Prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD), previously known as nonalcoholic fatty liver disease (NAFLD), and its sequelae of more severe forms such as metabolic dysfunction-associated steatohepatitis (MASH) is rapidly increasing in children with the rise in obesity. Successful and sustainable treatments for MASLD are lacking in children. We determined the therapeutic effect of N-acetyl cysteine (NAC) on biomarkers of oxidative stress, inflammation and insulin resistance (IR), liver enzymes, liver fat fraction (LFF) and liver stiffness (LS) in children with obesity and biopsy-confirmed MASLD.

Thirteen children (n = 13; age: 13.6 ± 2.8 years; NAS score >2) underwent a double-blind, placebo-controlled trial of NAC (either 600 or 1200 mg NAC/day) or placebo for 16 weeks. Measurements included LFF (magnetic resonance imaging), LS (ultrasound elastography), and body composition. Erythrocyte glutathione (GSH), liver enzymes, insulin, glucose, adiponectin, high-sensitivity c-reactive protein (hs-CRP), and interleukin-6 (IL-6) were also measured. homeostasis model assessment for insulin resistance (HOMA-IR) was calculated.

Sixteen-week NAC treatment improved (baseline adjusted between-group p < .05 for all) markers of inflammation (IL-6 and hs-CRP), oxidative stress (GSH), and IR (HOMA-IR) and reduced liver enzymes, LFF and LS. Body weight and body composition did not show beneficial changes.

Sixteen-week NAC treatment was well tolerated in children with obesity and MASLD and led to improvements in oxidative stress, inflammation and IR and liver outcomes. The results from this pilot study support further investigation of NAC as a therapeutic agent in children with MASLD.

Nonalcoholic fatty liver disease (NAFLD) is characterized by excessive intracellular lipid accumulation, oxidative stress, and inflammation. Cinnamyl alcohol (CA), one of the cinnamon extracts, has been shown to exhibit anti-oxidative and anti-inflammatory activities. We proposed that CA was beneficial to NAFLD.

Serum cytokines and components of the lipid metabolism were determined in children with NAFLD against age-matched comparisons. A NAFLD mouse model was established by high fat and high carbohydrate (HFHC) diet in male C57BL/6 mouse pups, followed by administration of CA. The effects of CA on lipid metabolism, oxidative stress, and inflammation in hepatic tissues were assessed.

Abnormal lipid metabolism and inflammatory responses were observed in the children with NAFLD as compared with the controls. CA reduced the weight of obese mice without affecting food intake as well as alleviating liver injury caused by HFHC feeding. CA was found to mitigate dyslipidemia and reduce hepatic steatosis in HFHC-fed mice by down-regulating genes related to lipogenesis, including peroxisome proliferator-activated receptor gamma (PPARγ), sterol regulatory element-binding transcription factor-1c (SREBP-1c), and acetyl-CoA carboxylase 1 (ACC1). Additionally, CA treatment reversed HFHC-induced oxidative stress and inflammation, evidenced by the decreased liver reactive oxygen species (ROS), hepatic inflammatory cytokine levels, and F4/80-positive macrophage infiltration in HFHC diet mice. CA reduced the protein levels of pyrin domain-containing protein 3 (NLRP3), adapter protein apoptosis-associated speck-like protein (ASC), and caspase-1 in the liver tissues significantly.

CA alleviates HFHC-induced NAFLD in mice, which is associated with the amelioration in lipid metabolism, oxidative stress, and inflammation.

Liver fibrosis of different etiologies is a serious health problem worldwide. There is no effective therapy available for liver fibrosis except the removal of the underlying cause of injury or liver transplantation. Development of liver fibrosis is caused by fibrogenic myofibroblasts that are not present in the normal liver, but rather activate from liver resident mesenchymal cells in response to chronic toxic or cholestatic injury. Many studies indicate that liver fibrosis is reversible when the causative agent is removed. Regression of liver fibrosis is associated with the disappearance of activated myofibroblasts and resorption of the fibrous scar. In this review, we discuss the results of genetic tracing and cell fate mapping of hepatic stellate cells and portal fibroblasts, their specific characteristics, and potential phenotypes. We summarize research progress in the understanding of the molecular mechanisms underlying the development and reversibility of liver fibrosis, including activation, apoptosis, and inactivation of myofibroblasts.

While linked to obesity and associated with an increased cardiovascular morbidity, non-alcoholic fatty liver disease (NAFLD) is an often-asymptomatic cause of chronic liver disease in children. Early detection provides opportunity for interventions to curb progression. Childhood obesity is on the rise in low/middle-income countries, but cause-specific mortality data associated with liver disease are scanty. Establishing the prevalence of NAFLD in overweight and obese Kenyan children would guide in public health policies aimed at early screening and intervention.

To investigate prevalence of NAFLD in overweight and obese children aged 6-18 years using liver ultrasonography.

This was a cross-sectional survey. After obtaining informed consent, a questionnaire was administered, and blood pressure (BP) measured. Liver ultrasonography was performed to assess fatty changes. Categorical variables were analysed using frequency and percentages. χ² test and multiple logistic regression model were used to determine relationship between exposure and outcome variables.

Prevalence of NAFLD was 26.2% (27/103, 95% CI=18.0% to 35.8%). There was no association between sex and NAFLD (OR1.13, p=0.82; 95% CI=0.4 to 3.2). Obese children were four times more likely to have NAFLD compared with overweight children (OR=4.52, p=0.02; 95% CI=1.4 to 19.0). About 40.8% (n=41) had elevated BP, but there was no association with NAFLD (OR=2.06; p=0.27; 95% CI=0.6 to 7.6). Older children (13-18 years) were more likely to have NAFLD (OR 4.42; p=0.03; 95% CI=1.2 to 17.9).

Prevalence of NAFLD was high in overweight and obese school children in Nairobi. Further studies are needed to identify modifiable risk factors to arrest progression and prevent sequelae.

Nonalcoholic fatty liver disease (NAFLD) is the most common hepatic disorder, affecting 22-28% of the adult population and more than 50% of obese people all over the world. Modulation of the fatty acids in diet as a means of prevention against nonalcoholic fatty liver disease in animal models (NAFLD) remains unclear. The treatment of NAFLD has not been described in specific guidelines so far. Thus, the justification for the study is to check modifications in macronutrients composition, fatty acids, in particular, play a significant role in the treatment of NAFLD regardless of weight loss.

To investigate different vegetable oils in prevention and progression of NAFLD in animal models.

For the experiment were used fifty C57BL/6J mice male fed with high fat and fructose diet (HFD) to induce the NAFLD status and they received different commercial vegetable oils for 16 weeks to prevent steatosis. Liver steatosis and oxidative stress parameters were analyzed using biochemical and histological methods. Fatty acids profile in the oils and in the liver samples was obtained.

The high fat and fructose diet led to obesity and the vegetable oils offered were effective in maintaining body weight similar to the control group. At the end of the experiment (16 weeks), the HFHFr group had a greater body weight compared to control and treated groups (HFHFr: 44.20 ± 2.34 g/animal vs. control: 34.80 ± 3.45 g/animal; p < 0.001; HFHFr/OL: 35.40 ± 4.19 g/animal; HFHFr/C: 36.10 ± 3.92 g/animal; HFHFr/S: 36.25 ± 5.70 g/animal; p < 0.01). Furthermore, the HFD diet has caused an increase in total liver fat compared to control (p < 0.01). Among the treated groups, the animals receiving canola oil showed a reduction of hepatic and retroperitoneal fat (p < 0.05). These biochemical levels were positively correlated with the hepatic histology findings. Hepatic levels of omega-3 decreased in the olive oil and high fat diet groups compared to the control group, whereas these levels increased in the groups receiving canola and soybean oil compared to control and the high fat groups.

In conclusion, the commercial vegetable oils either contributed to the prevention or reduction of induced nonalcoholic fatty liver with high fat and fructose diet, especially canola oil.

Nonalcoholic fatty liver disease (NAFLD) is a growing health problem in the pediatric population, due to the constantly increasing percentage of children with obesity. The objective of the study was to assess the occurrence of NAFLD based on ultrasound (USG) analysis and the use of alanine aminotransferase (ALT) in children with overweight and obesity depending on glucose tolerance. Medical records of 228 consecutive patients aged 2-18 years with overweight and obesity were reviewed retrospectively. Based on the oral glucose tolerance test children were divided into groups according to the severity of carbohydrate metabolism disorders. ALT, lipid parameters and insulin sensitivity indices HOMA, Matsuda and Quicki were analyzed. NAFLD was diagnosed (based on the USG) in 51 patients (23.61%) - the incidence in the impaired glucose tolerance (IGT) and type 2 diabetes (T2DM) group was significantly higher when compared to ones without glucose intolerance. Because of extreme values of metabolic parameters in TDM2 children being outliers, they were not considered in the statistical analysis of the study. 22 (11.58%) patients had elevated ALT values, of which 12 (54.55%) had hepatic steatosis features on ultrasound. 72.73% (n=32) patients with fatty liver features on USG had ALT values considered normal with cut-off point 42 U/l accepted in this study. Almost every fourth obese child in the study group presents features of fatty liver in ultrasound examination. Although ultrasound is not recommended by North American Society For Pediatric Gastroenterology, Hepatology &Nutrition(NASPGHAN) for the diagnosis of NAFLD in children, it allows identifying a high percentage of children with features of fatty liver. This percentage increases significantly in children with glucose intolerance.

During the last two decades, nonalcoholic fatty liver disease (NAFLD) has emerged as the most common hepatic disease in pediatrics, mainly owing to the rising prevalence of pediatric obesity. Epidemiological studies have shown that the progressive increase in NAFLD prevalence is associated not only with obesity but also with changes in dietary habits experienced by all age groups, characterized by the increased intake of added sugars and certain fatty acids. In this review article, we focus on the effect of oxidized fatty acids deriving from linoleic acid and arachidonic acid on the pathogenesis and progression of NAFLD in youth.

The objective of this study was to investigate the effect of dietary fatty acid (FA) composition on bile acid (BA) metabolism in a pig model of NAFLD, by using a multiomics approach combined with histology and serum biochemistry. Thirty 20-day-old Iberian pigs pair-housed in pens were randomly assigned to receive 1 of 3 hypercaloric diets for 10 wk: 1) lard-enriched (LAR; n = 5 pens), 2) olive oil-enriched (OLI; n = 5), and 3) coconut oil-enriched (COC; n = 5). Animals were euthanized on week 10 after blood sampling, and liver, colon, and distal ileum (DI) were collected for histology, metabolomics, and transcriptomics. Data were analyzed by multivariate and univariate statistics. Compared with OLI and LAR, COC increased primary and secondary BAs in liver, plasma, and colon. In addition, both COC and OLI reduced circulating fibroblast growth factor 19, increased hepatic necrosis, composite lesion score, and liver enzymes in serum, and upregulated genes involved in hepatocyte proliferation and DNA repair. The severity of liver disease in COC and OLI pigs was associated with increased levels of phosphatidylcholines, medium-chain triacylglycerides, trimethylamine-N-oxide, and long-chain acylcarnitines in the liver, and the expression of profibrotic markers in DI, but not with changes in the composition or size of BA pool. In conclusion, our results indicate a role of dietary FAs in the regulation of BA metabolism and progression of NAFLD. Interventions that aim to modify the composition of dietary FAs, rather than to regulate BA metabolism or signaling, may be more effective in the treatment of NAFLD.NEW & NOTEWORTHY Bile acid homeostasis and signaling is disrupted in NAFLD and may play a central role in the development of the disease. However, there are no studies addressing the impact of diet on bile acid metabolism in patients with NAFLD. In juvenile Iberian pigs, we show that fatty acid composition in high-fat high-fructose diets affects BA levels in liver, plasma, and colon but these changes were not associated with the severity of the disease.

Nonalcoholic fatty liver disease (NAFLD) is the leading chronic liver disease in youth, yet little is known about the adolescent patient's experience with NAFLD, which is key for treatment engagement. We examined adolescents' experiences with NAFLD diagnosis, thoughts on how NAFLD affects their daily life, understanding and perceptions of diagnosis and treatment, and impressions of how to improve care.

Utilizing a mixed-method design, adolescents with NAFLD (N = 16; Mean age = 15.8 years; Mean BMI = 37 kg/m 2 ) participated in focus groups. To supplement qualitative data, adolescents and their caregiver completed measures assessing illness perceptions, adolescent quality of life, and eating/activity behaviors.

Focus group themes suggested reactions to diagnosis varied from unconcerned to anxious. NAFLD diagnosis occurred within the context of other psychological/medical concerns and was not perceived to affect most adolescents' daily lives. Although adolescents understood general contributors to NAFLD, comprehension of their diagnosis varied. Adolescents were more likely to make lifestyle changes when families were supportive, and they preferred tailored recommendations for health behavior change from the healthcare team. Notably, 62.5% of adolescents were more concerned about their weight than NAFLD. Almost half (43.8%) identified as food insecure.

Adolescents with NAFLD may benefit from personalized treatment. Care could be enhanced by ensuring comprehension of diagnosis, problem-solving personal, and family barriers and increasing family support. Harnessing adolescents' desire for weight loss may be a more salient driver for change in disease status. Interventions should also address systemic barriers such as food insecurity to ensure equitable care.

Nonalcoholic fatty liver disease (NAFLD) is the most common type of chronic liver disease in children. The mechanisms that drive NAFLD disease progression in this specific patient population remain poorly defined. In this study, we obtained liver biopsy samples from a multiethnic cohort of pediatric patients with NAFLD (n = 52, mean age = 13.6 years) and healthy liver controls (n = 5). We analyzed transcriptomic changes associated with NAFLD stages using high-throughput RNA sequencing. Unsupervised clustering as well as pairwise transcriptome comparison distinguished NAFLD from healthy livers. We identified perturbations in pathways including calcium and insulin/glucose signaling occurring early in NAFLD disease, before the presence of histopathologic evidence of advanced disease. Transcriptomic comparisons identified a 25-gene signature associated with the degree of liver fibrosis. We also identified expression of the insulin-like growth factor binding protein (IGFBP) gene family (1/2/3/7) as correlating with disease stages, and it has the potential to be used as a peripheral biomarker in NAFLD. Comparing our data set with publicly available adult and adolescent transcriptomic data, we identified similarities and differences in pathway enrichment and gene-expression profiles between adult and pediatric patients with NAFLD. Regulation of genes including interleukin-32, IGFBP1, IGFBP2, and IGFBP7 was consistently found in both NAFLD populations, whereas IGFBP3 was specific to pediatric NAFLD. Conclusion: This paper expands our knowledge on the molecular mechanisms underlying pediatric NAFLD. It identifies potential biomarkers and directs us toward new therapies in this population.

The prevalence of childhood obesity has been increasing worldwide. This may explain the emergence of nonalcoholic fatty liver as the leading cause of liver disease. Several previous studies have addressed the association between thyroid function and nonalcoholic fatty liver disease.

To study the impact of weight reduction through lifestyle modifications in adolescents with obesity.

A prospective cohort study was done on 61 adolescents with obesity. Patients were evaluated at the first visit by the full history, clinical examination, and investigations (thyroid profile, lipid profile, liver function tests, HbA1c, and liver ultrasonography) as basal information. The intervention program included a dietary program, increasing physical activity, and decreasing sedentary activity. A postintervention evaluation was done at the end of six months which included anthropometric measures, laboratory results, and ultrasonographic estimation.

It was shown that the mean BMI of the participants had significantly decreased after lifestyle modification from (32.05 ± 3.36 kg/m2) to (28.1 ± 2.77 kg/m2) (P < 0.001). It also showed that the percentage of studied adolescents with elevated TSH decreased from 47.5% to 19.7% after the weight reduction program. Improvement was also achieved in the lipid profile and liver functions. The percentage of studied adolescents with ultrasound appearance of NAFLD decreased from 31.1% to 26.2% after weight reduction.

Lifestyle modification positively influences the metabolic derangement in obesity without medical treatment. ΔTSH is a significant predictor of the change in BMI z-score. It is also possible that hepatic steatosis affects thyroid function rather than the other way around.

The prevalence of non-alcoholic fatty liver disease (NAFLD) is increasing worldwide. Perinatal development is a critical window for altered, lifelong health trajectory, and evidence supports the role of perinatal programming in chronic metabolic diseases. To examine the impact of diet and bisphenol A (BPA) on the developmental trajectory of NAFLD in offspring, we exposed dams from pre-gestation through lactation to a human-relevant dose of oral BPA coupled with intake of high fat Western or Mediterranean-style diets. We assessed hepatic steatosis by quantifying hepatic triglycerides (TGs) and metabolic health by measuring body weight, relative organ weights, and serum hormone levels in dams and offspring at postnatal day 10 (PND10) and 10-months of age. In dams, consumption of the Western or Mediterranean diet increased hepatic TGs 1.7-2.4-fold, independent of BPA intake. Among offspring, both perinatal diet and BPA exposure had a greater impact on metabolic outcomes than on hepatic steatosis. At PND10, serum leptin levels were elevated 2.6-4.8-fold in pups exposed to the Mediterranean diet, with a trend for sex-specific effects on body and organ weights. At 10-months, sex-specific increases in organ weight and hormone levels were observed in mice perinatally exposed to Western + BPA or Mediterranean + BPA. These findings suggest lifestage-specific interaction of perinatal exposures to experimental diets and BPA on offspring metabolic health without effects on NAFLD later in life. Importantly, alterations in dam phenotype by diet and BPA exposure appear to impact offspring health trajectory, emphasizing the need to define dam diet in assessing effects of environmental exposures on offspring health.

Non-alcoholic steatohepatitis (NASH) is becoming a global disease with significant associated comorbidities. To date, there are no commercialized drugs to treat NASH, outside of India; however, there is an abundance of new molecular entities which are in clinical development, some in phase III trials. Many of these trials have created an especially heavy demand for USA-based subjects. Hepatologists currently play a major role in the diagnosis, treatment and clinical-trial enrolment of patients with NASH. However, NASH has a strong metabolic component, with patients often carrying comorbid diseases, such as type 2 diabetes mellitus, obesity, hyperlipidaemia, hypothyroidism and sex steroid disorders. The primary care physician, internist and endocrinologist stand at a pivotal position in the NASH healthcare delivery system, as many of the diseases they commonly encounter are associated with a higher risk of developing NASH. Specialty society practice guidelines are evolving regarding the identification and care of patients with NASH. This review of the literature, and assessment of IQVIA's proprietary patient claims database of diagnosis codes, patient encounters and treatments, substantiates the importance of the primary care provider and endocrinologist in the clinical care and clinical research of patients with NASH.

Understanding the burden of NAFLD among adolescents and young adults has become increasingly relevant. Our aim was to estimate the prevalence of NAFLD among adolescents and young adults in the United States. Data were obtained from National Health and Nutrition Examination Survey from 2007-2016. Adolescents and young adults aged 12 to 29 years were included. NAFLD was determined by the U.S. Fatty Liver Index in the absence of secondary causes of liver disease, and the differences in prevalence trends were analyzed based on age, gender, and race. Complete data were available for 4,654 adolescents and young adults (mean age 21 years; 50.9% male; 56.8% White, 20.9% Hispanic, and 13.3% Black). The overall prevalence of NAFLD among adolescents and young adults was 18.5%, ranging from 13.2% among early and middle adolescents (12-17 years) to 18.7% among late adolescents and young adults (18-24 years), to 24.0% among older young adults (25-30 years) (trend P < 0.001). The prevalence of NAFLD was higher for boys than for girls (aged 12-17: 15.1% vs. 11.3%; aged 18-24: 21.1% vs. 16.2%; aged 25-30: 28.7% vs. 19.2%, all P < 0.030). Among all age groups, Hispanics had a higher prevalence of NAFLD than Whites and Blacks (pairwise P < 0.001). Over the study time period, the prevalence of NAFLD among early and middle adolescents and young adults did not change (trend P > 0.80). In contrast, NAFLD prevalence among late adolescents increased (trend P = 0.018). In fact, White and Hispanic late adolescents were the drivers behind this increase in the prevalence of NAFLD. Conclusion: These data indicate an increasing trend in NAFLD prevalence among 18-24-year-olds. These data have important public health and policy implications.

Given the worldwide increase prevalence of overweight, obesity, and nonalcoholic fatty liver disease (NAFLD), the objective of this study was to evaluate whether the triglycerides and glucose (TyG) index is associated with hepatic steatosis in children with overweight or obesity. Apparently healthy children aged 5‑17 years were included and allocated into the groups with and without hepatic steatosis. The TyG index was calculated as Ln [fasting triglycerides (mg/dL) × fasting glucose (mg/dL)]/2. Hepatic steatosis was diagnosed by ultrasonography. A total of 177 children, 66 (37.3%) girls and 111 (62.7%) boys, were included in the study. According to the hepatic ultrasonography, they were allocated into the groups with (n = 100) and without (n = 77) hepatic steatosis. The adjusted analysis by gender, body mass index, and waist circumference revealed that HDL-C (OR 0.96; 95% CI: 0.93-0.99), triglycerides (OR 1.005; 95% CI: 1.001-1.009), AST (OR 1.03; 95% CI: 1.008-1.07), ALT (OR 1.03; 95% CI: 1.01-1.05), and TyG index (OR 4.07; 95% CI: 1.26-13.15) remained associated with hepatic steatosis.Conclusion: Compared to other biochemical markers, the TyG index is highly associated with the presence of fatty liver in children with overweight and obesity. What is known: • The triglycerides and glucose (TyG) index is effective in predicting high risk for incident nonalcoholic fatty liver disease (NAFLD) in adults. What is new: • Compared to other biochemical markers, the TyG index is highly associated with the presence of fatty liver in children with overweight or obesity. • The triglycerides and glucose index may be a useful tool to detect children at high risk of fatty liver.

In adults with chronic liver diseases, ultrasound and magnetic resonance shear wave elastography (SWE) can replace liver biopsy in several clinical scenarios. Several guidelines on the use of ultrasound SWE for the adult population have been published. However, the number of publications in the pediatric population is limited, and available guidelines on SWE do not specifically address pediatric chronic liver diseases. In this article, we review the literature on the use of SWE for pediatric chronic liver diseases and provide expert opinion on how to use SWE, both ultrasound and magnetic resonance techniques, in the pediatric population.

Nonalcoholic fatty liver disease (NAFLD) has emerged globally and is associated with inflammatory signaling. The underlying mechanisms remain poorly delineated, although NAFLD has attracted considerable attention and been extensively investigated. Recent publications have determined that angiotensin II (Ang II) plays an important role in stimulating NAFLD progression by causing lipid metabolism disorder and insulin resistance through its main receptor, Ang II type 1 receptor (AT1R). Herein, we explored the effect of supplementary S-adenosylmethionine (SAM), which is the main biological methyl donor in mammalian cells, in regulating AT1R-associated protein (ATRAP), which is the negative regulator of AT1R. We found that SAM was depleted in NAFLD and that SAM supplementation ameliorated steatosis. In addition, in both high-fat diet-fed C57BL/6 rats and L02 cells treated with oleic acid (OA), ATRAP expression was downregulated at lower SAM concentrations. Mechanistically, we found that the subcellular localization of human antigen R (HuR) was determined by the SAM concentration due to protein methylation modification. Moreover, HuR was demonstrated to directly bind ATRAP mRNA and control its nucleocytoplasmic shuttling. Thus, SAM was suggested to upregulate ATRAP protein expression by maintaining the export of its mRNA from the nucleus. Taken together, our findings suggest that SAM can positively regulate ATRAP in NAFLD and may have various potential benefits for the treatment of NAFLD.

Transient elastography (TE) is a valuable tool in assessment of hepatic steatosis and fibrosis using liver stiffness measurement (LSM) and controlled attenuation parameter (CAP), respectively. Although widely used in adults, little is known about performance characteristics and reproducibility of TE (using Fibroscan device) in evaluation of pediatric nonalcoholic fatty liver disease (NAFLD).

We prospectively recruited children with NAFLD. Three consecutive Fibroscan examinations were performed during the same visit-twice by a single expert operator and once by a different novice operator. Intra and inter-operator agreement was calculated using concordance correlation coefficient (CCC). Failure was defined as inability to obtain 10 valid measurements and examination was considered unreliable if LSM interquartile range/median was greater 30%.

Fifty-one children (34 boys; median age 15 years) were recruited. Failure rates for expert and novice operator were 10% (5/51) and 12% (6/51) while unreliable readings were obtained in 2% (1/46) and 4% (2/45) of patients, respectively. Patients with failed/unreliable measurements were significantly more obese (median BMI 46.2 vs 33.1 kg/m2, P = 0.002) compared with those with reliable measurements. The intra-operator agreement was almost perfect for LSM and substantial for CAP values (CCC = 0.85 and 0.73, respectively). Inter-operator agreement was substantial for LSM and moderate for CAP values (CCC = 0.76 and 0.58, respectively). The inter-operator agreement in LSM did not vary significantly over time but showed an inverse correlation with BMI and CAP.

Our study demonstrated that use of TE in assessment of hepatic fibrosis and steatosis in children with NAFLD is highly reliable with low failure rate and highly reproducible with high intra- and inter-operator reproducibility.

Overweight might represent only the early stage of obesity or it might act as a trigger of self-awareness turning into an ideal chance for preventing further obesity development.The aim of this study was to assess the differences between overweight and obese children in terms of anthropometric, low-grade systemic inflammation, liver impairment and atherosclerotic risk.We performed a study on 132 children aged between 5 and 18 years, divided according to the BMI into 2 groups: group 1 to 76 obese children, and group 2 to 56 overweight children, assessing anthropometric, laboratory and elastography parameters.We obtained significantly higher values of anthropometric parameters in obese children versus overweight ones. We found higher levels of leukocytes, lymphocytes, AST, ALT, and E median (P = .0345, P = .0103, P < .0001, P = .0008 and P < .0001) in the obese group as compared to the overweight one. BMI was positively correlated with neutrophils, NLR, ESR, glycemia, anthropometric parameters, and E median (P = .0007/<.0001/.0018/.0044/<.0001/<.0001/<.0001/<.0001/<.0001/.0204); and negatively with lymphocytes and HDL-cholesterol (r = -0.2747/-0.2181, P = .0116/.0120).Our study underlined significant differences between overweight and obese children in terms of inflammatory status and liver impairment suggesting that the risk is directly related to the increase in BMI.

In autoimmune liver disease (AILD), including autoimmune hepatitis (AIH), primary sclerosing cholangitis (PSC), and overlap syndrome of AIH and PSC (ASC), the presence of biliary injury portends a worse prognosis. We studied serum matrix metalloproteinase 7 (sMMP7) as a biomarker for pediatric sclerosing cholangitis (SC). We prospectively enrolled 54 children (median age, 16 years) with AILD (AIH, n = 26; ASC, n = 16; and PSC, n = 12) at our center. The sMMP7 concentrations were higher in patients with SC compared to those without cholangiopathy (P < 0.001). An sMMP7 concentration >23.7 ng/mL had a sensitivity and specificity of 79% and 96%, respectively, and outperformed alkaline phosphatase (ALP) and gamma-glutamyltransferase (GGT) in segregating patients with SC. Serum concentrations correlated with liver gene expression levels for MMP7 (r = 0.70; P < 0.001). Using immunofluorescence, MMP7 was localized primarily to the cholangiocytes of patients with SC. In 46 subjects with liver biopsy available for blinded review, elevation in sMMP7 concentrations segregated with the presence of lymphocytic and neutrophilic cholangitis and periductal fibrosis and correlated with Ishak, Ludwig, and Nakanuma scoring systems. Liver stiffness measured by magnetic resonance elastography also correlated with sMMP7 concentrations (r = 0.56; P < 0.01). Using magnetic resonance cholangiopancreatography plus (MRCP+), sMMP7 in 34 patients correlated with the number of biliary dilatations (r = 0.54; P < 0.01) and strictures (r = 0.56; P < 0.01). MMP7 as a marker of biliary injury was validated in an independent cohort of children with ulcerative colitis. Higher sMMP7 concentrations also correlated with a history of SC-related complication. Conclusion: MMP7 is a promising biomarker for pediatric SC that diagnostically outperforms ALP and GGT. sMMP7 may directly reflect biliary injury and fibrosis, the main drivers of disease progression in SC.

The Mediterranean diet (MD) has been found to lower the risk of heart disease, stroke, and diabetes in adults. Little is known about its acceptance and relationship to cardiovascular risk markers in US adolescents. Using data from the National Health and Nutrition Examination Survey, years 2007-2014, we performed a cross-sectional analysis of adherence to the Mediterranean diet among a representative sample of US adolescents (n = 4223), factors that influence adherence, and whether adherence is associated with cardiometabolic risk factors including metabolic syndrome. MD adherence was calculated using the KIDMED scoring system. We found that overall MD adherence was very low among US adolescents, with Mexican American youths having higher adherence compared to other groups. Higher income was associated with greater adherence. There was low intake of key MD foods including olive oil and finfish. The unadjusted prevalence of metabolic syndrome was 6.6%. MD adherence was not associated with metabolic syndrome.

Nonalcoholic fatty liver disease (NAFLD) has emerged as the leading cause of chronic liver disease in both adults and children. In this article, we review recent developments in the screening, diagnosis, and treatment of pediatric NAFLD.

Although alanine aminotransferase (ALT) remains the best screening test for NAFLD in children, and liver biopsy is still required for the diagnosis of nonalcoholic steatohepatitis (NASH), other noninvasive biomarker/imaging studies (MRI-PDFF and VCTE) have emerged as diagnostic methods for pediatric NAFLD. Two large clinical therapeutic trials testing vitamin E, metformin, and cysteamine in pediatric NAFLD yielded mostly inconclusive results. Bariatric surgery has begun to be used in adolescents with severe obesity. An adult phase 2 study using obeticholic acid (OCA) to treat NASH patients with fibrosis showed some positive results. As we continue to await the first FDA-approved therapeutic agent for NASH, lifestyle change remains the main modality of treatment. Newer diagnostic and treatment modalities for pediatric NAFLD continue to be in development under FDA guidance.

Gut microbiota dysbiosis has been repeatedly observed in obesity and type 2 diabetes mellitus, two metabolic diseases strongly intertwined with non-alcoholic fatty liver disease (NAFLD). Animal studies have demonstrated a potential causal role of gut microbiota in NAFLD. Human studies have started to describe microbiota alterations in NAFLD and have found a few consistent microbiome signatures discriminating healthy individuals from those with NAFLD, non-alcoholic steatohepatitis or cirrhosis. However, patients with NAFLD often present with obesity and/or insulin resistance and type 2 diabetes mellitus, and these metabolic confounding factors for dysbiosis have not always been considered. Patients with different NAFLD severity stages often present with heterogeneous lesions and variable demographic characteristics (including age, sex and ethnicity), which are known to affect the gut microbiome and have been overlooked in most studies. Finally, multiple gut microbiome sequencing tools and NAFLD diagnostic methods have been used across studies that could account for discrepant microbiome signatures. This Review provides a broad insight into microbiome signatures for human NAFLD and explores issues with disentangling these signatures from underlying metabolic disorders. More advanced metagenomics and multi-omics studies using system biology approaches are needed to improve microbiome biomarkers.

Non-alcoholic or recently re-defined metabolic associated fatty liver disease (MAFLD), a spectrum of progressive hepatic disease, has become a public health issue in obese children and adolescents. MAFLD is a complex metabolic disease strongly associated with obesity and insulin resistance. It is not known why not every obese subject will develop MAFLD. Different ethnic/racial groups display differences in MAFLD prevalence, indicating genetic factor plays a role. In the past two decades, sequence variations in genetic loci, including PNPLA3, TM6SF2, GCKR, MBOAT7, HSD17B13, etc. have been shown to confer susceptibility to MAFLD in children and adults. This review article provides an updated viewpoint of genetic predictors related to pediatric MAFLD. We discuss whether these susceptible genes can be clinically used for risk stratification and personalized care. Understanding human genetics and molecular mechanisms can give important information not only for prediction of risk but also on how to design drugs. In view of current epidemic of MAFLD worldwide, it is necessary to identify which children with MAFLD progress rapidly and need earlier intervention. In the future, a comprehensive analysis of individualized genetic and environmental factors may help assess the risk of children with MAFLD and personalize their treatment.

Screening nonalcoholic fatty liver disease (NAFLD) by body mass index (BMI) as a single surrogate measure for obesity has limitations. We suggest considering body composition zones by drawing a body composition chart composed of body composition indices, including BMI and percent body fat (PBF), to visualize the risk of NAFLD in obese children and adolescents.

Thirty-eight boys diagnosed with NAFLD were selected retrospectively from patients who visited Konkuk University Medical Center from 2006 to 2015. They had gone through body composition analysis by bioelectrical impedance analysis (BIA), and biochemical analyses, including a liver function test (LFT) and lipid panel, were performed. Fat-free mass index (FFMI) and fat mass index (FMI) were calculated from body composition analysis and height. We plotted FFMI and FMI of patients on a body composition chart and classified the patients into zones A to D. In addition, we analyzed the correlations between LFT, lipid panel, and body composition indices.

Thirty-three of 38 boys (86.8%) were located in zone C, corresponding to high BMI and PBF. Four boys (10.5%) were located in zone D, which correlates with sarcopenic obesity. One boy located in zone B was a muscular adolescent. Alanine aminotransferase level was positively correlated with PBF, FMI, and BMI z-score.

Body composition zones on a body composition chart might be useful in risk assessment in obesity-related diseases such as NAFLD. Zones on a body composition chart could have practical applications, especially in sarcopenic obese children and adolescents.

Sex differences are evident in the presentation of metabolic symptoms. A shift of sex hormones that signal the onset of puberty combined with a poor diet consumed in adolescence is likely to have sex-specific, long-term impacts on adult physiology. Here, we expanded on existing literature to elucidate the sex-specific mechanisms driving physiological deficits following high fructose consumption. Male and female Wistar rats were fed a high-fructose (55%) diet beginning immediately postweaning for 10 wk. Female rats fed the high-fructose diet displayed elevated weight gain and extensive liver pathology consistent with markers of nonalcoholic fatty liver disease (NAFLD). Male rats fed the high-fructose diet exhibited increased circulating glucose along with moderate hepatic steatosis. Levels of cytokines and gene expression of inflammatory targets were not altered by fructose consumption in either sex. However, circulating levels of markers for liver health, including alanine transaminase and uric acid, and markers for epithelial cell death were altered by fructose consumption. From the alterations in these markers for liver health, along with elevated circulating triglycerides, it was evident that liver health had deteriorated significantly and that a number of factors were at play. Both adult fructose-fed male and female rats displayed motor deficits that correlated with aberrant structural changes at the neuromuscular junction; however, these deficits were exacerbated in males. These data indicate that consumption of a high-fructose diet beginning in adolescence leads to adult pathology that is modified by sex. Identification of these sex-specific changes has implications for treatment of clinical presentation of metabolic syndrome and related disorders.

Body composition and hepatic fat correlate with future risk for metabolic syndrome. In children, many conventional techniques for quantifying body composition and hepatic fat have limitations. MRI is a noninvasive research tool to study body composition and hepatic fat in infants; however, conventional Cartesian MRI is sensitive to motion, particularly in the abdomen because of respiration. Therefore we developed a free-breathing MRI technique to quantify body composition and hepatic fat in infants.

In infants, we aimed to (1) compare the image quality between free-breathing 3-D stack-of-radial MRI (free-breathing radial) and 3-D Cartesian MRI in the liver and (2) determine the feasibility of using free-breathing radial MRI to quantify body composition and hepatic proton-density fat fraction (PDFF).

Ten infants ages 2-7 months were scanned with free-breathing radial (two abdominal; one head and chest) and Cartesian (one abdominal) MRI sequences. The median preparation and scan times were reported. To assess feasibility for hepatic PDFF quantification, a radiologist masked to the MRI technique scored abdominal scans for motion artifacts in the liver using a 3-point scale (1, or non-diagnostic, to 3, or no artifacts). Median visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT) and brown adipose tissue (BAT) volume and PDFF, and hepatic PDFF were measured using free-breathing radial MRI. We assessed repeatability of free-breathing radial hepatic PDFF (coefficient of repeatability) between back-to-back scans. We determined differences in the distribution of image-quality scores using McNemar-Bowker tests. P<0.05 was considered significant.

Nine infants completed the entire study (90% completion). For ten infants, the median preparation time was 32 min and scan time was 24 min. Free-breathing radial MRI demonstrated significantly higher image-quality scores compared to Cartesian MRI in the liver (radial scan 1 median = 2 and radial scan 2 median = 3 vs. Cartesian median = 1; P=0.01). Median measurements using free-breathing radial were VAT=52.0 cm³, VAT-PDFF=42.2%, SAT=267.7 cm³, SAT-PDFF=87.1%, BAT=1.4 cm³, BAT-PDFF=26.1% and hepatic PDFF=3.4% (coefficient of repeatability <2.0%).

In this study, free-breathing radial MRI in infants achieved significantly improved liver image quality compared to Cartesian MRI. It is feasible to use free-breathing radial MRI to quantify body composition and hepatic fat in infants.

This study had two main objectives: To examine the association between body fat distribution and non-alcoholic fatty liver disease (NAFLD) and liver fat content, and to determine whether the relationship between NAFLD and regional body fat distribution, with respect to liver fat content in youths with excess adiposity, is independent of cardiorespiratory fitness (CRF) and a healthy diet. Liver fat content (controlled attenuation parameter (CAP)), body fat distribution (body mass index (BMI) z-score, waist circumference, waist-to-height ratio, fat mass/height, body fat percentage, total fat mass, android-to-gynoid fat mass ratio, visceral adipose tissue (VAT), and lean mass index, determined by dual-energy X-ray absorptiometry (DXA)), CRF (20-m shuttle-run test), and healthy diet (adherence to the Mediterranean diet by KIDMED questionnaire) were measured in 126 adolescents (66% girls) aged between 11 and 17 years. Participants were assigned to two groups according to the presence or absence of hepatic steatosis (CAP values ≥225 dB/m or <225 dB/m of liver fat, respectively). Considering the similar total fat values for the two groups (>30% by DXA), youths with NAFLD had higher fat distribution parameters than those without NAFLD, regardless of sex, age, puberty stage, lean mass index, CRF, and healthy diet (p < 0.01). In the non-NAFLD group, the association between hepatic fat and fat distribution parameters presented a similar pattern, although the association was statistically insignificant after adjusting for a potential confounding variable (ps > 0.05), except for the case of VAT. Body fat distribution parameters were higher in youths with NAFLD compared to those without NAFLD. Additionally, body fat distribution showed a significant association with liver fat content as assessed by CAP in youths with NAFLD independent of CRF and adherence to the Mediterranean diet, supporting the notion that upper body fat distribution might play a pivotal role in the development of NAFLD in adolescents. These results may have implications for the clinical management of youths with excess adiposity given the high prevalence of NAFLD in children and young adults.

The prevalence of nonalcoholic fatty liver disease (NAFLD) has increased substantially in the past two decades and NAFLD has now become the most common cause of chronic liver disease in children and adolescents. NAFLD is a broad clinicopathologic spectrum ranging from simple steatosis to varying degrees of necroinflammation called nonalcoholic steatohepatitis (NASH), leading to fibrosis and subsequently to cirrhosis. Despite the increasing prevalence and progressive nature of NAFLD even among children, therapy for NAFLD in both adults and children are limited. Weight loss remains the only consistently effective therapy for NAFLD. Pharmacologic options are even more limited in children than in adults with NAFLD. Vitamin E has been shown to be effective in improving histology in children with NASH. Few pharmacologic options such as metformin, probiotics, omega-3 fatty acids, and cysteamine bitartrate have been studied in children, with limited beneficial effects. However, these studies are limited by small sample size and heterogeneity of outcome assessment after treatment. Recent studies show promising results with bariatric surgery with regards to weight loss and improvement in liver histology in adolescents with NAFLD. In this review article, we discuss epidemiology, pathophysiology, and extrahepatic comorbidities of pediatric NAFLD and review existing therapeutic options for children with NAFLD. We also review novel therapeutic strategies studied in adults that could potentially be studied in children in the future.

In adults, noninvasive chemical shift encoded Cartesian magnetic resonance imaging (MRI) and single-voxel magnetic resonance (MR) spectroscopy (SVS) accurately quantify hepatic steatosis but require breath-holding. In children, especially young and sick children, breath-holding is often limited or not feasible. Sedation can facilitate breath-holding but is highly undesirable. For these reasons, there is a need to develop free-breathing MRI technology that accurately quantifies steatosis in all children.

This study aimed to compare non-sedated free-breathing multi-echo 3-D stack-of-radial (radial) MRI versus standard breath-holding MRI and SVS techniques in a group of children for fat quantification with respect to image quality, accuracy and repeatability.

Healthy children (n=10, median age [±interquartile range]: 10.9 [±3.3] years) and overweight children with nonalcoholic fatty liver disease (NAFLD) (n=9, median age: 15.2 [±3.2] years) were imaged at 3 Tesla using free-breathing radial MRI, breath-holding Cartesian MRI and breath-holding SVS. Acquisitions were performed twice to assess repeatability (within-subject mean difference, MD_within). Images and hepatic proton-density fat fraction (PDFF) maps were scored for image quality. Free-breathing and breath-holding PDFF were compared using linear regression (correlation coefficient, r and concordance correlation coefficient, ρ_c) and Bland-Altman analysis (mean difference). P<0.05 was considered significant.

In patients with NAFLD, free-breathing radial MRI demonstrated significantly less motion artifacts compared to breath-holding Cartesian (P<0.05). Free-breathing radial PDFF demonstrated a linear relationship (P<0.001) versus breath-holding SVS PDFF and breath-holding Cartesian PDFF with r=0.996 and ρ_c=0.994, and r=0.997 and ρ_c=0.995, respectively. The mean difference in PDFF between free-breathing radial MRI, breath-holding Cartesian MRI and breath-holding SVS was <0.7%. Repeated free-breathing radial MRI had MD_within=0.25% for PDFF.

In this pediatric study, non-sedated free-breathing radial MRI provided accurate and repeatable hepatic PDFF measurements and improved image quality, compared to standard breath-holding MR techniques.

Hepatic steatosis is an abnormal state where excess lipid mass is accumulated in hepatocyte vesicles. Backscattered ultrasound signals received from the liver contain useful information regarding the degree of steatosis in the liver. The homodyned-K (HK) distribution has been demonstrated as a general model for ultrasound backscattering. The estimator based on the first three integer moments (denoted as "FTM") of the intensity has potential for practical applications because of its simplicity and low computational complexity. This study explored the diagnostic performance of HK parametric imaging based on the FTM method in the assessment of hepatic steatosis. Phantom experiments were initially conducted using the sliding window technique to determine an appropriate window size length (WSL) for HK parametric imaging. Subsequently, hepatic steatosis was induced in male Wistar rats fed a methionine- and choline-deficient (MCD) diet for 0 (i.e., normal control), 1, 2, 4, 6, and 8 weeks (n = 36; six rats in each group). After completing the scheduled MCD diet, ultrasound B-mode and HK imaging of the rat livers were performed in vivo and histopathological examinations were conducted to score the degree of hepatic steatosis. HK parameters μ (related to scatterer number density) and k (related to scatterer periodicity) were expressed as functions of the steatosis stage in terms of the median and interquartile range (IQR). Receiver operating characteristic (ROC) curve analysis was conducted to assess the diagnostic performance levels of the μ and k parameters. The results showed that an appropriate WSL for HK parametric imaging is seven times the pulse length of the transducer. The median value of the μ parameter increased monotonically from 0.194 (IQR: 0.18-0.23) to 0.893 (IQR: 0.64-1.04) as the steatosis stage increased. Concurrently, the median value of the k parameter increased from 0.279 (IQR: 0.26-0.31) to 0.5 (IQR: 0.41-0.54) in the early stages (normal to mild) and decreased to 0.39 (IQR: 0.29-0.45) in the advanced stages (moderate to severe). The areas under the ROC curves obtained using (μ, k) were (0.947, 0.804), (0.914, 0.575), and (0.813, 0.604) for the steatosis stages of ≥mild, ≥moderate, and ≥severe, respectively. The current findings suggest that ultrasound HK parametric imaging based on FTM estimation has great potential for future clinical diagnoses of hepatic steatosis.

Nonalcoholic fatty liver disease (NAFLD) can develop in lean subjects referred to as lean NAFLD. We aim to evaluate the prevalence and risk factors of NAFLD in lean adolescents in the United States (US).

Cross sectional data from 1482 lean subjects (body mass index <85th percentile) ages between 12 and 18 years, who were enrolled in the National Health and Examination Survey during the 2005 to 2014 cycles were included. We defined suspected NAFLD as alanine aminotransferase >25.8 U/L for boys and >22.1 U/L for girls; hypertriglyceridemia as triglycerides ≥150 mg/dL; low HDL as HDL <40 mg/dL and insulin resistance (IR) as homeostatic model assessment of IR ≥3.

The mean weighted prevalence of suspected NAFLD among lean adolescents during 2005 to 2014 cycles was 8% (95% CI 6.2-9.9). Lean subjects with suspected NAFLD were significantly older compared with lean non-NAFLD subjects (15.5 vs 15 years, P value <0.05). Low HDL (15.5% vs 6.8%; P value 0.016) and hypertriglyceridemia (10% vs 3.9%; P value 0.028) were also found to be more common among lean NAFLD subjects compared with their non-NAFLD counterparts. Presence of IR increased the risk of having suspected NAFLD by 4-fold among lean adolescents. Non-Hispanic black lean adolescents were less likely to have suspected NAFLD compared with non-Hispanic white lean adolescents.

The estimated prevalence of suspected NAFLD among lean adolescents in the US was found to be 8% with evidence of metabolic derangements such as low HDL, hypertriglyceridemia, and IR.

This study aimed to evaluate the impact of physical activity (PA) on the course of hepatic steatosis (HS) in adults.

Hepatic steatosis status (ultrasonography) and PA levels were evaluated in 5860 subjects at baseline and after approximately 2.5 years (range: 19-50 months). At follow up, possible exposures to different PA levels were those who remained inactive, became inactive, became active, and remained active. After follow up, subjects were then classified according to the four possible states (outcomes): "remained without HS," "developed HS" (subjects without HS at baseline), "remained with HS," or "reverted HS."

After multivariate adjustments, individuals without HS that became or remained physically active were less likely to develop HS compared with those who remained physically inactive (odds ratio = 0.75, P = 0.04 and 0.75, P = 0.03, respectively). Among those with HS at baseline, becoming and remaining physically active beneficially improved the HS status (odds ratio = 0.64, P = 0.01 and 0.66, P = 0.01, respectively). However, the significance was lost when adjusted for changes in body mass index.

Higher levels of PA were associated with prevention and treatment of HS, with evidence of effect mediation by changes in body mass index.

Ultrasound B-mode imaging based on log-compressed envelope data has been widely applied to examine hepatic steatosis. Modeling raw backscattered signals returned from the liver parenchyma by using statistical distributions can provide additional information to assist in hepatic steatosis diagnosis. Since raw data are not always available in modern ultrasound systems, information entropy, which is a widely known nonmodel-based approach, may allow ultrasound backscattering analysis using B-scan for assessing hepatic steatosis. In this study, we explored the feasibility of using ultrasound entropy imaging constructed using log-compressed backscattered envelopes for assessing hepatic steatosis. Different stages of hepatic steatosis were induced in male Wistar rats fed with a methionine- and choline-deficient diet for 0 (i.e., normal control) and 1, 1.5, and 2 weeks (n = 48; 12 rats in each group). In vivo scanning of rat livers was performed using a commercial ultrasound machine (Model 3000, Terason, Burlington, MA, USA) equipped with a 7-MHz linear array transducer (Model 10L5, Terason) for ultrasound B-mode and entropy imaging based on uncompressed (H_E image) and log-compressed envelopes (H_B image), which were subsequently compared with histopathological examinations. Receiver operating characteristic (ROC) curve analysis and areas under the ROC curves (AUC) were used to assess diagnostic performance levels. The results showed that ultrasound entropy imaging can be used to assess hepatic steatosis. The AUCs obtained from H_E imaging for diagnosing different steatosis stages were 0.93 (≥mild), 0.89 (≥moderate), and 0.89 (≥severe), respectively. H_B imaging produced AUCs ranging from 0.74 (≥mild) to 0.84 (≥severe) as long as a higher number of bins was used to reconstruct the signal histogram for estimating entropy. The results indicated that entropy use enables ultrasound parametric imaging based on log-compressed envelope signals with great potential for diagnosing hepatic steatosis.

Background Acoustic radiation force impulse (ARFI) is a non-invasive alternative to a liver biopsy for the evaluation of liver fibrosis (LF). Purpose To investigate the potential usefulness of acoustic radiation force impulse ARFI for detecting LF in overweight and obese children Material and Methods A cross-sectional study was conducted in 148 schoolchildren. A diagnosis of non-alcoholic fatty liver disease (NAFLD) and LF was based on ultrasound (US) and ARFI shear wave velocity (SWV). Results The laboratory parameters were normal in all the children. NAFLD was observed in 50 children (33.8%). The median SWV was 1.18 ± 0.28 m/s. Differences between ARFI categories and hepatic steatosis grades were observed (χ2 = 43.38, P = 0.0005). No fibrosis or insignificant fibrosis (SWV ≤ 1.60 m/s) was detected in 137 children (92.5%), and significant fibrosis (SWV > 1.60 m/s) in 11 children (7.5%), nine of whom had normal US or mild steatosis. Conclusion The present study is the first to evaluate the utility of the ARFI technique for detecting LF in overweight and obese children. The results of the study suggest that children with normal laboratory parameters such as normal liver ultrasound or mild steatosis may present with significant LF.

Nonalcoholic fatty liver disease (NAFLD) is currently the most common cause of chronic liver disease worldwide and is present in a third of the general population and the majority of individuals with obesity and type 2 diabetes. Importantly, NAFLD can progress to severe nonalcoholic steatohepatitis (NASH), associated with liver failure and hepatocellular carcinoma. Recent research efforts have extensively focused on identifying factors contributing to the additional "hit" required to promote NALFD disease progression. The maternal diet, and in particular a high-fat diet (HFD), may be one such hit "priming" the development of severe fatty liver disease, a notion supported by the increasing incidence of NAFLD among children and adolescents in Westernized countries. In recent years, a plethora of key studies have used murine models of maternal obesity to identify fundamental mechanisms such as lipogenesis, mitochondrial function, inflammation, and fibrosis that may underlie the developmental priming of NAFLD. In this chapter, we will address key considerations for constructing experimental models and both conventional and advanced methods of quantifying NAFLD disease status.