Pediatric Nonalcoholic Fatty Liver Disease Research Articles

Integrative Analyses of Genes of Pediatric Non-alcoholic Fatty Liver Disease Associated with Energy Metabolism.

Pediatric non-alcoholic fatty liver disease (NAFLD) is a chronic steatosis of the liver associated with energy metabolism in children and adolescents, failure to intervene promptly can elevate the risk of developing hepatocellular carcinoma. Therefore, this study aimed to understand the underlying mechanism of pediatric NAFLD and investigate potential biomarkers and therapeutic targets. We investigated genes using the GSE185051 data set related to energy metabolism from the GeneCards database, constructed protein-protein interaction network, identified hub genes and established networks representing interactions between these hub genes and miRNA, RNA-binding proteins, transcription factors, and drugs. Subsequently, we performed Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment analysis, Gene Set Enrichment Analysis (GSEA), and immune infiltration analysis. Our analysis identified 9 hub genes through the PPI network. The target molecules were identified through the interaction network between hub genes and miRNAs, RNA-binding proteins, transcription factors, and drugs. GO analysis revealed that hub genes were associated with oxidative stress responses and other pathways. KEGG analysis highlighted their involvement in pathways such as insulin resistance, among others. GSEA revealed that hub genes were highly enriched in pathways related to Omega-9 fatty acid synthesis, among others. Immune infiltration analysis suggested that mast cells and T follicular helper cells play significant roles in the pathogenesis of NAFLD. We identified the hub genes in pediatric NAFLD closely related to energy metabolism. These findings offer the potential for identifying potential novel diagnostic biomarkers, and establishing therapeutic targets for pediatric NAFLD.

Changes in intestinal flora associated with childhood sleep-disordered breathing and the pathogenesis of non-alcoholic fatty liver disease in children

Objective:To explore the interaction between pediatric sleep-disordered breathing（SDB）, the intestinal microbiota, and pediatric non-alcoholic fatty liver disease（NAFLD）. Methods:A total of 63 non-obese children（47 children with SDB in the experimental group and 16 without SDB in the control group） were enrolled in this study. The liver function and degree of SDB were assessed in both groups. High-throughput 16S rRNA sequencing was conducted to detect the composition and functional variations of the intestinal microbiota in the two groups of children. Results:Compared with children in the experimental group, serum ALT and AST levels were higher in the control group. and the relative proteobacteria abundance of intestinal flora increased, and the relative abundance of Bacteroidetes decreased significantly. Function including membrane transport, carbohydrate metabolism and lipid metabolism, were enriched in the intestinal microbiota of children with SDB. Conclusion:The composition and functional annotation of the pediatric liver functional status and gut microbiota were significantly different between the two groups of children with and without SDB. Changes in SDB-associated intestinal bacterial abundance may be related to the pathogenesis of pediatric NAFLD.

Liver magnetic resonance imaging, non-alcoholic fatty liver disease and metabolic syndrome risk in pre-pubertal Mexican boys.

Rising global pediatric obesity rates, increase non-alcoholic fatty liver disease (NAFLD) and metabolic syndrome (MetS) prevalence, with MetS being a NAFLD risk factor. NAFLD can be asymptomatic, with liver function tests insensitive to mild disease, and liver biopsy, risking complications. Thus, we investigated multiparametric MRI (mpMRI) metrics of liver fat (proton density fat fraction, PDFF) and disease activity (fibro-inflammation; iron-corrected T1, cT1), in a Hispanic pre-pubertal pediatric cohort, with increased risk of NAFLD. Pre-pubertal boys (n = 81) of varying Body-Mass Index (BMI) were recruited in Mexico City. Most children (81%) had normal liver transaminase levels, 38% had high BMI, and 14% had ≥ 3 MetS risk factors. Applying mpMRI thresholds, 12%, 7% and 4% of the cohort had NAFLD, NASH and high-risk NASH respectively. Participants with ≥ 3 MetS risk factors had higher cT1 (834ms vs. 737ms, p = 0.004) and PDFF (8.7% vs. 2.2%, p < 0.001) compared to those without risk factors. Those with elevated cT1 tended to have high BMI and high insulin (p = 0.005), HOMA-IR (p = 0.005) and leptin (p < 0.001). The significant association of increased risk of MetS with abnormal mpMRI, particularly cT1, proposes the potential of using mpMRI for routine pediatric NAFLD screening of high-risk (high BMI, high MetS risk score) populations.

Increased inter-atrial and intra-atrial conduction times in pediatric patients with non-alcoholic fatty liver disease.

The global incidence of pediatric non-alcoholic fatty liver disease (NAFLD) is rising, and it is linked to various potentially dangerous complications such as cardiovascular complications, particularly atrial fibrillation (AF). Atrial electromechanical conduction delay (EMD) has been reported as an early predictor for AF development. This study aimed to explore the link between NAFLD and the increased risk of AF development. This cross-sectional study was performed on 100 newly diagnosed NAFLD children (aged 14-18 years) as the patient group and 100 healthy individuals as a control group. Transthoracic echocardiography and simultaneous electrocardiography (ECG) recording were employed to estimate atrial electromechanical properties. EMD values were calculated for the inter-atrial, left intra-atrial, and right intra-atrial. Our results showed that pediatric patients with NAFLD exhibited significantly prolonged EMD values in the left and right intra-atrial as well as in inter-atrial regions compared to the control group (P = 0.03, P < 0.001, P < 0.01, respectively). Conclusion: Children with NAFLD show atrial electromechanical alterations that may presage AF in adulthood.

Cotinine exposure enhances the association of blood manganese and non-alcoholic fatty liver disease in American children: a cross-sectional study

This cross-sectional survey aims to determine whether cotinine exposure would enhance the relationship between blood manganese (Mn) and non-alcoholic fatty liver disease (NAFLD) in children using the NHANES database. Restricted cubic spline (RCS) and logistic regression analyses were adopted to determine the potential relationship. Besides, we tested the robustness of the results by performing trend tests and subgroup analyses. The study finally enrolled 866 children aged 18 years and below. Blood Mn was linearly linked to NAFLD and the risk of NAFLD was increased with the blood Mn elevation (P < 0.05). There was a notable relationship between blood Mn and NAFLD in crude model 1, which was still significant upon adjustment of all the identified covariates (all P < 0.05). Under Mn exposure, the cotinine-exposed group had a higher risk of NAFLD than the cotinine-unexposed group. In conclusion, blood Mn level is an independent risk factor for pediatric NAFLD, and cotinine exposure can enhance this relationship to some degree. Therefore, reducing cotinine exposure may alleviate detrimental consequences related to exposure to heavy metals in children.

Effect of Indo-Mediterranean diet versus calorie-restricted diet in children with non-alcoholic fatty liver disease: A pilot randomized control trial.

Dietary interventions and increased physical activity are the cornerstones for management of the paediatric non-alcoholic fatty liver disease (NAFLD). Though, no specific diet has been proven superior, Indo-Mediterranean diet (IMD) has shown promise in adult literature. Thus, we aimed to compare the effect of IMD and a standard calorie-restricted diet (CRD) in Indian overweight children and adolescents with biopsy-proven NAFLD. Thirty-nine consecutive biopsy-proven NAFLD children between the ages of 8 and 18 years were randomized into either IMD or CRD for 180 days, and various parameters were evaluated at baseline and then after 180 days (NCT05073588). A total of 34 subjects (18 in IMD and 16 in CRD group) completed the study. There was a significantly higher decrease in controlled attenuation parameter (CAP) values (as a marker of hepatic steatosis; on transient elastography) (95% CI: 4.2-73.4, p = 0.042), weight (95% CI: 0.75-5.5, p = 0.046) and body mass index (BMI) (95% CI: 0.21-2.05, p = 0.014) (but not in Pediatric NAFLD Fibrosis Index or PNFI; as a marker of hepatic fibrosis) in IMD group compared to the CRD group. Liver stiffness measurement, serum cholesterol and low-density lipoprotein levels and HOMA-IR decreased only in the IMD group (p < 0.001). Our statistical model showed that delta-Weight was the only independent variable associated with delta-CAP. Both IMD and CRD can improve the various anthropometric, clinical, imaging and biochemical parameters but IMD was superior to CRD in terms of reducing CAP values and weight/BMI over 180 days in overweight/obese NAFLD children.

Characterization of pediatric non-alcoholic fatty liver disease and prevalence and risk factors for small intestinal bacterial overgrowth in these children

Characterization of pediatric non-alcoholic fatty liver disease and prevalence and risk factors for small intestinal bacterial overgrowth in these children

Dynamic pattern of postprandial bile acids in paediatric non-alcoholic fatty liver disease.

Dysregulation of bile acids (BAs), as important signalling molecules in regulating lipid and glucose metabolism, contributes to the development of non-alcoholic fatty liver disease (NAFLD). However, static BA profiles during fasting may obscure certain pathogenetic aspects. In this study, we investigate the dynamic alterations of BAs in response to an oral glucose tolerance test (OGTT) among children with NAFLD. We recruited 230 subjects, including children with overweight/obesity, or complicated with NAFLD, and healthy controls. Serum BAs, 7-hydroxy-4-cholesten-3-one (C4) and fibroblast growth factor 19 (FGF19) were quantified during OGTT. Clinical markers related to liver function, lipid metabolism and glucose metabolism were assessed at baseline or during OGTT. Conjugated BAs increased while unconjugated ones decreased after glucose uptake. Most BAs were blunted in response to glucose in NAFLD (p > .05); only glycine and taurine-conjugated chenodeoxycholic acid (CDCA) and cholic acid (CA) were responsive (p < .05). Primary BAs were significantly increased while secondary BAs were decreased in NAFLD. C4 and FGF19 were significantly increased while their ratio FGF19/C4 ratio was decreased in NAFLD. The dynamic pattern of CDCA and taurine-conjugated hyocholic acid (THCA) species was closely correlated with glucose (correlation coefficient r = .175 and -.233, p < .05), insulin (r = .327 and -.236, p < .05) and c-peptide (r = .318 and -.238, p < .05). Among which, CDCA was positively associated with liver fat content in NAFLD (r = .438, p < .05). Additionally, glycochenodeoxycholic acid (GCDCA), CDCA and THCA were potential biomarkers to discriminate paediatric NAFLD from healthy controls and children with obesity. This study provides novel insights into the dynamics of BAs during OGTT in paediatric NAFLD. The observed variations in CDCA and HCA species were associated with liver dysfunction, dyslipidaemia and dysglycaemia, highlighting their potential roles as promising diagnostic and therapeutic targets in NAFLD.

Triglyceride-glucose-alanine aminotransferase index: A noninvasive serum predictor for identifying the severity of pediatric nonalcoholic fatty liver disease.

We hypothesized that the triglyceride-glucose (TyG)-alanine aminotransferase (ALT) index, which combines the TyG index with ALT, may enhance sensitivity and specificity in detecting the severity of nonalcoholic fatty liver disease (NAFLD). A total of 131 NAFLD patients with a mean age of 11.5 ± 2.29 years were enrolled, and severity was assessed by ultrasound fatty liver index (US-FLI) scoring. The TyG-ALT index was defined as ln(fasting triglyceride [mg/dL] × fasting glucose [mg/dL] × ALT [IU/L]/2). Multiple linear regression analysis revealed a significant association between the TyG-ALT index and US-FLI (β = 0.317, P < .001) after controlling for sex, age, and body mass index. The TyG-ALT index showed a more stable and superior ability to detect the severity of NAFLD compared to both ALT and the TyG index. The area under the curve values, listed in the order of ALT, TyG index, and TyG-ALT index, were as follows: 0.737 (P < .001), 0.599 (P = .055), and 0.704 (P < .001) at US-FLI ≥ 4 points; 0.717 (P < .001), 0.720 (P < .001), and 0.775 (P < .001) at US-FLI ≥ 5 points; and 0.689 (P < .05), 0.748 (P < .01), and 0.775 (P < .001) at US-FLI ≥ 6 points. The TyG-ALT index is associated with US-FLI score and superior to both ALT and the TyG index in predicting NAFLD severity. These findings indicate the potential of the TyG-ALT index in the management of pediatric NAFLD progression.

Diagnosis and treatment strategy of pediatric nonalcoholic fatty liver disease

Diagnosis and treatment strategy of pediatric nonalcoholic fatty liver disease

Survey of physicians' knowledge about pediatric nonalcoholic fatty liver disease in China.

To evaluate physicians' awareness and knowledge towards pediatric nonalcoholic fatty liver disease (NAFLD) and their attitude toward change in nomenclature from NAFLD to metabolic dysfunction-associated fatty liver disease (MAFLD) or metabolic dysfunction-associated steatotic liver disease (MASLD) in China. The questionnaire survey contained five parts (characteristics of the participants, epidemiology, diagnosis, management of NAFLD, and attitudes toward the nomenclature of MAFLD/MASLD). The participants included 53 hepatologists, 88 gastroenterologists (GEs), 74 endocrinologists (ENDOs), 61 primary care physicians (PCPs), and 157 pediatricians across 31 municipalities, provinces and autonomous regions of China's mainland. Hepatologists saw the largest number of pediatric NAFLD patients annually (median 9 [range 1-20]), with the lowest number by PCPs (even notwithstanding one patient annually). The primary sources of pediatric NAFLD knowledge were acquired via guidelines. Hepatologists had the highest total knowledge score among all five types of physicians. Approximately one-third of nonspecialists (ENDOs and PCPs) considered liver biopsy necessary for pediatric NAFLD patients, and this percentage increased to half in specialists (hepatologists and GEs). For nonspecialists, the major barriers to the management of pediatric NAFLD were poor patient adherence to lifestyle modifications and lacking confidence in managing NAFLD. Above 90% physicians agreed to change the nomenclature NAFLD to MAFLD; however, they were not sure whether it could reduce the economic burden. Despite the epidemic of pediatric NAFLD in China, a significant knowledge gap remains in the identification, diagnosis, and treatment of pediatric NAFLD, particularly among frontline workers such as pediatricians and PCPs. More education programs should be carried out in the future.

Prevalence of nonalcoholic fatty liver disease in pediatrics and adolescents: a systematic review and meta-analysis.

As childhood obesity escalates worldwide, the prevalence of nonalcoholic fatty liver disease (NAFLD) in pediatric and adolescent populations is also increasing. However, systematic studies and meta-analyses evaluating the prevalence of pediatric NAFLD remain limited. The MEDLINE, Korean Medical Database (KMBASE), Embase, Global Health, and Cochrane Library databases were searched from January 1997 to April 2023. Search terms included NAFLD or steatosis; nonalcoholic or steatohepatitis; child(ren), adolescent, or teenager; and prevalence, incidence, or epidemiology. A random-effects meta-analysis model was used to estimate the prevalence of pediatric NAFLD. A total of 2116 publications were found, of which 62 were included in the meta-analysis. Among them, 27 reported the prevalence in the general population and 39 in the obese population. The worldwide pooled prevalence of pediatric NAFLD was 13% [95% confidence interval (CI) 9-18%] in the general population and 47% (95% CI 41%-53%) in the obese population. Among 16 studies in the general population and 18 in the obese population, NAFLD prevalence varied by gender. In the general population, the prevalence of NAFLD was 15% (95% CI 8%-23%) in males and 10% (95% CI 6%-15%) in females. In the obese population, it was 54% (95% CI 46%-61%) in males and 39% (95% CI 30%-49%) in females. The global prevalence of pediatric NAFLD is rising in both the general and obese populations. Given the increasing rates of childhood obesity, epidemiological studies on the prevalence and incidence of NAFLD are needed.

Controlled attenuation parameter (CAP): the clinical value based on MRI-PDFF in children with obesity.

Controlled attenuation parameter (CAP) is a noninvasive and quantitative method to evaluate hepatic steatosis, which is not well evaluated in children. The aim ofthis study was to examine the diagnostic value of CAP forhepatic steatosis in children with obesity based on MR proton density fat fraction (PDFF). About 108 pediatric patients with nonalcoholic fatty liver disease (NAFLD) who were assessed for PDFF, CAP, and other laboratory results were enrolled. In this study, pediatric patients were separated for the obese group (n=80) and the severe obese group (n=28). Hepatic steatosis grades (0-3) were classified according to PDFF using cutoff values of 6.4 , 17.4, and 22.1 %. There are significant differences in CAP between the obese and severe obese groups (p<0.05). CAP showed a good correlation with PDFF in pediatric patients with NAFLDfor diagnosing hepatic steatosis using a cutoff valueof 265 dB/m (p<0.001). Meanwhile, ALT significantly outperforms CAP in receiver-operating curve (ROC) analysis for diagnosing hepatic steatosis grades. The diagnostic accuracy of CAP for steatosis is 77.8 %, and the diagnostic accuracy of ALT for steatosis is 83.3 %. While CAP holds promise as a diagnostic tool for pediatric NAFLD, its diagnostic performance warrants some caution. The potential of CAP is evident; however, ALTemerges as a simpler and more accurate measure for detecting hepatic steatosis in children. Further research is essential to determine the optimal role of CAP in pediatric NAFLD diagnosis and management.

Impact of Transgenerational Nutrition on Nonalcoholic Fatty Liver Disease Development: Interplay between Gut Microbiota, Epigenetics and Immunity.

Nonalcoholic fatty liver disease (NAFLD) has emerged as the most prevalent pediatric liver disorder, primarily attributed to dietary shifts in recent years. NAFLD is characterized by the accumulation of lipid species in hepatocytes, leading to liver inflammation that can progress to steatohepatitis, fibrosis, and cirrhosis. Risk factors contributing to NAFLD encompass genetic variations and metabolic disorders such as obesity, diabetes, and insulin resistance. Moreover, transgenerational influences, resulting in an imbalance of gut microbial composition, epigenetic modifications, and dysregulated hepatic immune responses in offspring, play a pivotal role in pediatric NAFLD development. Maternal nutrition shapes the profile of microbiota-derived metabolites in offspring, exerting significant influence on immune system regulation and the development of metabolic syndrome in offspring. In this review, we summarize recent evidence elucidating the intricate interplay between gut microbiota, epigenetics, and immunity in fetuses exposed to maternal nutrition, and its impact on the onset of NAFLD in offspring. Furthermore, potential therapeutic strategies targeting this network are also discussed.

Increased Farnesoid X Receptor agonism in frontal cortex is associated with neuronal loss in a pig model of pediatric non-alcoholic fatty liver disease

Clinical studies suggest a link between non-alcoholic fatty liver disease (NAFLD) and neurodegeneration, but the mechanisms connecting both pathologies remain unknown. Rodent models of liver failure have shown neurological decline to be associated with increased bile acid (BA) levels and BA-activated farnesoid X receptor (FXR) signaling in the brain, which may disrupt brain’s cholesterol metabolism and promote neuronal death. We have previously established a pediatric animal model of NAFLD by feeding juvenile Iberian pigs a diet high in fat and fructose (HFF) for 10 weeks. The aim of this study was to determine whether BAs and FXR gene expression were increased in the frontal cortex (FC) of NAFLD pigs, and whether these changes were associated with neuronal loss. Eighteen 15-day-old Iberian pigs were assigned to receive for 10 weeks either a control (CON) or a HFF diet. FC was collected for immunohistochemistry, metabolomics, and transcriptomics analyses. Functional enrichment analyses were performed on differentially expressed genes to identify Gene Ontology (GO) terms using the Database for Annotation, Visualization, and Integrated Discovery. All HFF-fed pigs developed NAFLD. Immunostaining of mature neurons with NeuN was lower in FC of HFF compared with CON (P ≤ 0.05), whereas total BA levels increased (P ≤ 0.05) in FC of HFF-fed pigs. Brain levels of cholic and conjugated deoxycholic acids, which are FXR agonists, increased ( P ≤ 0.05) in HFF compared with CON. Conversely, tauroursodeoxycholic acid, which has strong FXR-antagonistic effect and has been shown to exert neuroprotective functions, was decreased (P ≤ 0.001) in HFF and was positively correlated with NeuN staining intensity (R2 = 0.623; P ≤ 0.001). Expression of FC genes encoding FXR, BA synthetic enzymes sterol 24- and 27-hydroxylases, and BA transporters Na+-taurocholate cotransporting polypeptide, organic anion transporting polypeptide, and organic solute transporters alpha and beta did not differ between groups. GO terms associated with Wnt/β-catenin pathway, which promotes neuronal survival and neurogenesis, were downregulated in HFF-fed pigs ( P ≤ 0.05), whereas mitochondrial respiratory chain complex and mitochondrion increased in HFF compared with CON ( P ≤ 0.01). In conclusion, increased BA levels and FXR agonism in frontal cortex of NAFLD pigs was associated with dysregulated Wnt/β-catenin signaling pathway and neuronal loss. California State University Agriculture Research Institute (grants 58873 and 58913), California Polytechnic State University internal funding programs Baker/Koob, RSCA, Frost, BiOWiSH Technologies, Hilmar Ingredients, and Acorn Seekers. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Triglyceride Glucose Index is Associated with Ultrasonographic Fatty Liver Indicator in Children and Adolescents with Non-alcoholic Fatty Liver Disease

Non-alcoholic fatty liver disease (NAFLD) is defined as chronic hepatic steatosis and is becoming prevalent, along with the increasing trend for obesity in children and adolescents. A non-invasive and reliable tool is needed to differentiate non-alcoholic steatohepatitis from simple steatosis. This study evaluated the association between the triglyceride glucose (TyG) index and the ultrasonographic fatty liver indicator (US-FLI), and the possibility of using the TyG index for prediction of severity of pediatric NAFLD. One hundred and twenty one patients who were diagnosed with NAFLD by ultrasonography were included. They were categorized into three groups according to body mass index (BMI). Ninety-two were obese, and 19 and 10 were overweight and normal weight, respectively. The homeostatic model assessment for insulin resistance (HOMA-IR) was highest in the group with obesity (p=0.044). The TyG index and US-FLI did not differ significantly among the three BMI groups (p=0.186). Fourteen (11.6%) of the 121 patients had US-FLI ≥6, in whom the BMI-SDS and TyG index were higher (p=0.017, p=0.004), whereas HOMA-IR did not differ significantly from the group with US-FLI <6 (p=0.366). US-FLI was associated with BMI-SDS and the TyG index. TyG index was significantly associated with US-FLI after adjustment for BMI-SDS. The cut-off value for the TyG index for predicting US-FLI ≥6 was 8.91, with an area under the curve of 0.785. TyG index was associated with the degree of hepatic steatosis, suggesting that it might be a useful tool for predicting the severity of pediatric NAFLD.

The evaluation of non-alcoholic fatty liver disease in children with obesity with vibration-controlled transient elastography.

Parallel to the worldwide increase in obesity, the epidemic of chronic liver disease is increasing also in pediatric population. Our aim is to provide a different outlook on the current screening confusion in pediatric non-alcoholic fatty liver disease (NAFLD) with the non-invasive vibration-controlled transient elastography (VCTE) method. This single-center, cross-sectional, comparative study was performed at the tertiary center, included 95 patients with obesity and 116 controls, both groups were 9-18 years of ages. VCTE examinations performed in all patients. The cut-off values for controlled attenuation parameter (CAP) and liver stiffness measurement (LSM) were established by comparing the study and control groups. The cut-off for CAP was determined as >236 dB/m when comparing the two groups. The AUC was 0.900 (95% CI, 0.851-0.937) and the diagnostic accuracy was 77.9% and 91.4% for sensitivity and specificity, respectively. The cut-off value for LSM >5 kPa was determined by comparison of the two groups. The AUC was 0.794 (95% CI, 0.733-0.846) and the diagnostic accuracies were 50.5% and 90.5% for sensitivity and specificity, respectively. There is no benchmark method for screening pediatric NAFLD. However, VCTE is a promising method for screening pediatric NAFLD. It is accessible, repeatable and practical.

Patient perspective on exercise practices, preferences, and barriers in pediatric nonalcoholic fatty liver disease: A multicenter survey.

Nonalcoholic fatty liver disease (NAFLD) is prevalent among children, and lifestyle modification is the primary treatment approach. However, the optimal exercise duration, frequency, and intensity for managing NAFLD remain undefined. This study aimed to gain insights from the patient perspective by examining exercise behaviors, preferences, and barriers in children with NAFLD. A multicenter survey was conducted among children 8-18 years with NAFLD in pediatric gastroenterology clinics. Participants completed a questionnaire on exercise practices, preferences, and barriers, while parents completed a questionnaire on their willingness and ability to support their child's exercise. Data were analyzed using χ 2 test with Yates' correction and two-sample t test. The study included 408 children with NAFLD, with a mean age of 13.8 years. Approximately 52.5% of participants had physical education classes at school, while 59.5% engaged in extracurricular exercise, averaging 3.7 days per week. However, 11.5% reported no physical activity. A significant majority (81.1%) expressed interest in increasing their exercise levels, primarily driven by health-related factors. Time-related constraints were the most cited barriers to exercise (53.7%). Approximately 80% of parents demonstrated willingness and ability to support their child's exercise regimen. This study provides insights into exercise behaviors, preferences, and barriers among children with NAFLD. Half of the children lacked exercise opportunities at school but expressed interest in increasing their physical activity. Time limitation was the major obstacle cited. Parents are motivated to support increased physical activity. Exercise intervention programs for NAFLD should consider the perspective of the children and their families.

PARVB and HSD17B13 variants are associated with nonalcoholic fatty liver disease in children.

The aim of this study was to investigate the comprehensive genetic effects of exploratory variants of LYPLAL1, GCKR, HSD17B13, TRIB1, APOC3, MBOAT7, and PARVB on pediatric nonalcoholic fatty liver disease in addition to the previously reported variants of TM6SF2, PNPLA3, and SAMM50 in Korean children. A prospective case-control study was conducted involving 309 patients diagnosed using ultrasound and 339 controls. Anthropometric measurements, liver function tests, and metabolic marker analysis were conducted, and fibrosis scores were calculated. Transient elastography was performed in 69 some patients with nonalcoholic fatty liver disease. TaqMan allelic discrimination assays were used for genotyping. The genetic risk scores were calculated using significant variants, namely, HSD17B13, PARVB, PNPLA3, SAMM50, and TM6SF2, to evaluate the additive effect. Risk allele carriers of the PARVB variant showed significantly higher levels of aminotransferases, gamma-glutamyl transferase, alkaline phosphatase, pediatric nonalcoholic fatty liver disease fibrosis score, and aspartate aminotransferase/platelet ratio index. Individuals with a homozygous variant of HSD17B13 showed significantly lower levels of aminotransferase, gamma-glutamyl transferase, liver stiffness measurement, and aspartate aminotransferase/platelet ratio index than those with other genotypes. These parameters did not significantly differ among other variants of LYPLAL1, GCKR, TRIB1, APOC3, and MBOAT7. The genetic risk scores was identified as an independent risk factor for nonalcoholic fatty liver disease and had a positive association with severity. HSD17B13 has protective effects on the severity of pediatric nonalcoholic fatty liver disease. Variants of HSD17B13, PARVB, PNPLA3, SAMM50, and TM6SF2 had an additive effect on nonalcoholic fatty liver disease.

Breaking boundaries: Unraveling metabolic dysfunction-associated steatotic liver disease in children of India and Canada

Background: Non-alcoholic fatty liver disease (NAFLD) or metabolic dysfunction-associated steatotic liver disease (MASLD) is a major cause of chronic liver disease in children. Its prevalence is rising globally, yet it is uncertain if its onset and severity vary between countries. We aimed to compare pediatric NAFLD in two Canadian and Indian tertiary care centers. Methods: This study was conducted as a retrospective cohort study and patient related details were retrieved from the electronic records and reviewed. Results: The study analyzed a total of 184 children with NAFLD/MASLD (94 from the Indian site and 89 from the Canadian site) with concordance between NAFLD and MASLD definitions. The Indian children had a higher proportion of symptomatic presentations and family history of metabolic disorders ( p = 0.0001) while the Canadian children had higher median weight, BMI, blood pressure, and waist circumference ( p &lt; 0.05). Indian children had higher hepatic transaminases and low density lipoprotein levels, while the Canadian site had higher serum insulin, blood glucose, homeostasis model assessment of insulin resistance, high density lipoprotein cholesterol levels, liver stiffness, and controlled attenuation parameter values ( p &lt; 0.05). Majority (78%) of the Canadian children who underwent liver biopsy had significant fibrosis (&gt;stage 2). In the overall cohort, waist circumference could be identified as an independent risk factor, irrespective of country of origin, predicting hepatic fibrosis. Conclusions: The study found significant differences between cohorts. Canadian children showed higher obesity grades and greater hepatic steatosis and fibrosis severity. To comprehend the underlying causes, future studies are imperative.