Search Results (94)

Background: The presence of metabolic syndrome (MetS) in children predisposes them to steatotic liver disease, with or without liver enzyme alterations. Early diagnosis of the degree of liver damage can stop the progression to more severe dysfunction. Objectives: This study aimed to establish the link between liver enzyme levels and triglyceride and cholesterol values in pediatric patients with obesity, grouped according to MetS status and metabolic dysfunction-associated fatty liver disease (MAFLD). Methods: The retrospective observational study included 261 pediatric patients aged between 0 and 18 years diagnosed with obesity, MetS, and MAFLD. Before initiating the study, approval was obtained from the hospital’s Ethics Committee. The clinical and biochemical data were collected from the patients’ histories. Results: Alanine aminotransferase showed a significant positive correlation with triglyceride levels in the overall cohort, which became stronger in children with MetS and was strongest in those with ultrasonographically confirmed MAFLD. Similarly, aspartate aminotransferase demonstrated a weak positive correlation with triglycerides in the overall population, which increased in patients with MetS and became strong in children with MAFLD. Conclusions: In children with MetS and ultrasound-diagnosed MAFLD, liver enzymes showed progressively stronger positive correlations with triglyceride levels, indicating a close link between dyslipidemia and liver damage. Associations between liver enzymes and total cholesterol further support metabolic dysregulation, rather than body mass index alone, as a key driver of pediatric steatotic liver disease and highlight the value of targeted liver enzyme assessment in children with MetS or hypertriglyceridemia. Full article

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD), previously known as non-alcoholic fatty liver disease (NAFLD), is increasingly prevalent in children. However, reliable noninvasive diagnostic tools remain limited. The hepatorenal index (HRI) has been proposed as a quantitative ultrasound method to assess hepatic steatosis. This study aims to evaluate the diagnostic accuracy of HRI in detecting pediatric MASLD. Methods: A systematic review and meta-analysis were conducted on 13 September 2025, following PRISMA-DTA guidelines, with the protocol registered in PROSPERO (CRD420251146939). MEDLINE, PubMed, Cochrane Library, ScienceDirect, and Google Scholar were searched. Studies that assessed HRI against reference standards (MRI-PDFF or liver biopsy) in pediatric MASLD were included. Pooled diagnostic parameters were estimated using a bivariate random-effects model, with heterogeneity evaluated by I² statistics and publication bias by funnel plot asymmetry. Results: Four studies involving 194 pediatric patients (47.9% MASLD), mostly male (57.7%), met the inclusion criteria. The suggested HRI cut-off varies from ≥1.215 to 1.99. The pooled sensitivity and specificity were 90% (95% CI 70–97) and 84% (95% CI 73–92), respectively, with an AUC of 0.91 (95% CI 0.88–0.93). Positive and negative likelihood ratios were 6 and 0.12, corresponding to post-test probabilities of 32% and 1%, respectively. No significant publication bias or heterogeneity was detected. Conclusions: Although HRI demonstrates strong diagnostic performance, it currently lacks sufficient discriminatory power to definitively confirm or exclude MASLD in pediatric populations and should therefore be regarded as a supportive rather than definitive diagnostic tool pending further high-quality validation studies. Full article

Background/Objectives: To examine the association between metabolic dysfunction–associated fatty liver disease (MAFLD) and bone mineral density in school-aged children. To investigate the association between metabolic dysfunction-associated fatty liver disease (MAFLD) and bone mineral density among school-aged children using a propensity score-matched study design. Methods: A cross-sectional analysis was performed using baseline data from the Beijing Children and Adolescents Health Cohort, with samples collected between September 2022 and May 2023. The study included 5170 children aged 7–18 years. Standardized questionnaires collected behavioral, lifestyle, and dietary data. Anthropometric measurements (height, weight, waist circumference) were obtained to calculate body mass index (BMI). Fasting venous blood samples were analyzed for glucose and lipid profiles. Clinical assessments included pubertal development evaluation, abdominal ultrasound for hepatic steatosis, oscillometric blood pressure measurement, quantitative ultrasound for calcaneal bone mineral density (BMD), and bioelectrical impedance analysis for body fat percentage. MAFLD was diagnosed as hepatic steatosis combined with metabolic abnormalities (assessed via BMI, blood glucose, lipid levels, and blood pressure). Propensity score matching (PSM) was conducted at a 1:3 ratio between the MAFLD and non-MAFLD groups, matching on age, sex, and pubertal stage. Multiple linear regression, conditional logistic regression, and quantile regression (10th–90th percentiles) were used to analyze the association between MAFLD and BMD. Results: Of 5170 participants, 579 had MAFLD and were matched to 1737 non-MAFLD controls (standardized mean differences < 0.001). Children with MAFLD had higher BMI, body fat percentage, and waist circumference, and lower BMD versus controls. Multiple linear regression confirmed a significant negative association between MAFLD and BMD, which was stronger in boys and mid-pubertal children. Conditional logistic regression analyses further showed that boys with MAFLD had a higher risk of reduced BMD. The odds ratios were 1.77 (95% CI: 1.14–2.75) overall, 2.74 (95% CI: 1.56–4.81) among those aged 12–14 years, 1.81 (95% CI: 1.04–3.17) in mid-puberty, and 2.27 (95% CI: 1.17–4.40) in late puberty. Quantile regression revealed the strongest associations between MAFLD and BMD at the 40th–75th percentiles (regression coefficients: −9.5 to −6.7). Conclusions: MAFLD was associated with lower bone mineral density in children, with the strongest associations observed in the lower-to-middle range. Boys, children in mid-puberty, and those with obesity may represent particularly vulnerable groups with respect to bone health in the presence of MAFLD. This highlights the importance of early MAFLD identification and targeted interventions to mitigate long-term skeletal risks. Prospective studies are needed to clarify the causal pathways between MAFLD and pediatric bone health, and future research should integrate multiple factors to elucidate the underlying mechanisms. Full article

Childhood overweight and obesity represent a major global public health emergency, with a steadily increasing prevalence over recent decades in both developed and developing countries. Approximately one fifth of children and adolescents are overweight or obese, with marked differences across ethnic groups and geographical areas. Accurate estimation of this condition is complicated by the lack of a unique and universally accepted definition of childhood obesity, which is based on different anthropometric criteria. Although body mass index (BMI) remains the most widely used tool, growing evidence indicates that abdominal obesity, assessed by waist circumference and waist-to-height ratio, is a better predictor of cardiometabolic risk, even in children with a normal BMI. Childhood obesity is associated with several comorbidities, including arterial hypertension, non-alcoholic fatty liver disease (NAFLD) and obstructive sleep apnea syndrome (OSAS). Early diagnosis and an integrated therapeutic approach are essential to reduce the risk of long-term complications. Although lifestyle modifications remain the cornerstone of treatment, new pharmacological options for pediatric obesity have been approved in recent years. This narrative review explores the impact of childhood obesity on the early development of hypertension, NAFLD, and OSAS, emphasizing the implications that can already be observed during childhood and adolescence. It examines the association between pediatric obesity and these conditions by synthesizing current epidemiological evidence, describing the underlying pathophysiological mechanisms linking excess adiposity to disease onset, and reviewing pediatric-specific diagnostic criteria as well as preventive and therapeutic strategies. Full article

The increasing prevalence of metabolic dysfunction-associated fatty liver disease (MASLD) in children requires robust, non-invasive biomarkers to enable accurate disease staging and risk stratification. Elevated serum levels of homocysteine (Hcy) have emerged as potential risk factors for cardiometabolic disease in adults, including MASLD. In this observational retrospective study, we investigated the role of serum Hcy levels as a potential biomarker for disease severity and liver fibrosis in a pediatric cohort of 182 children with MASLD. In 89 patients, liver biopsy allowed the classification into metabolic dysfunction-associated steatohepatitis (MASH). Associations between Hcy, metabolic parameters, fibrosis scores, and histological features were examined, and the diagnostic performance of Hcy for liver fibrosis was evaluated using ROC analysis. Multivariate analyses identified elevated Hcy levels as independently associated with HOMA-IR (β = 0.55; p = 0.049), TG/HDL ratio (β = 3.23; p = 0.002), and liver fibrosis (β = 2.59; p = 0.04). Hcy showed a predictive accuracy of 81% for fibrosis. However, the combined diagnostic models of Hcy with non-invasive fibrotic scores (i.e., APRI and FIB-4) or TG/HDL ratio showed only a modest accuracy (AUC = 0.62–0.69). In conclusion, our data suggest that Hcy is associated with fibrosis and cardiometabolic risk. However, these results should be interpreted as exploratory and do not establish homocysteine as a diagnostic biomarker. Full article

Background: Childhood obesity represents the most common nutritional and metabolic disorder in industrialized countries and constitutes a major public health concern. In Italy, 20–25% of school-aged children are overweight and 10–14% are obese, with marked regional variability. Excess adiposity in childhood is frequently associated with hypertension, dyslipidemia, insulin resistance, and non-alcoholic fatty liver disease (NAFLD), predisposing to future cardiovascular disease (CVD). Objective: To investigate anthropometric indicators of cardiometabolic risk in 810 children and adolescents aged 7–17 years who underwent assessment for competitive sports eligibility at the Sports Medicine Unit of Modena, evaluate baseline knowledge of cardiovascular health aligned with ESC, AAP (2023), and EASO guidelines. Methods: 810 children and adolescents aged 7–17 years undergoing competitive sports eligibility assessment at the Sports Medicine Unit of Modena underwent evaluation of BMI percentile, waist circumference (WC), waist-to-height ratio (WHtR), and blood pressure. Cardiovascular knowledge and lifestyle habits were assessed via a previously used questionnaire. Anthropometric parameters, blood pressure (BP), and lifestyle-related knowledge and behaviors were assessed using standardized procedures. Overweight and obesity were defined according to WHO BMI-for-age percentiles. Elevated BP was classified based on the 2017 American Academy of Pediatrics age-, sex-, and height-specific percentiles. Statistical analyses included descriptive statistics, group comparisons, chi-square tests with effect size estimation, correlation analyses, and multivariable logistic regression models. Results: Overall, 22% of participants were overweight and 14% obese. WHtR > 0.5 was observed in 28% of the sample and was more frequent among overweight/obese children (p < 0.001). Elevated BP was detected in 12% of participants with available measurements (n = 769) and was significantly associated with excess adiposity (χ² = 7.21, p < 0.01; Cramér’s V = 0.27). In multivariable logistic regression analyses adjusted for age and sex, WHtR > 0.5 (OR 2.14, 95% CI 1.32–3.47, p = 0.002) and higher sedentary time (OR 1.41 per additional daily hour, 95% CI 1.10–1.82, p = 0.006) were independently associated with elevated BP, whereas BMI percentile lost significance when WHtR was included in the model. Lifestyle knowledge scores were significantly lower among overweight and obese participants compared with normal-weight peers (p < 0.01). Conclusions: WHtR is a sensitive early marker of cardiometabolic risk, often identifying at-risk children missed by BMI alone. Baseline cardiovascular knowledge was suboptimal. The observed gaps in cardiovascular knowledge underscore the importance of integrating anthropometric screening with structured educational interventions to promote healthy lifestyles and long-term cardiovascular prevention. Full article

Lipids are essential biomolecules involved in membrane structure, energy storage, and intracellular signaling. Dysregulation of lipid metabolism (dyslipidemia) plays a central role in a wide spectrum of pediatric metabolic disorders, including both inherited and acquired conditions. Recent and rapid advances in mass spectrometry-based lipidomics have enabled high-resolution profiling of more than one-thousand lipid species, facilitating the discovery of disease-specific lipid signatures that were previously undetectable with conventional biochemical assays. In parallel, the rising prevalence of pediatric obesity, diabetes, asthma, metabolic dysfunction-associated steatotic liver disease (MASLD; formerly referred to as non-alcoholic fatty liver disease or NAFLD) and cancers has accelerated research aimed at uncovering molecular pathways underlying these conditions. Lipidomic approaches have also improved the identification and characterization of rare metabolic disorders. As analytical technologies continue to advance, lipidomics is poised to become a cornerstone of precision medicine in pediatrics, offering new opportunities for early diagnosis, risk stratification, and therapeutic targeting. Full article

Non-alcoholic fatty liver disease (NAFLD) is the most common pediatric chronic liver disease worldwide, with an increasing prevalence, mainly due to the increase in childhood obesity and sedentary lifestyle. The pathogenesis of NAFLD is multifactorial, but the mechanisms by which the factors involved, namely the genetic, intrauterine and environmental factors responsible for its onset and progression to NASH, are not fully known. Children with NAFLD are usually asymptomatic or show nonspecific symptoms, and NAFLD is generally diagnosed incidentally by screening tests in overweight or obese children. NAFLD is associated with severe metabolic deficiencies that may progress to cirrhosis and hepatocellular carcinoma, with the consequent need for liver transplantation. Current treatment of NAFLD in children consists of lifestyle changes to decrease caloric intake and increase physical activity, with no currently approved pharmacological medication for the pediatric population. Although pediatric studies that focus on alternative treatments targeting key pathogenic factors are promising, no pharmacological agent is currently approved for children, validated non-invasive fibrosis biomarkers remain limited, and long-term outcome data are scarce. Further validation through large prospective pediatric cohorts and phase III trials is urgently needed. Full article

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most prevalent chronic liver disorder in both children and adults. Pediatric MASLD, however, is not simply an early form of adult disease, as it exhibits distinct developmental, histological, and metabolic features. Emerging evidence suggests that these characteristics arise from a complex, multi-hit continuum that begins in utero. Maternal obesity, gestational diabetes, and poor diet quality during pregnancy have been associated with greater hepatic steatosis in offspring, raising the possibility that intrauterine exposure to dyslipidemia, hyperglycemia, and elevated free fatty acid flux may contribute to early hepatic lipid deposition. After birth, feeding behaviors such as a prolonged breastfeeding appear protective, whereas formula feeding, especially high added-sugar formulations, may accelerate rapid weight gain and increase susceptibility to later steatosis. Early childhood diets high in added sugars, saturated fats, and ultra-processed foods may further promote hepatic lipogenesis and inflammation and interact with underlying genetic susceptibility. Given the heterogeneity of available human cohort studies and mechanistic model systems, this narrative review summarizes converging evidence from prenatal, postnatal, and early childhood nutritional exposures and their relationship to offspring hepatic lipid accumulation, emphasizing early-life windows for intervention to reduce the burden of pediatric MASLD. Full article

Metabolic dysfunction–associated fatty liver disease (MAFLD) is now the leading indication for liver transplantation (LT), reshaping the landscape of transplant hepatology. Its close association with obesity, type 2 diabetes, cardiovascular disease, and extrahepatic malignancies poses unique challenges throughout the transplant continuum. This narrative review synthesizes current evidence across the pre-, peri-, and post-transplant spectrum, with a focus on practical implications for clinical management. We explore pre-transplant evaluation, focusing on how metabolic comorbidities, frailty, and organ allocation disparities intersect with emerging interventions such as GLP-1 receptor agonists, bariatric surgery, and structured weight loss programs. The increase in pediatric MAFLD, especially its early-onset aggressive form, indicates an evolving and concerning future burden on transplant programs. In the peri-operative and post-transplant periods, we address MAFLD recurrence, cardiometabolic complications, and the rising incidence of new cancers, particularly in relation to calcineurin inhibitor (CNI) exposure. Customized immunosuppression strategies, using mTOR inhibitors and mycophenolate mofetil, are discussed for their role in balancing graft protection with reducing cancer risk. We also review the application of machine perfusion technologies to optimize and expand the pool of steatotic donor livers. Future directions include the development of non-invasive diagnostic biomarkers, precision immunosuppression, and genomics-based risk stratification. Collectively, these insights emphasize the urgent need for multidisciplinary, patient-specific approaches and prospective, multicenter studies to optimize outcomes and equity in the era of MAFLD-driven liver transplantation. Full article

In contrast to several high-income nations, childhood obesity prevalence is rising in low/middle-income countries. Our objective was to study risk factors and complications of childhood overweight/obesity in an urban lower middle-income country setting. This was an observational study. Children aged 2–18 years at a pediatric clinic in Chennai, India were enrolled over a 12-month period. The definition of overweight was >23rd and obesity >27th adult equivalent percentile Body Mass Index. Parents and children completed a risk-factor questionnaire. Children with obesity/overweight were evaluated for complications. Of 103 children enrolled, 61% were obese/overweight and 39% healthy weight. Independent predictors of absence of overweight/obesity were as follows: never/rarely consuming sugar-sweetened beverages, never/rarely eating out, and sleep duration > 11 h. Exercise performed rarely/never independently predicted overweight/obesity. No significant difference was observed with screen time or a vegetarian diet. Complications in 54 obese/overweight children included prediabetes (15%), hypertension (11%), dyslipidemia (22%), nonalcoholic fatty liver disease (22%), acanthosis nigricans (24%), and anxiety/depression (17%). In conclusion, differences were observed in behaviors associated with childhood obesity in an urban lower middle-income environment compared to those in high-income nations. Behaviors associated with childhood obesity in an urban lower middle-income environment are similar to those reported from high-income nations, with some differences. Complications of overweight/obesity are common in this setting. Full article

Aim: This current research aims to determine the predictive value of the ratio of triglyceride (TG)/high-density lipoprotein cholesterol (HDL-C), index of triglyceride–glucose (TyG), homeostatic model assessment for insulin resistance (HOMA-IR) score, and anthropometric measurements at the onset of non-alcoholic fatty liver disease (NAFLD) in obese kids and juveniles. It also sought to assess how novel cardiovascular risk markers are affected in obese pediatric patients with NAFLD. Materials and Methods: Between November 2024 and May 2025, a total of 199 pediatric patients were prospectively evaluated, including 150 children with obesity and 49 entirely healthy controls. Two categories of obese patients were created based on whether or not they had non-alcoholic fatty liver disease. These groups were compared with each other and with the control group in terms of HOMA-IR score, index of TyG, ratio of TG/HDL-C, anthropometric parameters (percentage of body fat [BFP], index of body mass [BMI], body fat mass [BFM], waist circumference [WC]), and cardiovascular risk markers. The cutoff values, sensitivity, and specificity of the HOMA-IR score, ratio of TG/HDL-C, anthropometric measurements, and index of TyG in predicting NAFLD were assessed using Receiver Operating Characteristic (ROC) analysis. Results: Obese kids and juveniles with NAFLD had significantly higher TG/HDL-C ratios, TyG indices, HOMA-IR scores, anthropometric measurements, and cardiovascular risk markers than those without NAFLD (p < 0.001). The TG/HDL-C ratio (AUC: 0.936; 81.8% sensitivity, 95.9% specificity) and the TyG index (AUC: 0.912; 81.8% sensitivity, 91.8% specificity) showed strong predictive value for NAFLD, while HOMA-IR and WC were found to be relatively weaker predictors. Conclusions: The index of TyG and ratio of TG/HDL-C are highly effective parameters in predicting NAFLD development in obese kids and juveniles. Those with increased WC and BFP should be closely monitored for NAFLD development. Pediatric patients with NAFLD should be carefully followed up for potential cardiovascular diseases. Full article

Emerging evidence highlights extracellular vesicles (EVs), especially exosomes, as critical molecular messengers linking pediatric obesity to multi-organ complications. This scoping review synthesizes current knowledge on EVs-mediated intercellular communication that exacerbates inflammation, insulin resistance, endothelial dysfunction and organ-specific damage. Data demonstrate that adipose- and endothelial-derived EVs carry bioactive cargo, microRNAs, proteins, and lipids, that modulate key pathways driving metabolic derangements and vascular injury, often preceding detectable clinical biomarkers. Notably, maternal obesity influences EVs composition in breast milk, shaping early-life metabolic programming and offspring risk of obesity. Recent studies underscore the diagnostic and therapeutic potential of EVs in obesity-related conditions such as metabolic-associated fatty liver disease (MAFLD), early renal injury, and cardiovascular dysfunction in children. Furthermore, EVs released in response to exercise or bariatric surgery may mediate systemic metabolic improvements, offering a novel window into personalized interventions. Despite promising findings, standardization of EV isolation and profiling in pediatric research is lacking, and large-scale longitudinal studies are urgently needed. By deepening our understanding of EVs biology, clinicians may advance early detection, risk stratification, and targeted therapies to interrupt the progression from childhood obesity to lifelong metabolic and cardiovascular disease. Full article

Over the past century of research, it has become increasingly evident that glucagon should no longer be regarded solely as a counter-regulatory hormone to insulin. Its role in the pathophysiology of metabolic disorders—including diabetes, obesity, and non-alcoholic fatty liver disease—appears to be critical. Hyperglucagonemia is a common feature across several metabolic conditions, not only in adults but also in pediatric populations, suggesting that glucagon may represent both a pathogenic factor and a potential therapeutic target in metabolic disease. Accordingly, therapeutic strategies have been developed that either inhibit or enhance glucagon activity, depending on the clinical context, and some of these approaches are being applied in pediatric care as well. This review aims to provide a comprehensive overview of the pathophysiological role of glucagon in metabolic diseases, synthesizing recent findings that support novel hypotheses for the management and prevention of these conditions. Full article

Metabolic dysfunction-associated steatotic liver disease (MASLD)—previously known as non-alcoholic fatty liver disease (NAFLD)—is currently the most common chronic liver disease globally. Observational studies have reported that MASLD is independently associated with extrahepatic disorders, such as chronic kidney disease (CKD). Severe forms of MASLD (i.e., steatohepatitis and liver fibrosis) are even more strongly associated with the risk of incident kidney dysfunction. Hypothetically, MASLD could directly promote CKD through liver-derived endocrine and metabolic mediators, hemodynamic alterations, immune-mediated mechanisms, and oxidative or cellular stress. However, proving that MASLD directly causes CKD is difficult due to the multiple shared cardiometabolic and systemic risk factors, such as obesity, hypertension, and type 2 diabetes mellitus, which serve as confounding variables. Moreover, studies on the association between MASLD and CKD have differed in their designs, sampling methods, disease definitions, and inclusion criteria, precluding more robust evidence supporting a causal relationship. Furthermore, few studies have explored specific issues, such as the new nomenclature for steatotic liver disease, the relationship between these diseases in pediatric populations, the impact of MASLD plus alcohol intake (MetALD) on CKD, and therapeutic options targeting MASLD and CKD simultaneously. Answers to these issues are essential, as the appropriate management of patients with MASLD may prevent or ameliorate kidney dysfunction. The aims of the present study are to describe shared risk factors between MASLD and CKD, the possible direct pathogenic effect of MASLD on kidney structure and function, and gaps in the current literature, to indicate future research directions. Full article