Metabolic dysfunction-associated steatotic liver disease in children: a practical update based on Indian Society of Pediatric Gastroenterology, Hepatology and Nutrition (ISPGHAN) 2024 guidelines

Article information

Clin Exp Pediatr. 2025;68(7):546-550

Publication date (electronic) : 2025 May 12

doi : https://doi.org/10.3345/cep.2025.00157

Ankit Agrawal, MD, DM ¹

, Arghya Samanta, MD, DM^,²

¹Department of Pediatric Gastroenterology, Post Graduate Institute of Child Health, Noida, Uttar Pradesh, India

²Department of Pediatric Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India

Corresponding author: Arghya Samanta. Department of Pediatric Gastroenterology, SGPGIMS, Raebareli Road, Lucknow-226014, Uttar Pradesh, India Email: arghyasamanta2905@gmail.com

Received 2025 January 19; Revised 2025 April 10; Accepted 2025 April 11.

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).

Table 1.

Important updates and recommendations from the guidelines on the diagnosis and management of pediatric metabolic dysfunction-associated steatotic liver disease published by the Indian Society of Pediatric Gastroenterology, Hepatology, and Nutrition (ISPGHAN), 2024

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.

1. Diet

No specific diet is proven superior. Any hypocaloric diet (low-carbohydrate/low glycemic load/low-fat) promoting weight loss is acceptable [4,5]. Recently, Indo-mediterranean diets have shown promising results in reducing steatosis and ALT levels [6].

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.

Notes

Conflicts of interest

No potential conflict of interest relevant to this article was reported.

Funding

This study received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

References

1. Mann JP, Valenti L, Scorletti E, Byrne CD, Nobili V. Nonalcoholic Fatty liver disease in children. Semin Liver Dis 2018;38:1–13.

2. Elhence A, Bansal B, Gupta H, Anand A, Singh TP, et al. Prevalence of non-alcoholic fatty liver disease in india: a systematic review and meta-analysis. J Clin Exp Hepatol 2022;12:818–29.

3. Schwimmer JB, Dunn W, Norman GJ, Pardee PE, Middleton MS, Kerkar N, et al. SAFETY study: alanine aminotransferase cutoff values are set too high for reliable detection of pediatric chronic liver disease. Gastroenterology 2010;138:1357–64. 1364.e1-2.

4. Ramon-Krauel M, Salsberg SL, Ebbeling CB, Voss SD, Mulkern RV, Apura MM, et al. A low-glycemic-load versus low-fat diet in the treatment of fatty liver in obese children. Child Obes 2013;9:252–60.

5. Goss AM, Dowla S, Pendergrass M, Ashraf A, Bolding M, Morrison S, et al. Effects of a carbohydrate-restricted diet on hepatic lipid content in adolescents with non-alcoholic fatty liver disease: a pilot, randomized trial. Pediatr Obes 2020;15e12630.

6. Deshmukh A, Sood V, Lal BB, Khanna R, Alam S, Sarin SK. Effect of Indo-Mediterranean diet versus calorie-restricted diet in children with non-alcoholic fatty liver disease: a pilot randomized control trial. Pediatr Obes 2024;19e13163.

7. Lavine JE, Schwimmer JB, Van Natta ML, Molleston JP, Murray KF, Rosenthal P, et al. Effect of vitamin E or metformin for treatment of nonalcoholic fatty liver disease in children and adolescents: the TONIC randomized controlled trial. JAMA 2011;305:1659–68.

8. Gkiourtzis N, Michou P, Moutafi M, Glava A, Cheirakis K, Christakopoulos A, et al. The benefit of metformin in the treatment of pediatric non-alcoholic fatty liver disease: a systematic review and meta-analysis of randomized controlled trials. Eur J Pediatr 2023;182:4795–806.

9. Vos MB, Abrams SH, Barlow SE, Caprio S, Daniels SR, Kohli R, et al. NASPGHAN clinical practice guideline for the diagnosis and treatment of nonalcoholic fatty liver disease in children: recommendations from the Expert Committee on NAFLD (ECON) and the North American Society of Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN). J Pediatr Gastroenterol Nutr 2017;64:319–34.

10. Vajro P, Lenta S, Socha P, Dhawan A, McKiernan P, Baumann U, et al. Diagnosis of nonalcoholic fatty liver disease in children and adolescents: position paper of the ESPGHAN Hepatology Committee. J Pediatr Gastroenterol Nutr 2012;54:700–13.

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Table 1.

	ISPGHAN guidelines 2024	NASPGHAN guidelines 2017 [9]	ESPGHAN position paper 2012 [10]
Change in terminology	MASLD	NAFLD	NAFLD
Screening tool	USG and ALT levels	ALT	USG and ALT levels
Population to be screened	Screening for MASLD should be considered in all obese children (BMI >95th percentile) and in all overweight children (BMI ≥85th and <95th) with additional risk factors–prediabetes/diabetes, dyslipidemia, waist circumference greater than 70th percentile, hypertension, positive family history of metabolic syndrome, obstructive sleep apnea, and hypopituitarism	Screening should be considered beginning between ages 9–11 years for all obese children (BMI ≥95th percentile) and for overweight children (BMI ≥85th and < 94th percentile) with additional risk factors (central adiposity, insulin resistance, prediabetes or diabetes, dyslipidemia, sleep apnea or family history of NAFLD/NASH).	No clear-cut screening recommendations
	Consider screening of siblings of patients with MASLD in the presence of risk factors (overweight/obesity, prediabetes/diabetes, and/or dyslipidemia)	Earlier screening can be considered in younger patients with risk factors such as severe obesity, family history of NAFLD/NASH or hypopituitarism.	At Risk population defined – obese (>95th percentile) and overweight (sex and age specific BMI >85th percentile), Hispanic origin, children from families with insulin resistance, obesity, type II DM and NAFLD, children with obstructive sleep apnea
		Consider screening of siblings and parents of children with NAFLD if they have known risk factors for NAFLD (obesity, Hispanic ethnicity, insulin resistance, prediabetes, diabetes, dyslipidemia)
Diet	Any hypocaloric diet (low-carbohydrate/low fat/low sugar) or mediterranean diet	Reduction of sugar-sweetened beverages recommended	No recommendation
Exercise	Exercise (aerobic or resistance or a combination of both) is an effective measure for weight loss and reduction of intrahepatic fat content	Moderate-to-high intensity physical activity and limiting screen time activities to < 2 hours per day is recommended for all children including those with NAFLD	No recommendation
Exercise	Moderate-to-high-intensity exercise in 3–5 sessions for a total of 60 min/day is recommended for children and adolescents with MASLD		No recommendation
Liver biopsy	Liver biopsy in overweight/obese children with suspected MASLD is recommended: In younger children <8 yr, and/or if there is a high index of suspicion for advanced liver disease, and/or if an alternative diagnosis is considered.	Liver biopsy should be considered for the assessment of NAFLD in children who have increased risk of NASH and/or advanced fibrosis. Potential clinical signs of increased risk of fibrosis in children with NASH may include higher ALT (>80 U/L), splenomegaly, and AST/ALT >1. Known clinical risk factors for NASH and advanced fibrosis include panhypopituitarism and type 2 diabetes	To exclude other treatable disease
			In cases of clinically suspected advanced liver disease
			Before pharmacological/surgical treatment
Pharmacological	Pharmacotherapy for weight loss may be considered as an adjunct to lifestyle interventions and started only after a failed trial of life style modifications for 6 months	No medications recommended for NAFLD due to lack of benefit in children	Limited data for pharmacotherapy in children, lifestyle interventions preferred
Bariatric surgery	Children (>12 yr) who had a failure of an appropriate trial of intense lifestyle modifications and pharmacotherapy for at least 6 months and one of the following: class 2 obesity with steatosis/steatohepatitis with significant comorbidities. class 3 obesity with steatosis/steatohepatitis with or without comorbidities	Bariatric surgery is not recommended as a specific therapy for NAFLD. It may be considered for selected adolescents with BMI ≥35 kg/m², who have noncirrhotic NAFLD and other serious comorbidities (e.g., T2DM, severe sleep apnea, idiopathic intracranial hypertension) that are likely to improve with weight loss surgery	No recommendation
Endoscopic intragastric ballon	When bariatric surgery is contraindicated or delayed	No recommendation	No recommendation

ISPGHAN, Indian society of pediatric gastroenterology hepatology and nutrition; NASPGHAN, North American society for pediatric gastroenterology hepatology and nutrition; ESPGHAN, European society of pediatric gastroenterology hepatology and nutrition; MASLD, metabolic dysfunction-associated steatotic liver disease; NAFLD, nonalcoholic fatty liver disease; USG, ultrasonography; ALT, alanine aminotransferase; BMI, body mass index; NASH, nonalcoholic steatohepatitis; AST, aspartate aminotransferase; T2DM, type 2 diabetes mellitus.