattern would have healthier liver enzyme profile compared with high MVPA/high SED, independent of BMI, suggesting that reducing SED time irrespective of MVPA is needed to optimize liver health., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Nonalcoholic fatty liver disease (NAFLD) is the leading hepatic disease in children, ranging from steatosis to steatohepatitis and fibrosis. Age, sex, hormonal levels, pubertal stages, genetic risk- and epigenetic factors are among the many influencing factors. Appearing predominantly in children with obesity, but not exclusively, it is the liver's manifestation of the metabolic syndrome but can also exist as an isolated entity., Summary: Pediatric NAFLD differs from the adult phenotype. This narrative review on NAFLD in children with obesity provides an overview of the current knowledge on risk factors, screening, and diagnostic methods, as well state-of-the-art treatment. The recent discussion on the proposition of a new nomenclature - Metabolic [Dysfunction-] Associated Liver Disease - is featured, and current gaps of knowledge are discussed., Key Messages: Currently, there is no international consensus on screening and monitoring of pediatric NAFLD. With lifestyle interventions being the cornerstone of treatment, no registered pharmacological treatment for pediatric NAFLD is available. Development and validation of additional noninvasive biomarkers, scores and imaging tools suitable to subcategorize, screen and monitor pediatric patients are necessary. With a variety of upcoming and promising agents, clear recommendations for pediatric nonalcoholic steatohepatitis trials are urgently needed., (© 2021 S. Karger AG, Basel.)

Until recently, glucagon was considered a mere antagonist to insulin, protecting the body from hypoglycemia. This notion changed with the discovery of the liver-alpha cell axis (LACA) as a feedback loop. The LACA describes how glucagon secretion and pancreatic alpha cell proliferation are stimulated by circulating amino acids. Glucagon in turn leads to an upregulation of amino acid metabolism and ureagenesis in the liver. Several increasingly common diseases (e.g., non-alcoholic fatty liver disease, type 2 diabetes, obesity) disrupt this feedback loop. It is important for clinicians and researchers alike to understand the liver-alpha cell axis and the metabolic sequelae of these diseases. While most of previous studies have focused on fasting concentrations of glucagon and amino acids, there is limited knowledge of their dynamics after glucose administration. The authors of this systematic review applied PRISMA guidelines and conducted PubMed searches to provide results of 8078 articles (screened and if relevant, studied in full). This systematic review aims to provide better insight into the LACA and its mediators (amino acids and glucagon), focusing on the relationship between glucose and the LACA in adult and pediatric subjects. [ABSTRACT FROM AUTHOR]

Paediatric non-alcoholic fatty liver disease (NAFLD) has become the most common chronic liver disease in childhood. Obesity is the main risk factor. Nutrition and lifestyle are the key elements in preventing and treating NAFLD in the absence of approved drug therapy. Whilst recommendations and studies on macronutrients (carbohydrates, fat and protein) in adult NAFLD exist, the discussion of this topic in paediatric NAFLD remains contradictory. The purpose of this review is to provide state-of-the-art knowledge on the role of macronutrients in paediatric NAFLD regarding quality and quantity. PubMed was searched and original studies and review articles were included in this review. Fructose, sucrose, saturated fatty acids, trans-fatty acids and ω-6-fatty-acids are strongly associated with paediatric NAFLD. High consumption of fibre, diets with a low glycaemic index, mono-unsaturated-fatty-acids and ω-3-fatty-acids reduce the risk of childhood-onset NAFLD. Data regarding the role of dietary protein in NAFLD are contradictory. No single diet is superior in treating paediatric NAFLD, although the composition of macronutrients in the Mediterranean Diet appears beneficial. Moreover, the optimal proportions of total macronutrients in the diet of paediatric NAFLD patients are unknown. Maintaining a eucaloric diet and avoiding saturated fatty acids, simple sugars (mainly fructose) and a high-caloric Western Diet are supported by literature. [ABSTRACT FROM AUTHOR]