Graphical abstract. NAFLD, nonalcoholic fatty liver disease; MASLD, metabolic dysfunction-associated steatotic liver disease; BMI, body mass index; ALT, alanine aminotransferase
Introduction
Metabolic dysfunction-associated steatotic liver disease (MASLD) in children has emerged as a significant global health concern and one of the common causes of chronic liver disease in children and adults. The global prevalence in the general pediatric population is 3%–10% [1]. A meta-analysis of 2,903 children found an overall prevalence of 35.4%, including 12.4% in nonobese and 63.5% in obese children [2]. Over the past decade, the understanding of MASLD has evolved, leading to the updated guidelines. This update provides key information for pediatricians to understand, diagnose, and manage this condition based on the latest guidelines by the Indian Society of Pediatric Gastroenterology, Hepatology, and Nutrition (ISPGHAN) (Table 1).
ISPGHAN developed recommendations through a literature review and evidence grading based on the American Academy of Pediatrics guidelines. Key questions were assigned to experts, and findings were discussed at a consensus meeting, leading to finalized, evidence-based clinical guidelines.
New nomenclature and paediatrician specific aspect
The term nonalcoholic fatty liver disease (NAFLD) has been used for the past 30 years but was based on negative criteria- a diagnosis of exclusion. Terms like “nonalcoholic” and "fatty" are stigmatizing and can lead to underreporting. Moreover, the term fails to describe the underlying pathophysiology that is metabolic dysfunction, primarily driven by insulin resistance. The new term, MASLD is more pathophysiologically accurate and less stigmatizing. For pediatricians, it is important to understand that in context of MASLD “metabolic” refers to cardiometabolic abnormalities and not the inborn error of metabolism.
Cardiometabolic criteria
MASLD in children is often asymptomatic or presents with mild, nonspecific symptoms. It is usually associated with cardiometabolic factors (hypertension, insulin resistance/diabetes mellitus, and/or dyslipidemia). Most of the children found on screening for obesity. Indian guidelines recommend screening of all obese (body mass index [BMI] >95th centile) and overweight (BMI >85th centile) with additional risk factors—prediabetes/diabetes, dyslipidemia, waist circumference (WC) greater than 70th percentile, hypertension, positive family history of metabolic syndrome, obstructive sleep apnea, and hypopituitarism.
Hepatic steatosis (imaging or biopsy) along with presence of one out of five pediatric cardiometabolic criteria is required for diagnosis in absence of other causes of hepatic steatosis.
(1) BMI ≥85th percentile for age/sex (BMI z score ≥+1) or WC >95th percentile (ethnicity-adjusted)
(2) Elevated fasting serum glucose ≥100 mg/dL or 2-hour glucose tolerance test glucose ≥140 mg/dL or hemoglobin A1c (HbA1c) ≥5.7% or diagnosed/treated type 2 diabetes (2-hour glucose tolerance test glucose ≥200 mg/dL or HbA1c ≥6.5
(3) Blood pressure age <13 years, BP ≥95th percentile or ≥ 130/80 mmHg (whichever is lower); age ≥13 years, 130/85 mmHg or specific antihypertensive drug treatment
(4) Plasma/serum triglycerides: if <10-years-old, >100 mg/dl; if >10 years, >150 mg/dL or lipid lowering treatment
(5) Plasma HDL 40 mg/dL or lipid lowering treatment Diagnostic and screening tools
1. Alanine aminotransferase
Alanine aminotransferase (ALT) has been commonly used for screening but lacks specificity as it may be normal in mild cases. No established Indian cutoff. As per SAFETY study data [3], the optimal cutoff is 26 IU/L for boys and 22 IU/L for girls (aged 12–18 years). ALT >2 × upper limit of normal is considered significant.
2. Ultrasound
Ultrasound (USG) finding indicating steatosis is a brighter liver as compared to hypoechoic renal parenchyma. It has high sensitivity and specificity if >33% hepatocytes are involved. But low sensitivity when steatosis involve <30% hepatocytes. Indian guideline recommends using both USG and ALT for screening.
3. Role of transient elastography
Transient elastography (TE) (FibroScan) assesses liver stiffness and steatosis with good diagnostic accuracy. Indian guidelines endorse its use for diagnosing and monitoring fibrosis and steatosis.
4. Liver biopsy
Liver biopsy remains the most definitive method for assessing the degree of steatosis, inflammation, and fibrosis, its invasive nature, risk of complications, and sampling variability limit its routine use in children. Therefore, it is recommended for the obese/overweight children with suspected MASLD <8 years of age and/or where there is a high suspicion of advanced disease and/or if an alternative diagnosis is considered.
Management
The cornerstone of management is lifestyle modification, particularly weight loss through diet and exercise.
2. Exercise
Regular physical activity is crucial. Children should aim for at least 60 minutes in 3–5 sessions of moderate-to-high-intensity exercise per day. Both aerobic and resistance exercises are beneficial for reducing intrahepatic fat content and improving metabolic health.
3. Pharmacotherapy
Currently, no medication is approved specifically for MASLD in the children. Vitamin E is the most studied pharmacological agent for pediatric MASLD due to its antioxidant and anti-inflammatory properties, offering some histological improvements. The TONIC Trial (2011) conducted in 173 children with biopsy-proven MASLD, comparing vitamin E (800 IU/day), metformin, and placebo. It showed vitamin E significantly improved liver histology, particularly reducing hepatocellular ballooning, a key feature of steatohepatitis. However, it did not significantly reduce fibrosis or ALT levels compared to placebo. Long-term safety of high-dose vitamin E remains a concern due to potential risks, such as prostatic cancer and haemorrhagic stroke in adults [7]. Drugs such as metformin are not recommended due to insufficient evidence of long-term benefits [8]. Drugs such as GLP-1 analogues (liraglutide and semaglutide) show promising result in adults but lacks pediatric data.
4. Surgical and endoscopic options
Bariatric surgery may be considered for severely obese children >12 years who do not respond to lifestyle and pharmacotherapy interventions. Laparoscopic sleeve gastrectomy and Roux-en-Y gastric bypass have been shown to reduce BMI and improve liver health. Endoscopic treatments, such as intragastric balloons, may be considered in cases where surgery is contraindicated or delayed.
Key updates in Indian guidelines
Shift from NAFLD to MASLD to align with global consensus, emphasizing metabolic dysfunction.
Ultrasound + ALT for initial screening, with transient elastography (FibroScan) for fibrosis and steatosis assessment.
Liver biopsy in selected cases.
Lifestyle modifications with emphasis on Indo-Mediterranean Diet.
Pharmacotherapy and/or endoscopic/surgical techniques for obesity should be considered as adjuncts and should be considered only after a failed adequate trial of lifestyle modifications.
Prevention and community involvement
Prevention starts with early intervention for children at obesity risk. School-based programs that encourage physical activity and healthy eating habits should be conducted regularly. Pediatricians should advocate for lifestyle interventions (including limiting screen time for all the children <2 hr/day) not only at the family level but also within the schools and communities.
Conclusion
MASLD is a growing silent pandemic. Increasing awareness is important for early detection, management, and prevention. Both USG and ALT are recommended for screening, while TE-CAP is advised for monitoring fibrosis and steatosis. Life style modifications remain the primary management. The family therapy is essential to ensure the successful patient outcomes.
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