Screening for metabolic dysfunction-associated fatty liver disease: Time to discard the emperor's clothes of normal liver enzymes?
World journal of gastroenterology
Metabolic dysfunction-associated fatty liver disease (MAFLD) is the most prevalent chronic liver condition worldwide. Current liver enzyme-based screening methods have limitations that may missed diagnoses and treatment delays. Regarding Chen , the risk of developing MAFLD remains elevated even when alanine aminotransferase levels fall within the normal range. Therefore, there is an urgent need for advanced diagnostic techniques and updated algorithms to enhance the accuracy of MAFLD diagnosis and enable early intervention. This paper proposes two potential screening methods for identifying individuals who may be at risk of developing MAFLD: Lowering these thresholds and promoting the use of noninvasive liver fibrosis scores.
10.3748/wjg.v30.i22.2839
The accuracy of fatty liver index for the screening of overweight and obese children for non-alcoholic fatty liver disease in resource limited settings.
BMC pediatrics
BACKGROUND:Non-alcoholic fatty liver disease (NAFLD) has become the most common liver disease among children with a higher prevalence among obese. Fatty liver index (FLI), an algorithm derived to screen NAFLD using the waist circumference, body mass index, triglyceride and gamma glutamyl-transferase concentration was rarely investigated in Asian paediatric population. Since each component is routinely measured in clinical practice, it is feasible to measure FLI even in resource limited settings. Hence, we determined the accuracy of FLI for the screening of NAFLD in obese children in Southern Sri Lanka. METHODS:A descriptive cross sectional study was conducted on ninety five children (56 boys) aged 5-15 years with BMI ≥ 85th percentile for age and gender based on CDC 2000 growth charts recruited from the nutrition clinic at the Teaching Hospital, Karapitiya, Sri Lanka. NAFLD was diagnosed by ultrasonography. Factors associated with ultrasonographic fatty liver such as biochemical parameters and fatty liver index in either sex or the whole population were determined by a multivariate analysis. The ability of FLI to screen NAFLD was determined by the analysis of area under the receiver operator characteristic curve (AUROC) and the maximum Youden index analysis. RESULTS:Overweight and obese children with ultrasonographic fatty liver had a significantly higher FLI than those without fatty liver according to the multivariate analysis performed (Odds ratio 3.524; 95% CI 1.104-11.256, P = 0.033). AUROC of FLI for NAFLD was 0.692 (95% CI; 0.565-0.786) and the optimal cut off value for the screening of NAFLD was 30 (Maximum Youden index 0.2782, Sensitivity, 58.33%; Specificity, 69.49%). CONCLUSION:FLI could accurately be used in resource limited community settings and in epidemiological studies to screen overweight and obese children for NAFLD.
10.1186/s12887-022-03575-w
[Detecting non-alcoholic fatty liver in children with owerweight and obesity.]
García-López Nallely A,Jiménez-Álvarez Alicia,Murillo-Zamora Efrén
Revista medica del Instituto Mexicano del Seguro Social
Background:Non-alcoholic fatty liver disease (NAFLD) has serious health implications and upward trends of the disease, accompanied by the obesity epidemic worldwide. Objective:To screen for fatty liver in overweight and obese children and evaluate the factors associated with an increased likelihood of presenting a positive-screen result. Material and methods:In a cross-sectional study, 102 children were recruited at a secondary care medical unit. Serum alanine aminotransferase (ALT) levels were quantified and hepatic ultrasounds were performed; multiple logistic regression models were used to evaluate factors associated with the increased odds of presenting with NAFLD (fatty infiltration on ultrasound and ALT > 52 U/L for boys and > 44 U/L for girls). Results:The overall prevalence of NAFLD was 10.8%. In multivariate analysis, a waist-to-hip ratio ≥ 1 was associated with increased odds of screening positive for NAFLD (odds ratio (OR) = 4.96, 95% CI 1.17-20.90). Conclusions:Our findings indicate that one out of ten children with overweight or obesity has data suggestive of NAFLD and is at risk of presenting its consequences on health.
Risk stratification of adolescents for the screening of non-alcoholic fatty liver disease.
Pediatric obesity
BACKGROUND:Non-alcoholic fatty liver conditions in adolescence are associated with premature mortality in adulthood. Effective screening could impact the population burden of this disease. OBJECTIVES:We sought to determine which adolescents should be screened for non-alcoholic fatty liver using vibration-controlled transient elastography. METHODS:We simulated a non-alcoholic fatty liver screening program of 938 adolescents from the National Health and Nutritional Examination Survey of 2017/2018. We stratified subjects by body mass index and metabolic parameters and analyzed our data using standard diagnostic statistical measures. RESULTS:The weighted prevalence of non-alcoholic fatty liver and non-alcoholic fatty liver disease was 24.4%, and 3.8%, respectively. For all subjects with obesity (21.8% of the population), screening identified 61.8% of the non-alcoholic fatty liver cases. In a category of all subjects with obesity and overweight subjects with metabolic abnormalities (26.7% of the population), screening identified 71.2% of non-alcoholic fatty liver cases. CONCLUSIONS:The two groups most likely to benefit by transient elastography screening are adolescents with obesity and overweight adolescents with one metabolic abnormality. These criteria reduce the number of individuals to be tested by approximately 80% (from an approximate 32 million adolescents to 6-7.5 million adolescents), while retaining a diagnostic accuracy of 84%-85%.
10.1111/ijpo.12924
Τhe anthropometric and biochemical profile of pediatric non-alcoholic fatty liver disease: A systematic review and a meta-analysis.
Vadarlis Andreas,Chantavaridou Sofia,Kalopitas Georgios,Bakaloudi Dimitra Rafailia,Karanika Evangelia,Tsekitsidi Eirini,Chourdakis Michail
Clinical nutrition (Edinburgh, Scotland)
BACKGROUND & AIMS:Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease in children and one of the leading indications for liver transplantation in adults. However, current screening methods are inadequate and are accompanied by several disadvantages. This meta-analysis aims to identify the anthropometrical and biochemical characteristics most commonly appearing in pediatric NAFLD that could contribute to the diagnosis of the disease in the every-day clinical setting. METHODS:A systematic search was conducted in major electronic databases (MEDLINE, Scopus and Embase) up to 15th of August 2021. Primary outcome was the comparison of the anthropometric characteristics, whereas secondary outcomes were the comparisons of biochemical profile, lipid profile, and metabolic parameters in children with NAFLD compared with age-matched healthy controls. Quality assessment was performed with Newcastle-Ottawa Scale (NOS) and results were expressed as mean differences with 95% confidence intervals. RESULTS:Sixty-four studies were included. Two different comparisons were designed regarding the body mass status. Statistically significant differences were demonstrated by comparing children with NAFLD vs lean/normal weighted controls in body weight (23.0 kg, 95% CI: 14.0-31.8, P < 0.00001), height (3.07 cm, 95% CI: 0.21-5.94, P = 0.04), ΒΜΙ (10 kg/m, 95% CI: 8.36-11.7, P < 0.00001) and waist circumference 25.8 cm (95% CI: 20.6-30.9, P < 0.00001) and by comparing children with NAFLD vs overweight/obese controls in weight (6.81 kg, 95% CI: 3.81-9.81), height (3.18 cm, 95% CI: 1.24 to 5.13, P = 0.001), BMI (2.19 kg/m, 95% CI: 1.76-2.62, P < 0.00001) and WC (7.35 cm, 95% CI: 6.20-8.49, P < 0.00001). CONCLUSIONS:Anthropometrical and biochemical characteristics of children and adolescents with NAFLD are statistically significantly different compared to age-matched controls; these characteristics could be used to identify individuals at risk of developing NAFLD and related comorbidities.
10.1016/j.clnu.2021.11.016
Meta-analysis: global prevalence, trend and forecasting of non-alcoholic fatty liver disease in children and adolescents, 2000-2021.
Alimentary pharmacology & therapeutics
BACKGROUND:NAFLD is increasing in children. AIMS:To determine the recent trend and forecast the future global prevalence of paediatric NAFLD METHODS: We searched PubMed, Embase, Web of Science and Cochrane library databases from inception to 1 May 2021 for studies of children and adolescents (≤21 years) with NAFLD. Obesity was defined with weight at ≥95th percentile and overweight as 85th to <95th percentile as per the Center for Disease Control BMI-for-age percentile cut-offs. RESULTS:From 3350 titles and abstracts, we included 74 studies (276,091 participants) from 20 countries/regions. We included 14 studies in the general NAFLD prevalence analysis, yielding an overall prevalence of 7.40% (95% CI: 4.17-12.81) regardless of the diagnostic method, and 8.77% (95% CI: 3.86-18.72) by ultrasound. Among continents with more than one study, the prevalence of NAFLD was 8.53% (95% CI: 5.71-12.55) for North America, 7.01% (95% CI: 3.51-13.53) for Asia, and 1.65% (95% CI: 0.97-2.80) for Europe. NAFLD prevalence regardless of the diagnostic method was 52.49% (95% CI: 46.23-58.68, 9159 participants) and 39.17% (95% CI: 30.65-48.42, 5371 participants) among obese and overweight/obese participants, respectively. For the general population, trend analysis from 2000 to 2017 indicates an increasing global prevalence of paediatric NAFLD from 4.62% to 9.02% at a yearly increase of 0.26%, whereas forecast analysis predicts a prevalence of 30.7% by 2040. CONCLUSION:The prevalence of paediatric NAFLD varies by region and is 52.49% overall among the obese population and 7.40% in the general population. It is predicted to reach 30.7% by 2040.
10.1111/apt.17096
Comparison of diagnostic accuracy of screening tests ALT and ultrasound for pediatric non-alcoholic fatty liver disease.
Draijer Laura G,Feddouli Sana,Bohte Anneloes E,Vd Baan Slootweg Olga,Pels Rijcken Tammo H,Benninga Marc A,Stoker Jaap,Koot Bart G P
European journal of pediatrics
Alanine aminotransferase (ALT) and ultrasound (US) are the most commonly used tools for detecting non-alcoholic fatty liver disease (NAFLD). No direct comparison of these two modalities in children exists. We aimed to compare head-to-head the diagnostic accuracy of ALT and US and their combination for detecting NAFLD in children with obesity. Ninety-nine children with severe obesity underwent simultaneous serum-ALT and abdominal ultrasound (US steatosis score 0-3). Proton magnetic resonance spectroscopy was used as reference standard for detecting steatosis/NAFLD. ROC curve analyses were performed to determine diagnostic performance and to determine optimum screening cut-points aiming for a specificity ≥ 80%. The area under the ROC (AUROC) of ALT and US were not significantly different (0.74 and 0.70, respectively). At the optimal ALT threshold (≥40 IU/L), sensitivity was 44% and specificity was 89%. At the optimal US steatosis score (≥ 2), sensitivity was 51% and specificity was 80%. Combining ALT and US did not result in better accuracy than ALT or US alone.Conclusion: ALT and US have comparable and only moderate diagnostic accuracy for detecting hepatic steatosis in children with obesity. A stepwise screening strategy combining both methods does not improve diagnostic accuracy. What is Known: • Alanine aminotransferase (ALT) and ultrasound (US) are the most commonly used tools for detecting non-alcoholic fatty liver disease (NAFLD). • ALT and ultrasound have mediocre accuracy in detecting steatosis in children with obesity. What is New: • In a head-to-head comparison, the difference in diagnostic accuracy of ALT and ultrasound in detecting steatosis is not significant. • A stepwise screening strategy combining both methods does not improve diagnostic accuracy.
10.1007/s00431-019-03362-3
Postprandial triglycerides and fibroblast growth factor 19 as potential screening tools for paediatric non-alcoholic fatty liver disease.
Pediatric obesity
BACKGROUND:Better screening tools for paediatric NAFLD are needed. We tested the hypothesis that the postprandial triglyceride (TG) and fibroblast growth factor 19 (FGF19) response to an abbreviated fat tolerance test (AFTT) could differentiate adolescents with NAFLD from peers with obesity and normal weight. METHODS:Fifteen controls with normal weight (NW), 13 controls with obesity (OB) and 9 patients with NAFLD completed an AFTT. Following an overnight fast, participants consumed a high-fat meal. TG and FGF19 were measured at baseline and 4 h post-meal. Liver steatosis and fibrosis were measured via Fibroscan. RESULTS:Fasting TG and FGF19 did not differ among groups; 4 h TG in the NAFLD and OB groups were greater (197 ± 69 mg/dL; 157 ± 72 mg/dL, respectively) than NW (105 ± 45 mg/dL; p < 0.05) and did not differ from one another. Within the entire cohort, 4 h TG were stratified by high and low steatosis. Adolescents with high steatosis had 98% greater 4 h TG than adolescents with low steatosis. 4 h FGF19, but not fasting FGF19, was higher in children with low steatosis compared with high steatosis (p < 0.05). Using area under the receiver operating curve (AUROC), the only biochemical outcome with diagnostic accuracy for NAFLD was 4 h TG (0.77 [95% CI: 0.60-0.94; p = 0.02]). CONCLUSIONS:The postprandial TG response is increased in adolescents with obesity with hepatic steatosis, with or without NAFLD. Our preliminary analysis demonstrates 4 h TG differentiate patients with NAFLD from those without, supporting a role for the AFTT as a screening tool for paediatric NAFLD.
10.1111/ijpo.13007
Diagnostic accuracy of fibrosis tests in children with non-alcoholic fatty liver disease: A systematic review.
Draijer Laura G,van Oosterhout Janneke P M,Vali Yasaman,Zwetsloot Sabrina,van der Lee Johanna H,van Etten-Jamaludin Faridi S,Chegary Malika,Benninga Marc A,Koot Bart G P
Liver international : official journal of the International Association for the Study of the Liver
BACKGROUND & AIMS:Non-alcoholic fatty liver disease (NAFLD) has become the most common chronic liver disease in children. Even at young age, it can progress to liver fibrosis. Given the drawbacks of liver biopsy, there is a need for non-invasive methods to accurately stage liver fibrosis in this age group. In this systematic review, we evaluate the diagnostic accuracy of non-invasive methods for staging liver fibrosis in children with NAFLD. METHODS:We searched MEDLINE, Embase, Web of Science and the Cochrane Library, for studies that evaluated the performance of a blood-based biomarker, prediction score or imaging technique in staging liver fibrosis in children with NAFLD, using liver biopsy as the reference standard. RESULTS:Twenty studies with a total of 1787 NAFLD subjects were included, which evaluated three prediction scores, five simple biomarkers, two combined biomarkers and six imaging techniques. Most studies lacked validation. Substantial heterogeneity of studies and limited available study data precluded a meta-analysis of the few fibrosis tests evaluated in more than one study. The most consistent accuracy data were found for transient elastography by FibroScan®, ELF test and ultrasound elastography, with an area under the receiver operating characteristics curve varying between 0.92 and 1.00 for detecting significant fibrosis. CONCLUSION:Due to the lack of validation, the accuracy and clinical utility of non-invasive fibrosis tests in children with NAFLD remains uncertain. As studies have solely been performed in tertiary care settings, accuracy data cannot directly be translated to screening populations.
10.1111/liv.14908
Nonalcoholic Fatty Liver Disease in Children with Obesity: Narrative Review and Research Gaps.
Hormone research in paediatrics
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.
10.1159/000518595
Predictors of non-alcoholic fatty liver disease in children.
Pediatric research
OBJECTIVE:Abdominal obesity is strongly associated with the development of non-alcoholic fatty liver disease (NAFLD). Early identification and intervention may reduce the risk. We aim to improve pediatric NAFLD screening by comparing discriminative performance of six abdominal obesity indicators. METHODS:We measured anthropometric indicators (waist circumference [WC], waist-to-hip ratio [WHR], waist-to-height ratio [WHtR]), body composition indicators (trunk fat index [TFI], visceral fat area [VFA]), and endocrine indicator (visceral adiposity index [VAI]) among 1350 Chinese children aged 6-8 years. Using Spearman correlation, receiver operating characteristic (ROC) curves, and Logistic regression, we validated their ability to predict NAFLD. RESULTS:All six indicators can predict NAFLD robustly, with area under the curve (AUC) values ranged from 0.69 to 0.96. TFI, WC, and VFA rank in the top three for the discriminative performance. TFI was the best predictor with AUC values of 0.94 (0.92-0.97) and 0.96 (0.92-0.99), corresponding to cut-off values of 1.83 and 2.31 kg/m for boys and girls, respectively. Boys with higher TFI (aOR = 13.8), VFA (aOR = 11.1), WHtR (aOR = 3.1), or VAI (aOR = 2.8), and girls with higher TFI (aOR = 21.0) or VFA (aOR = 17.5), were more likely to have NAFLD. CONCLUSION:User-friendly body composition indicators like TFI can identify NAFLD and help prevent the progress of liver disease. TRIAL REGISTRATION:Chinese Clinical Trial Registry (ChiCTR) ( www.chictr.org.cn/enIndex.aspx , No. ChiCTR2100044027); retrospectively registered on 6 March 2021. IMPACT:Abdominal obesity increases the risk of pediatric non-alcoholic fatty liver disease (NAFLD). This study compared the discriminative performance of multiple abdominal obesity indicators measured by different methods in terms of accuracy and fastidious cut-off values through a population-based child cohort. Our results provided solid evidence of abdominal obesity indicators as an optimal screening tool for pediatric NAFLD, with area under the curve (AUC) values ranged from 0.69 to 0.96. User-friendly body composition indicators like TFI show a greater application potential in helping physicians perform easy, reliable, and interpretable weight management to prevent the progress of liver damage.
10.1038/s41390-021-01754-6
Ultrasound screening of paediatric non-alcoholic fatty liver disease (NAFLD): A critical literature review.
Radiography (London, England : 1995)
INTRODUCTION:Paediatric NAFLD is an increasing global health concern, which can be effectively managed with early detection. Screening, using accurate, affordable, and accessible tests is recommended, however, there is currently no consensus on the most appropriate tests. Although ultrasound techniques are widely used, their performance against reference tests have not been fully assessed. METHODS:A literature search of related databases for peer-reviewed original articles published from January 2010-March 2024 was conducted. Appropriate tools were used to systematise and document the search results and selected studies were quality assessed and critically appraised. Extracted data was subjected to thematic analysis and narrative synthesis. RESULTS:Eighteen articles met the inclusion criteria. B-mode and Quantitative ultrasound techniques were compared against MR spectroscopy, MRI-PDFF and Liver biopsy. CONCLUSION:Liver echogenicity and Steato-scores were the B-mode methods used. The former was less effective, with a maximum reported sensitivity of 70%. The latter reached up to 100% sensitivity, and >80% specificity. Ultrasound performed better with moderate-severe steatosis. There was not enough evidence to support steatosis grading, possibly due to small sample sizes and lack of established cut-off values. QUS (Quantitative Ultrasound)) methods including Continuous Attenuation Parameter (CAP), Attenuation Coefficient (AC), Ultrasound derived fat fraction (UDFF), Tissue Scatter Imaging (TSI) Hepato-Renal Index (HRI), Heterogeneity Index (HIA), Computer Assisted Ultrasound (CAUS) and Picture Archiving and Communication System (PACS-based Image analysis performed better than B-mode methods. Although QUS demonstrated excellent performance, with sensitivity and specificity of up to 100%, this will require further verification before implementation in practice. PRACTICE IMPLICATIONS:Ultrasound techniques can effectively be used for paediatric NAFLD screening, especially in higher-risk subjects. The steato-scores method is currently recommendable for this, with excellent potential for the use of QUS, after cut-off values and validation requirements have been addressed.
10.1016/j.radi.2024.07.006
Development and validation of a novel non-invasive test for diagnosing nonalcoholic fatty liver disease in Chinese children.
World journal of pediatrics : WJP
BACKGROUND:With the exploding prevalence of obesity, many children are at risk of developing nonalcoholic fatty liver disease. Using anthropometric and laboratory parameters, our study aimed to develop a model to quantitatively evaluate liver fat content (LFC) in children with obesity. METHODS:A well-characterized cohort of 181 children between 5 and 16 years of age were recruited to the study in the Endocrinology Department as the derivation cohort. The external validation cohort comprised 77 children. The assessment of liver fat content was performed using proton magnetic resonance spectroscopy. Anthropometry and laboratory metrics were measured in all subjects. B-ultrasound examination was carried out in the external validation cohort. The Kruskal-Wallis test, Spearman bivariate correlation analyses, univariable linear regressions and multivariable linear regression were used to build the optimal predictive model. RESULTS:The model was based on indicators including alanine aminotransferase, homeostasis model assessment of insulin resistance, triglycerides, waist circumference and Tanner stage. The adjusted R of the model was 0.589, which presented high sensitivity and specificity both in internal [sensitivity of 0.824, specificity of 0.900, area under curve (AUC) of 0.900 with a 95% confidence interval: 0.783-1.000] and external validation (sensitivity of 0.918 and specificity of 0.821, AUC of 0.901 with a 95% confidence interval: 0.818-0.984). CONCLUSIONS:Our model based on five clinical indicators was simple, non-invasive, and inexpensive; it had high sensitivity and specificity in predicting LFC in children. Thus, it may be useful for identifying children with obesity who are at risk for developing nonalcoholic fatty liver disease.
10.1007/s12519-023-00704-y
Screening for non-alcoholic fatty liver disease among obese and overweight children: Prevalence and predictors.
Indian journal of gastroenterology : official journal of the Indian Society of Gastroenterology
BACKGROUND:Non-alcoholic fatty liver disease (NAFLD) is increasingly recognized in obese and overweight children. NAFLD is the commonest cause of chronic liver disease in these children. We undertook a study to assess the prevalence of NAFLD and to identify the associated anthropometric and metabolic risk factors. METHODS:This cross-sectional study was done with 154 overweight and obese children. The study population was divided into 2 groups based on the presence or absence of NAFLD by screening with ultrasonography and/or alanine transaminase levels. Anthropometric (body mass index [BMI], waist circumference) and biochemical parameters (triglyceride, high density lipoprotein, low density lipoprotein, very low density lipoprotein, total cholesterol, insulin, homeostasis model assessment of insulin resistance [HOMA-IR], alanine transaminase, aspartate transaminase) were compared between these two groups. RESULTS:NAFLD was diagnosed based on abnormal screening in 79 (51.3%) overweight and obese children. No age or gender difference was noted between the 2 groups. There were no significant differences in BMI, systolic blood pressure, diastolic blood pressure, and waist circumference between patients with and without NAFLD. Low-density lipoprotein (LDL) cholesterol levels were found significantly higher in the NAFLD group. There was no significant difference in lipid profile apart from LDL cholesterol, aspartate transaminase, and HOMA-IR between the 2 groups. CONCLUSION:NAFLD is common in overweight and obese southern Indian children. High LDL cholesterol level is a risk factor for NAFLD in these children. Screening of this high-risk group for early diagnosis of NAFLD is essential to prevent and monitor further progression of the disease.
10.1007/s12664-021-01198-0
Diagnosis and Staging of Pediatric Non-Alcoholic Fatty Liver Disease: Is Classical Ultrasound the Answer?
Pediatric reports
The increased prevalence of non-alcoholic fatty liver disease (NAFLD) requires special attention in pediatric patients, as it manifests in them in a more severe and progressive way compared to adults. The implementation of the appropriate therapeutic interventions is determinant of the attempts to treat it. For that purpose, early diagnosis and staging of the disease is essential. The purpose of this review was to find and reveal the most appropriate diagnostic strategies and tools for diagnosis and staging of pediatric NAFLD/NASH based on their accuracy, safety and effectiveness. The methodology followed was that of the literature review. Particular emphasis was put on the recent bibliography. A comparative study of published articles about the diagnosis and management of pediatric NAFLD/NASH was also performed. In terms of diagnosis, the findings converged on the use of classical ultrasound. Ultrasound presented average sensitivity and specificity for diagnosing the disease in children, while in the adult population, sensitivity and specificity were significantly higher. Proton density fat fraction magnetic resonance imaging has been increasingly used for the diagnosis of steatosis in pediatric patients. Elastography is an effective tool for staging liver fibrosis and discriminating NASH from NAFLD in children. Even though liver biopsy is the gold standard, especially for NASH, it should be avoided for pediatric patients. Biochemical tests are less specific and less sensitive for the diagnosis of NAFLD, and some of them are of high cost. It seems that diagnostic imaging should be a first-line tool for the staging and monitoring pediatric NAFLD/NASH in order for appropriate interventions to be implanted in a timely way.
10.3390/pediatric13020039
Non-alcoholic Fatty Liver Disease in Children.
Current vascular pharmacology
Non-alcoholic fatty liver disease (NAFLD) has become the most common liver disease in the paediatric age. The growing prevalence of NAFLD and its advanced phenotype, non-alcoholic steatohepatitis (NASH), in children and adolescents parallels similar trends in obesity and type 2 diabetes mellitus. This trend may have serious long-term implications, including hepatic and extra-hepatic morbidity and mortality, the latter being related mostly due to cardiovascular disease and malignancies. This narrative review, which included 236 articles, summarizes current evidence on paediatric NAFLD, including pathophysiology, risk factors, complications, prevention and treatment (existing and emerging). Early recognition of NAFLD followed by timely and adequate management seems to be important on an individual basis. A global "call to action" regarding paediatric NAFLD seems appropriate to mitigate the burden of this disease.
10.2174/1570161121666221118155136
Non-alcoholic fatty liver disease and childhood obesity.
Shaunak Meera,Byrne Christopher D,Davis Nikki,Afolabi Paul,Faust Saul N,Davies Justin Huw
Archives of disease in childhood
Non-alcoholic fatty liver disease (NAFLD) in children and adolescents has an estimated prevalence of 36.1% in the context of obesity. This figure is anticipated to increase in conjunction with the global obesity epidemic. Worryingly, NAFLD in childhood persisting into adulthood is likely to be harmful, contributing to significant hepatic and extrahepatic morbidities. Early disease detection is required, although the optimum timing, frequency and mode of screening remains undetermined. While the efficacy of several medications, antioxidants, fatty acid supplements and probiotics has been investigated in children, healthy eating and physical activity remain the only prevention and treatment strategies for paediatric NAFLD. This short review discusses the epidemiology, diagnosis, pathogenesis and management of NAFLD in childhood obesity.
10.1136/archdischild-2019-318063
Nonalcoholic Fatty Liver Disease in Young Children with Obesity.
Childhood obesity (Print)
To evaluate the prevalence of suspected nonalcoholic fatty liver disease (NAFLD) in young children with obesity and determine associated risk factors. Retrospective single-center study of children with obesity, ages 2-6 years. Suspected NAFLD was defined as an alanine aminotransferase (ALT) >30 U/L. Multivariable analyses were performed to determine predictors of elevated ALT. Among 237 children 2-6 years old, 35% had elevated ALT. Multivariable analysis showed that higher BMI score [odds ratio (OR): 1.5 confidence interval (95% CI: 1.04-1.92)] and higher gamma-glutamyl transferase (GGT) [OR: 21.3 (95% CI: 3.7-121.1)] predicted elevated ALT. Of those with ≥2 ALT levels, 38% ( = 33/86) had a persistently elevated ALT (median ALT >30 U/L). Only 7% of patients with ALT >30 U/L underwent further testing to evaluate for alternative causes of liver disease. Suspected NAFLD is common in young children with obesity and predicted by obesity severity and GGT. Other cardiometabolic markers were equivalent between those with normal vs. elevated ALT, suggesting NAFLD onset may precede development of comorbidities. Earlier screening will enable prompt diagnosis and intervention, which may prevent or delay the onset of cardiometabolic diseases commonly associated with NAFLD in adolescence and adulthood.
10.1089/chi.2022.0048
Development of a prediction protocol for the screening of metabolic associated fatty liver disease in children with overweight or obesity.
Pediatric obesity
BACKGROUND:The early detection and management of children with metabolic associated fatty liver disease (MAFLD) is challenging. OBJECTIVE:To develop a non-invasive and accurate prediction protocol for the identification of MAFLD among children with overweight/obesity candidates to confirmatory diagnosis. METHODS:A total of 115 children aged 8-12 years with overweight/obesity, recruited at a primary care, were enrolled in this cross-sectional study. The external validation was performed using a cohort of children with overweight/obesity (N = 46) aged 8.5-14.0 years. MAFLD (≥5.5% hepatic fat) was diagnosed by magnetic resonance imaging (MRI). Fasting blood biochemical parameters were measured, and 25 candidates' single nucleotide polymorphisms (SNPs) were determined. Variables potentially associated with the presence of MAFLD were included in a multivariate logistic regression. RESULTS:Children with MAFLD (36%) showed higher plasma triglycerides (TG), insulin, homeostasis model assessment of insulin resistance (HOMA-IR), alanine aminotransferase (ALT), aspartate transaminase (AST), glutamyl-transferase (GGT) and ferritin (p < 0.05). The distribution of the risk-alleles of PPARGrs13081389, PPARGrs1801282, HFErs1800562 and PNLPLA3rs4823173 was significantly different between children with and without MAFLD (p < 0.05). Three biochemical- and/or SNPs-based predictive models were developed, showing strong discriminatory capacity (AUC-ROC: 0.708-0.888) but limited diagnostic performance (sensitivity 67%-82% and specificity 63%-69%). A prediction protocol with elevated sensitivity (72%) and specificity (84%) based on two consecutive steps was developed. The external validation showed similar results: sensitivity of 70% and specificity of 85%. CONCLUSIONS:The HEPAKID prediction protocol is an accurate, easy to implant, minimally invasive and low economic cost tool useful for the early identification and management of paediatric MAFLD in primary care.
10.1111/ijpo.12917
Childhood Obesity: A Risk Factor for Non-alcoholic Fatty Liver Disease in Adolescence.
Benítez Valeria Cuzmar,Alberti Gigliola,Uauy Ricardo,Pereira Ana,García Cristián,de Barbieri Florencia,Corvalán Camila,Santos José Luis,Mericq Verónica,Villarroel Luis,Gana Juan Cristóbal
Journal of pediatric gastroenterology and nutrition
Non-alcoholic fatty liver disease (NAFLD), defined as fat accumulation >5% in hepatocytes, may progress to fibrosis or cirrhosis later in life. NAFLD prevalence in adolescents has increased significantly in direct relation with obesity prevalence. Fatty liver has become the most frequent indication for liver transplantation in adults. OBJECTIVE:To identify anthropometric variables during the first 10 years of life associated to the risk of developing NAFLD in adolescence. METHODS:Longitudinal cohort study 'Growth and Obesity Chilean Cohort Study' (GOCS) consisting of 513 children born in 2002-2003, with yearly anthropometric data collected over a 10 year period. The presence of intra-hepatic fat in the livers of subjects 14-16 years of age was determined using abdominal ultrasound. In addition, elastography was performed on all participants with ultrasound evidence of NAFLD. RESULTS:9.7% of the participants presented findings compatible with NAFLD. After 2 years of age, obesity significantly and progressively increased the probability of NAFLD occurrence in adolescence. Obesity at 5 years of age was associated with the highest OR for NAFLD, reaching values of 8.91 (95% CI 3.03-16.11). Among participants with NAFLD, those with altered liver elasticity (≥7 Kpa) had greater weight, BMI z-score, waist and hip circumference and altered liver enzymes (p < 0.05). CONCLUSION:The risk of developing NAFLD in adolescence increases progressively with early obesity starting at age 2 years.
10.1097/MPG.0000000000002523
Evaluation of the feasibility of screening for paediatric non-alcoholic fatty liver disease.
Acta paediatrica (Oslo, Norway : 1992)
AIM:To evaluate the feasibility of screening for non-alcoholic fatty liver disease (NAFLD) in clinical practice and the acceptance of a screening strategy, and to identify factors that determine compliance. METHODS:A screening protocol, based on alanine aminotransferase measurement and introduced to healthcare workers of Dutch outpatient obesity clinics in 2017, was evaluated. Medical files of children who visited the largest outpatient obesity clinic between 2017 and 2020 were evaluated. Focus group discussions (FGDs) were conducted with 14 healthcare workers who had been using the screening protocol. RESULTS:Screening for NAFLD was performed in 477/571 (84%) of the children. Loss of follow-up was the major reason for inadequate screening. Follow-up was performed in 81/134 children with an abnormal screening result (61%). The FGDs indicated 13 barriers for screening, regarding guideline- and knowledge-related issues. CONCLUSION:Screening for NAFLD was performed in the vast majority of the children. However, adherence to the guideline after an abnormal initial screening result needs to be improved. This can be achieved by improving the loss of follow-up of patients' and physicians' awareness of the relevance of mildly elevated ALT levels.
10.1111/apa.16502