Pediatric Nonalcoholic Fatty Liver Disease Research Articles

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.

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 of obesity in children and adolescents. A non-invasive and reliable tool is needed to differentiate non-alcoholic steatohepatitis (NASH) from simple steatosis. This study evaluates 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 twenty one patients who were diagnosed with NAFLD by ultrasonography were included. They were categorized into 3 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 3 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

AbstractBackground/AimsNonalcoholic 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.MethodsA 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 χ2 test with Yates' correction and two‐sample t test.ResultsThe 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.ConclusionThis 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.

A serum-induced gene signature in hepatocytes is associated with pediatric nonalcoholic fatty liver disease.

Pediatric nonalcoholic fatty liver disease (NAFLD) is a growing problem, but its underlying mechanisms are poorly understood. We used transcriptomic reporter cell assays to investigate differences in transcriptional signatures induced in hepatocyte reporter cells by the sera of children with and without NAFLD. We studied serum samples from 45 children with NAFLD and 28 children without NAFLD. The sera were used to induce gene expression in cultured HepaRG cells and RNA-sequencing was used to determine gene expression. Computational techniques were used to compare gene expression patterns. Sera from children with NAFLD induced the expression of 195 genes that were significantly differentially expressed in hepatocytes compared to controls with obesity. NAFLD was associated with increased expression of genes promoting inflammation, collagen synthesis, and extracellular matrix remodeling. Additionally, there was lower expression of genes involved in endobiotic and xenobiotic metabolism, and downregulation of peroxisome function, oxidative phosphorylation, and xenobiotic, bile acid, and fatty acid metabolism. A 13-gene signature, including upregulation of TREM1 and MMP1 and downregulation of CYP2C9, was consistently associated with all diagnostic categories of pediatric NAFLD. The extracellular milieu of sera from children with NAFLD induced specific gene profiles distinguishable by a hepatocyte reporter system. Circulating factors may contribute to inflammation and extracellular matrix remodeling and impair xenobiotic and endobiotic metabolism in pediatric NAFLD.

Continuous age- and sex-specific reference ranges of liver enzymes in Chinese children and application in pediatric non-alcoholic fatty liver disease.

Alanine aminotransferase (ALT) is widely used to screen patients with hepatic diseases. However, the current reference ranges (< 50 U/L) were developed by laboratories and have not been validated in populations with a large number of healthy individuals. This study collected venous blood and anthropometric data from a total of 13,287 healthy children aged 3months to 18years who underwent routine physical examinations in the Department of Pediatric Healthcare. We applied the least mean square algorithm to establish age- and sex-related reference percentiles of serum levels of transaminases. For validation, we recruited 4276 children and adolescents with obesity/overweight who underwent evaluation and metabolic tests in the hospital. Using receiver operating characteristic curves, we determined age- and sex-specific upper limit percentiles of liver enzymes for fatty liver diseases. This study revealed a significant correlation between serum transaminase levels and age and sex (P < 0.01). These transaminase levels exhibited age- and sex-specific patterns. Among individuals in the non-alcoholic fatty liver disease (NAFLD) cohort, elevated ALT levels displayed a positive association with clinical markers of disease severity, including homeostatic model assessment of insulin resistance, waist-hip ratio, and serum uric acid levels (P < 0.01). According to the receiver operating characteristic curves, ALT levels at the 92.58th percentile for boys and the 92.07th percentile for girls yielded the highest accuracy and specificity. This study provides age- and sex-specific reference ranges for ALT, aspartate aminotransferase, and γ-glutamyltransferase in Chinese children and adolescents, making it the largest population study to date. Furthermore, the study establishes a precise upper limit for ALT levels, facilitating their use in NAFLD screening. Video Abstract.

Growth differentiation factor 15 performance as a novel non-invasive circulating biomarker of liver damage in paediatric non-alcoholic fatty liver disease

Growth differentiation factor 15 performance as a novel non-invasive circulating biomarker of liver damage in paediatric non-alcoholic fatty liver disease

Neutrophils: tissue and circulating signatures of pediatric non-alcoholic fatty liver disease.

The recent rise in non-alcoholic fatty liver disease (NAFLD) among children and adolescents led to a thorough investigation of the peculiarities of the cellular infiltrate which characterize the disease at young ages. This review aims to highlight the key involvement of neutrophils in the pathogenesis of pediatric NAFLD and the potential biomarker role of neutrophil-to-lymphocyte ratio (NLR) in the same pediatric disorder. Neutrophils, which are first responders to inflammation, constitute an abundant component of an infiltrate which is particularly disposed within the portal area of children with NAFLD. The involvement of neutrophils in triggering liver fibrosis has been related amongst others to reactive oxygen species (ROS) production, to the stimulation of hepatic stellate cells, and to their synthesis of neutrophil elastase. As immune imbalance characterizes NAFLD, potentially emerging non-invasive biomarkers such as NLR have been proposed for the detection and prognosis of NAFLD. In adults, several studies asserted the role of NLR in the prediction of advancing liver fibrosis and mortality in subjects with NAFLD. In children, data is scarce with contradicting findings, as some studies failed to identify significant shifting in NLR values in children with NAFLD when compared with obese controls without liver impairment. However, NLR seems to significantly increase in children with obesity and different degrees of NAFLD when compared to healthy counterparts and their changes seem to be reversible with weight loss. Still, paucity of pediatric studies calls for future research addressing the role of NLR in predicting NAFLD development and progression in children with obesity.

Association of chronic hepatitis B infection with hepatic steatosis and injury in nonalcoholic fatty liver disease children

BackgroundThe influence of chronic hepatitis B infection (CBI) on hepatic steatosis, necroinflammation, and fibrosis in nonalcoholic fatty liver disease (NAFLD) population was unclear. We aimed to investigate the effect of CBI on hepatic steatosis and assess the association between NAFLD co-existed CBI and hepatic injury in NAFLD pediatric population.MethodsConsecutive hospitalized children with biopsy-proven NAFLD with or without CBI were included. Hepatic steatosis, necroinflammation and fibrosis were evaluated by NASH CRN system and/or METAVIR scoring system, appropriately. Using multivariate logistic analysis, we identified variables associated with hepatic steatosis and liver injury.ResultsOf 223 biopsy-proven NAFLD children, 161 were NAFLD without CBI, and 62 were NAFLD co-existed CBI. Grouped by mild, moderate and severe hepatic steatosis, there was an inverse association between CBI and the severity of hepatic steatosis [odd ratio (OR) 0.037, 95% confidence interval (CI) 0.014–0.098]. In addition, we explored the relationship between CBI and hepatic necroinflammation and fibrosis in NAFLD children. Hepatic necroinflammation and fibrosis, respectively, were divided into two groups according to severity. And CBI was positively associated with hepatic necroinflammation (OR 6.125, 95%CI 1.958–19.158). However, there was no statistically independent association between CBI and significant hepatic fibrosis.ConclusionsCBI was inverse associated with the grade of steatosis and positively associated with severe hepatic necroinflammation, and does not appear to affect significant hepatic fibrosis in pediatric NAFLD children.

Clinical profile, referral trends, and real-world application of vibration-controlled transient elastography in children with non-alcoholic fatty liver disease in Singapore.

Pediatric non-alcoholic fatty liver disease (NAFLD) is a progressive disorder that is increasing in incidence globally. The study aims to describe the clinical profile and longitudinal outcome, including the utility of vibration-controlled transient elastography (VCTE), in children with NAFLD at a single tertiary liver unit in Singapore. Retrospective review of patients aged 0-18 years referred for NAFLD from 2003 to 2020 was conducted. Diagnosis was based on persistent elevation of alanine transaminase ≥2× the upper limit of normal in at-risk patients, and/or radiologic detection of hepatic steatosis, with the exclusion of other etiologies. VCTE-derived liver stiffness measurements (LSMs) ≤7.0 , 7.1-9.0, and ≥9.1 kPa were used to differentiate normal (F0-F1), significant fibrosis (F2), and advanced fibrosis (F3-F4), respectively. The study included 210 patients (72.4% male, mean age 11.6 years). New cases increased from 1.7/1000 referrals in 2003-2008 to 12.7 and 24.5/1000 referrals in 2009-2014 and 2015-2020, respectively. Significant proportion had dyslipidemia (41.4%), impaired glucose tolerance/diabetes (IGT/DM, 26.7%), and hypertension (17.1%). Only 6.2% had resolution of NAFLD after a mean follow-up of 3.7 years. Based on VCTE (n = 65), 41.5% had normal LSM, while 26.2% and 32.3% had increased likelihood of significant and advanced fibrosis, respectively. Age ≥16 years (odds ratio [OR] 8.9), IGT/DM (OR 6.5), and aspartate transaminase >70 U/L (OR 11.0) were independent risk factors associated with increased likelihood of advanced fibrosis. Incidence of pediatric NAFLD has increased dramatically in Singapore. Based on LSM estimation, pediatric NAFLD may be associated with an increased risk of developing advanced fibrosis by late adolescence.

Sex-specific differences in ectopic fat and metabolic characteristics of paediatric nonalcoholic fatty liver disease.

Sex-specific differences in obesity-related metabolic characteristics of non-alcoholic fatty liver disease (NAFLD) have rarely been explored, particularly in children with biopsy-verified NAFLD. The influence of sex hormones on ectopic fat disposition may cause inter-sex differences in various metabolic factors. This study aimed to assess the sex-based differences in ectopic fat and metabolic characteristics in children with NAFLD. We enrolled 63 children with biopsy-verified NAFLD (48 boys; mean age, 12.9 ± 3.2 years; mean body mass index z-score [BMI-z], 2.49 ± 1.21). Ectopic fat in the liver and pancreas was quantified based on magnetic resonance imaging within 2 days of the liver biopsy. Laboratory tests, body composition, blood pressure, and anthropometric measurements were also assessed. Sex-based differences were neither observed in age, BMI-z, or total body fat percentage nor in the proportions of obesity, abdominal obesity, diabetes, dyslipidaemia, hypertension, or metabolic syndrome. Furthermore, liver enzyme levels, lipid profiles, and pancreatic fat did not differ between the sexes. However, boys had significantly higher fasting insulin (median 133.2 vs. 97.8 pmol/L; p = 0.039), fasting plasma glucose (median 5.30 vs. 4.83 mmol/L; p = 0.013), homeostasis model assessment of insulin resistance (median 5.4 vs. 3.6; p = 0.025), serum uric acid (404.1 ± 101.2 vs. 322.4 ± 87.1 μmol/L; p = 0.009), and liver fat (median 26.3% vs. 16.3%; p = 0.014). Male-predominant hepatic steatosis and insulin resistance caused by sex-specific ectopic fat accumulation may contribute to higher uric acid levels in boys than in girls with NAFLD.

Decreased FXR Agonism in the Bile Acid Pool Is Associated with Impaired FXR Signaling in a Pig Model of Pediatric NAFLD.

The objective of this study was to investigate whether the impairment of farnesoid X receptor (FXR)-fibroblast growth factor 19 (FGF19) signaling in juvenile pigs with non-alcoholic fatty liver disease (NAFLD) is associated with changes in the composition of the enterohepatic bile acid pool. Eighteen 15-day-old Iberian pigs, pair-housed in pens, were allocated to receive either a control (CON) or high-fructose, high-fat (HFF) diet. Animals were euthanized in week 10, and liver, blood, and distal ileum (DI) samples were collected. HFF-fed pigs developed NAFLD and had decreased FGF19 expression in the DI and lower FGF19 levels in the blood. Compared with the CON, the HFF diet increased the total cholic acid (CA) and the CA to chenodeoxycholic acid (CDCA) ratio in the liver, DI, and blood. CA and CDCA levels in the DI were negatively and positively correlated with ileal FGF19 expression, respectively, and blood levels of FGF19 decreased with an increasing ileal CA to CDCA ratio. Compared with the CON, the HFF diet increased the gene expression of hepatic 12-alpha-hydrolase, which catalyzes the synthesis of CA in the liver. Since CA species are weaker FXR ligands than CDCA, our results suggest that impairment of FXR-FGF19 signaling in NAFLD pigs is associated with a decrease in FXR agonism in the bile acid pool.

Food Insecurity and Pediatric Nonalcoholic Fatty Liver Disease Severity

ObjectiveTo determine the association between food insecurity and pediatric nonalcoholic fatty liver disease (NAFLD). MethodsCross-sectional study of patients < 21 years of age with histologically confirmed NAFLD. The Household Food Security Survey Module was administered to determine food insecurity status. Skin lipidomics were performed to explore pathophysiologic mechanisms. ResultsSeventy-three patients with histologically confirmed NAFLD completed the Household Food Security Survey Module. Of these, the majority were male (81%) and non-Hispanic (53%), with a mean age at biopsy of 13±3 years. Food insecurity was seen in 42% (n=31). Comparison of features between food insecure and food secure subgroups revealed no differences in sex, ethnicity, BMI z-score, aminotransferases, or histologic severity. However, children experiencing food insecurity presented on average two years before their food secure counterparts (12.3 ± 3.0 vs. 14.4 ± 3.6 years, p = 0.015). A subset of 31 patients provided skin samples. Skin lipidomics revealed that food insecurity was associated with down-regulated features from the lipoamino acid class of lipids, previously linked to inflammation and adipocyte differentiation. ConclusionsFood insecurity is highly prevalent in children with NAFLD and is associated with earlier presentation. Lipidomic analyses suggest a possible pathophysiologic link that warrants further exploration.

Leukocyte cell-derived chemotaxin 2 correlates with pediatric non-alcoholic fatty liver disease.

Non-alcoholic fatty liver disease (NAFLD), newly renamed metabolic dysfunction-associated liver disease (MASLD), is a leading cause of liver disease in children and adults. There is a paucity of data surrounding potential biomarkers and therapeutic targets, especially in pediatric NAFLD. Leukocyte cell-derived chemotaxin 2 (LECT2) is a chemokine associated with both liver disease and skeletal muscle insulin resistance. Our aim was to determine associations between LECT2 and common clinical findings of NAFLD in pediatric patients. Enzyme-linked immunosorbent assay (ELISA) was used to measure serum LECT2 concentrations in children (aged 2-17 years) with and without NAFLD. LECT2 concentrations were then correlated to clinical parameters in NAFLD. Mean LECT2 was significantly elevated in children with NAFLD versus healthy controls (n = 63 vs. 42, 5.83 ± 1.98 vs. 4.02 ± 2.02 ng/mL, p < 0.005). Additionally, LECT2 had strong correlations with body mass index (BMI) (Pearson r = 0.301, p = 0.002). A LECT2 concentration of 3.76 mg/mL predicts NAFLD with a sensitivity of 90.5% and specificity of 54.8%. Principal component analysis and logistic regression models further confirmed associations between LECT2 and NAFLD status. This study demonstrates increased serum LECT2 concentrations in pediatric NAFLD, which correlates with BMI and shows strong predictive value within these patients. Our data indicate that LECT2 is a potential diagnostic biomarker of disease and should be further investigated in pediatric as well as adult NAFLD.

Development of Fibro-PeN, a clinical prediction model for moderate-to-severe fibrosis in children with nonalcoholic fatty liver disease.

Liver fibrosis is common in children with NAFLD and is an important determinant of outcomes. High-performing noninvasive models to assess fibrosis in children are needed. The objectives of this study were to evaluate the performance of existing pediatric and adult fibrosis prediction models and to develop a clinical prediction rule for identifying moderate-to-severe fibrosis in children with NAFLD. We enrolled children with biopsy-proven NAFLD in the Nonalcoholic Steatohepatitis Clinical Research Network within 90 days of liver biopsy. We staged liver fibrosis in consensus using the Nonalcoholic Steatohepatitis Clinical Research Network scoring system. We evaluated existing pediatric and adult models for fibrosis and developed a new pediatric model using the least absolute shrinkage and selection operator with linear and spline terms for discriminating moderate-to-severe fibrosis from none or mild fibrosis. The model was internally validated with 10-fold cross-validation. We evaluated 1055 children with NAFLD, of whom 26% had moderate-to-severe fibrosis. Existing models performed poorly in classifying fibrosis in children, with area under the receiver operator curves (AUC) ranging from 0.57 to 0.64. In contrast, our new model, fibrosis in pediatric NAFLD was derived from fourteen common clinical variables and had an AUC of 0.79 (95% CI: 0.77-0.81) with 72% sensitivity and 76% specificity for identifying moderate-to-severe fibrosis. Existing fibrosis prediction models have limited clinical utility in children with NAFLD. Fibrosis in pediatric NAFLD offers improved performance characteristics for risk stratification by identifying moderate-to-severe fibrosis in children with NAFLD.

THU146 Triglyceride Glucose Index Is Superior To The Homeostasis Model Assessment Of Insulin Resistance For Predicting Severity Of Nonalcoholic Fatty Liver Disease In Korean Children And Adolescents

Abstract Disclosure: J. Yoon: None. E. Kim: None. Background: Triglyceride glucose (TyG) index is known as a reliable insulin resistance surrogate marker to identify non-alcoholic fatty liver disease (NAFLD). Ultrasonographic fatty liver indicator (US-FLI) is proposed as a non-invasive, semi-quantitative method for predicting hepatitis in patients with NAFLD and accurately identifies histological severity. Few studies have compared the TyG index to homeostasis model assessment of insulin resistance (HOMA-IR) in the detection of NAFLD in children and adolescents. Additionally, there were no studies comparing the ability of TyG index and HOMA-IR to assess the severity of NAFLD. Objects: Therefore, we investigated the relationship between TyG index and NAFLD compared to HOMA-IR in identifying and assessing the severity of NAFLD in children and adolescents. Methods: Alanine aminotransferase (ALT) was used as the screening method for NAFLD (&amp;gt;26IU/L in boys and &amp;gt;22IU/L in girls), and US-FLI was performed on children who met these criteria. The US-FLI is a scoring system ranging 2-8 that evaluates based on intensity of liver/kidney contrast, posterior attenuation of ultrasound beam, vessel blurring, difficult visualization of gallbladder wall, difficult visualization of the diaphragm and areas of focal sparing. NAFLD is diagnosed by the minimum score ≥2. Healthy children of normal weight (body mass index 5-85th percentile) without metabolic comorbidities and no steatosis on ultrasound participated as a control group. TyG index was calculated as ln(fasting triglyceride (TG) [mg/dL] × fasting glucose [mg/dL]/2). Results: A total of 130 NAFLD patients (90 boys and 40 girls) included in this study, with mean age of 11.5±2.29 years. The control group consisted of a total of 28 subjects (17 boys and 11 girls) with mean age of 8.39±1.60 years. The US-FLI was significantly correlated with TyG index (r=0.264, p=0.003) but not with HOMA-IR after controlling for sex, age, and BMI. Multiple linear regression analysis showed that TyG index were significantly associated with US-FLI (β=0.202, p=0.002) not with HOMA-IR after controlling for sex, age, and BMI. The TyG index was superior to HOMA-IR in its ability to detect the severity of NAFLD in US-FLI ≥4, ≥5, and ≥6. Conclusions: Both TyG index and HOMA-IR were useful for detecting pediatric NAFLD. However, the TyG index was useful for detecting the severity of NAFLD, whereas HOMA-IR was not. Therefore, we propose to use the TyG index to predict and evaluate the severity of NAFLD in children. Presentation: Thursday, June 15, 2023

Association of single nucleotide polymorphism in patatin like phopholipase domain containing 3 (PNPLA3) gene with paediatric non-alcoholic fatty liver disease

Background: Non-alcoholic fatty liver disease (NAFLD) is the most unabating cause of chronic liver disease in children and adolescents. The aim of this study was to examine the association of paediatric NAFLD and single nucleotide polymorphism in patatin like phopholipase domain containing 3 (PNPLA3) gene. ­Methods:Τhis case-control study was carried out from June 2021 to December 2022. A total of 51 overweight children aged 6  17 years were recruited in this study and divided into NAFLD (cases) and non-NAFLD (controls) groups on the basis of hepatic steatosis detected by liver ultrasonography. We analyzed the rs738409 polymorphism by TaqMan assay and examined its association with NAFLD. ­­­­­Results:  A total of 31 (60.7%) children were in case group and 20 children were in control group. Body mass index, waist circumference, total cholesterol and triglycerides levels were statistically higher in NAFLD group. Homogygosity (GG status) and heterogygosity (CG status) for PNPLA3 polymorphism was seen in 2 (6.4%) and 18 (58.1%) children having NAFLD, respectively. PNPLA3 rs738409 genotypes were similar between case and control groups. Conclusion: No association was found between PNPLA3 rs 738409 SNP with the presence of NAFLD in children. Bangabandhu Sheikh Mujib Medical University Journal 2023;16(3): 139-143