Paediatric metabolic dysfunction-associated steatotic liver disease (MASLD): a growing health concern in the age of childhood obesity

Abstract

Metabolic dysfunction-associated steatotic liver disease (MASLD), previously called non-alcoholic fatty liver disease, has emerged as the most common chronic liver disease in children and adolescents. This is happening in parallel to the global rise in paediatric obesity. Prevalence estimates are 13% in the general population and 47% among children with obesity, with higher rates observed in certain ethnic groups and in males. MASLD is often silent in early stages but may progress to steatohepatitis, fibrosis, cirrhosis and liver failure in a subset of patients. The pathophysiology of MASLD is multifactorial, involving excess calorie intake, insulin resistance and altered lipid metabolism. Genetic variants, particularly in PNPLA3, TM6SF2, GCKR, MBOAT7 and HSD17B13 influence disease susceptibility and disease severity, with some increasing the risk while others exhibiting a protective effect. The gut-liver axis, through mechanisms like increased intestinal permeability and dysbiosis, also contributes to hepatic fat accumulation and inflammation. The natural history of MASLD in children is variable. Some children may remain in remission while others may progress to advanced liver disease. Management is centred on lifestyle modification. A balanced, calorie-controlled diet, particularly a Mediterranean diet, has been shown to be beneficial in children and adolescents with MASLD, along with regular physical activity. Weight loss has been associated with histological improvement. Role of pharmacotherapy remains limited in the management of MASLD. Interventions like vitamin E, omega-3 fatty acids and GLP-1 receptor agonists are being explored in clinical trials with positive results. This narrative review is timely and relevant, as the growing burden of MASLD in children and adolescents calls for greater awareness and updated knowledge among clinicians and researchers. Despite notable progress in understanding the condition, important gaps remain regarding its natural history, early identification, and effective therapeutic options in the younger population. By bringing together current evidence and highlighting these areas of uncertainty, this review aims to support ongoing research and inform more age-appropriate approaches to care.

Key messages.

• Metabolic dysfunction-associated steatotic liver disease is the most common chronic liver disease in children and adolescents, with rising prevalence driven by increasing rates of obesity and metabolic syndrome.

• Pathophysiology is multifactorial, involving insulin resistance, genetic predisposition, inflammation and gut-liver axis dysregulation.

• The condition is often asymptomatic in early stages, making early diagnosis challenging but essential to prevent progression.

• Lifestyle interventions are the cornerstone of treatment, including a Mediterranean diet or a low-calorie free-sugar diet and regular physical activity.

• Pharmacotherapy options remain limited in children and adolescents.

Introduction

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common liver disease in the world.¹ MASLD is an umbrella term which comprises isolated hepatic steatosis (metabolic dysfunction-associated steatotic liver), metabolic dysfunction-associated steatohepatitis (MASH), fibrosis and cirrhosis (figure 1).² MASLD is characterised by steatosis affecting more than 5% of hepatocytes, while MASH is defined histologically by hepatocellular ballooning and lobular inflammation.^{2 3} The estimated pooled prevalence of MASLD is 38% among adults.⁴ The corresponding figures are 13% in general population and 47% in obese population, for children and adolescents.⁵

Figure 1. Progression of MASLD: From simple steatosis to advanced fibrosis, cirrhosis and hepatocellular carcinoma (HCC). MASH, metabolic dysfunction-associated steatohepatitis; MASLD, metabolic dysfunction-associated steatotic liver disease.

In 2023, the nomenclature changed from non-alcoholic fatty liver disease (NAFLD) to MASLD following a multisociety Delphi consensus, aiming to emphasise the underlying aetiology rather than what the condition is not—‘non-alcoholic’.^{6 7} The general term ‘fatty liver disease’ has been replaced by the term ‘steatotic liver disease’. From an initial list of 140 cardiometabolic risk factors, the Delphi consensus identified five key categories to be included in the definition of MASLD, each encompassing multiple related components. In the presence of hepatic steatosis without any associated metabolic risk factors, it would be considered as cryptogenic steatotic liver disease.⁶

The new definition of MASLD is the presence of excess triglyceride storage in the liver in the presence of at least one of the five cardiometabolic risk factors and no other discernible cause.² These cardiometabolic factors include overweight/obesity, elevated triglyceride levels, hypertension or elevated blood pressure, type 2 diabetes or elevated blood sugar levels, and low high-density lipoprotein (HDL) levels.⁶ The cut-off values for the paediatric and adult population are described in table 1.

Table 1. Cardiometabolic criteria for the diagnosis of MASLD.

At least 1 out of 5
Adult criteria	Paediatric criteria
BMI ≥25 kg/m2 (23 Asia) OR WC >94 cm (M) 80 cm (F) OR ethnically adjusted	BMI ≥85th percentile for age/sex (BMI z score ≥+1) OR WC >95th percentile OR ethnicity adjusted
Fasting serum glucose ≥5.6 mmol/L (100 mg/dL) OR 2-hour postload glucose levels ≥7.8 mmol/L (≥140 mg/dL) OR HbA1c ≥5.7% (39 mmol/L) OR type 2 diabetes OR treatment for type 2 diabetes.	Fasting serum glucose ≥5.6 mmol/L(≥100 mg/dL) OR serum glucose ≥11.1 mmol/L (≥200 mg/dL) OR 2-hour postload glucose levels ≥7.8 mmol (140 mg/dL) OR HbA1c ≥5.7% (39 mmol/L) OR already diagnosed/treated type 2 diabetes OR treatment for type 2 diabetes
BP ≥130/85 mm Hg OR specific antihypertensive drug treatment	BP age <13 years, BP ≥95th percentile OR ≥130/80 mm Hg (whichever is lower); age ≥13 years, 130/85 mm Hg OR specific antihypertensive drug treatment
Plasma triglycerides ≥1.70 mmol/L (150 mg/dL) OR lipid-lowering treatment	Plasma triglycerides <10 years, ≥1.15 mmol/L (≥100 mg/dL); age ≥10 years, 1.70 mmol/L (≥150 mg/dL) OR lipid-lowering treatment
Plasma HDL-cholesterol ≤1.0 mmol/L (40 mg/dL) (M) and ≤1.3 mmol/L (50 mg/dL) (F) OR lipid-lowering treatment	Plasma HDL-cholesterol less than or equal to 1.0 mmol/L OR lipid-lowering treatment

BMI, body mass index; BP, blood pressure; F, female; HbA1c, glycated hemoglobin; HDL, high-density lipoprotein; M, male; MASLD, metabolic dysfunction-associated steatotic liver disease; WC, waist circumference.

Studies in recent decades have provided with a reasonable understanding of the natural history, early identification, and optimal management of MASLD in paediatric populations. The available information is still evolving and certain aspects need more clarity as well. This review aims to enhance awareness and support the development of more targeted and age-appropriate clinical approaches, and inform future research directions by synthesising the current evidence available on this topic.

This narrative review involved a structured search of PubMed, Scopus, and Web of Science for relevant literature up to the most recent year. Keywords included “MASLD”, “NAFLD”, “paediatric fatty liver”, “genetic variants”, “gut-liver axis” and “management”. Priority was given to original studies, randomised controlled trials, systematic reviews, and consensus statements. Additional articles were identified through manual screening of reference lists to ensure comprehensive coverage of the topic.

Epidemiology

A meta-analysis (2016) that included studies published between 1990 and 2015 reported that the global pooled prevalence of MASLD in adults was 25%. A follow-up study done by the same group of researchers reported that the figure rose to 38% between 2015 and 2019.^{4 8}

A meta-analysis of 76 studies published in 2015 conducted among children showed that the pooled prevalence was 7.6% and 34.2% in the general population and clinical obese population, respectively.⁹ The highest prevalence of MASLD in the general paediatric population was found to be in South America (25.1%), followed by Oceania (10%).⁹ In the clinical obese population, the highest prevalence was found to be in Asia, with 62.3% of obese children having MASLD.⁹ More recent evidence from a 2024 meta-analysis estimated the prevalence to be 13% in the general paediatric population and 47% among children and adolescents with obesity, suggesting a substantial increase in disease burden over time.⁵ Another study reported an annual increase of 1.35% in MASLD among children and adolescents from 1990 to 2017.¹⁰ This increase was found to be higher in boys (1.36%) than in girls (1.35%).¹⁰ The annual increase was found to be the highest in North Africa and the Middle East region (EAPC=2.05%) and the lowest in Eastern Sub-Saharan Africa (EAPC=0.62%).¹⁰ The global prevalence of MASLD in adolescents increased over 25%, from 3.73% in 1990 to 4.71% in 2019, in adolescents.¹¹ South America and North America had the largest relative increases in adolescent MASLD from 1990 to 2019.¹¹ In the same study, it was seen that increased obesity, but not type 2 diabetes, was correlated to a rising prevalence of MASLD in adolescents globally.¹¹ A trend analysis study (2015 to 2020) showed an estimated global prevalence of MASLD in children with obesity to be 26%. The study reported a higher prevalence among males (29.4%) compared with females (22.6%).^{12 13} A recent meta-analysis (52 studies, 15 53 683 participants) concluded that 2.6%, 10.4% and 41.2% children and adolescents with normal weight, overweight and obese, respectively, had MASLD.⁸ This meta-analysis confirms the dose-response effect of body mass index (BMI) on the prevalence of MASLD during childhood and adolescence.¹⁴

A recent systematic review and meta-analysis done in India (62 studies) sheds light on the relevance of this problem in the subcontinent.¹⁵ The meta-analysis reported a pooled prevalence of 35.4% for MASLD among the paediatric population in India. The pooled estimate was 12.4% and 63.4% separately for non-obese and obese children, respectively.¹⁵ The risk appears to be higher among the Indian population compared with the global population.

Natural history of MASLD

The natural history of MASLD in adults is well established. However, the progression of MASLD in children is still evolving with very few longitudinal studies available. MASLD in children is dynamic and may involve phases of both development and remission.¹⁶ MASLD is most commonly diagnosed during puberty and adolescence. However, the true onset of the disease may occur earlier and remains unclear.¹⁷

A prospective study conducted in Taiwan tracking obese children aged 9–13 years over 2 years found that while 19.5% had MASLD at baseline, 7.6% of those initially unaffected developed it within a year. In the study, it was noted that an increase in BMI z-score independently predicted MASLD onset, while a decrease predicted remission.¹⁶

Long-term follow-up data support persistence of paediatric/adolescent MASLD into adulthood. In a retrospective cohort study by Feldstein et al, 66 children with biopsy-proven MASLD were followed up to 20 years.¹⁸ The authors concluded that paediatric MASLD could progress to severe liver outcomes, including cirrhosis, liver transplantation and death.¹⁸ A subset of patients developed type 2 diabetes and fibrosis progression. Two patients underwent transplantation, and the standardised mortality ratio was significantly higher in children with MASLD than the general population.¹⁸ These findings suggest that MASLD in childhood is not uniformly benign and may persist or progress over time, particularly in the presence of ongoing metabolic risk factors such as obesity. These associations highlight the importance of early identification and intervention.

Pathophysiology

MASLD is characterised by excessive fat accumulation in the hepatocytes.² Various risk factors have been associated with MASLD, obesity and insulin resistance being the most common.¹⁹ Day and James presented a ‘two-hit’ hypothesis where they suggested that, in addition to the first hit, which is hepatic steatosis, another factor(s) is required to develop steatohepatitis (second hit), oxidative stress leading to lipid peroxidation.²⁰ In 2010, a multiple parallel hit hypothesis was proposed suggesting that there may be multiple factors acting in parallel.^{21 22} This theory suggests that inflammatory mediators from various tissues (especially from gut and adipose tissues) play a major role in the development of a cascade of inflammation, fibrosis and tumour formation in the hepatocytes, especially the ones from gut and adipose tissue. Major contributing factors include excess calories, insulin resistance, derangements in fatty acid (FA) metabolism, genetic factors, and gut microbiome dysbiosis (figure 2).²³ Additional contributing factors include hormonal influences, dietary composition, physical inactivity, sleep disturbances, adipokine imbalance, oxidative stress and environmental or medication-related exposures.²⁴

Figure 2. Key pathophysiological mechanisms driving MASLD development and progression. ChREBP, carbohydrate-responsive element-binding protein; JNK, c-Jun N-terminal kinase; MASLD, metabolic dysfunction-associated steatotic liver disease; NF-kB, nuclear factor kappa B; SREBP-1c, sterol regulatory element-binding protein 1c; TG, triglyceride; TGF-β, transforming growth factor beta.

Excess calorie intake and insulin resistance

MASLD typically begins with excess calorie intake, which drives hepatic steatosis through an imbalance between triglyceride deposition and disposal in the hepatocytes. De-novo lipogenesis (DNL) is the pathway where FAs are synthesised from non-lipid sources such as carbohydrates. Excess caloric intake in the form of carbohydrates like monosaccharides (glucose and fructose) and disaccharides (sucrose) can lead to increased blood glucose levels, which over a period of time leads to skeletal muscle insulin resistance.^{25 26} This leads to excess glucose in the blood being diverted to the liver, where it enters the DNL pathway, producing triglycerides.^{27 28}

Fructose is a monosaccharide which is found in fruits, honey and is a component of table sugar (sucrose). It is present in the form of high fructose corn syrup in the modern diet including sweetened fruit juices and carbonated drinks. Fructose has been shown to have a significant association with MASLD, particularly in children who are overweight and obese.29,31 Fructose is almost exclusively metabolised in the liver, where it bypasses key regulatory steps of glycolysis, leading to increased triglyceride production via DNL pathway.^{31 32} Additionally, fructose metabolism promotes ATP depletion and uric acid generation, contributing to oxidative stress, insulin resistance and hepatic fat accumulation.^{31 32}

Excess calorie intake and obesity can lead to insulin resistance in the adipose tissue by promoting adipocyte hypertrophy, an increase in inflammatory cytokine release, and impairing insulin signalling pathways.³³ Under normal circumstances, lipolysis is tightly regulated. Excess calories are usually stored in the adipocytes as triglycerides. Adipose tissue breaks down stored fat in response to energy needs (fasting state), and insulin suppresses this process in the fed state. In MASLD, adipose tissue insulin resistance leads to dysregulated lipolysis, flooding the liver with excess free FAs (FFAs).³⁴ Circulating FFAs released from visceral adipose tissue enter the liver through the portal vein and increase the intrahepatic triglycerides, even in individuals without obesity.³⁵

Derangements in fatty acid metabolism

Altered lipid metabolism is a major factor contributing to the development and progression of MASLD. There is an upregulation of key enzymes integral to the DNL pathway in patients with MASLD.²⁸ Sterol regulatory element-binding protein 1c (SREBP1c), one of the master regulators of the DNL pathway, activated by insulin has been shown to be significantly higher in patients with MASLD compared with those who do not have the same.^{28 36} Carbohydrate-responsive element binding protein (ChREBP), another transcription factor, is upregulated in patients with MASLD.³² This protein plays a key role in enhancing fat synthesis via DNL and is produced in response to high glucose levels.³⁶ Several studies have shown how an increased intake of fructose has been associated with an increased prevalence of MASLD, and fructose is an effective activator of ChREBP.36,38 Thus, activation of SREBP1c and ChREBP enhances the DNL pathway, resulting in excess production and accumulation of triglycerides in the hepatocytes, leading to steatosis. Persistent triglyceride accumulation and lipotoxicity can lead to oxidative stress and release of pro-inflammatory cytokines, which activate Kupffer cells, triggering inflammation. The resulting inflammatory mediators and cellular injury activate hepatic stellate cells, leading to fibrogenic responses, contributing to hepatic fibrosis.³⁹

Genetic factors

Genetic factors play an important role in the development and progression of MASLD and fibrosis.⁴⁰ Several key risk variants have been identified such as patatin-like phospholipase domain-containing protein 3 (PNPLA3), transmembrane 6 superfamily member 2 (TM6SF2), membrane-bound-O-acyltransferase domain containing 7 (MBOAT7) and glucokinase regulatory protein (GCKR).40,43 In recent years, a protective variant has also been identified, hydroxysteroid 17-β dehydrogenase 13 (HSD17B13).^{44 45}

The PNPLA3 rs738409 C>G polymorphism is the most significantly associated genetic component with MASLD, with studies reporting 2–3 fold increased risk of steatosis and fibrosis in carriers of the G allele.⁴⁴ PNPLA3 facilitates hydrolysis of triglycerides within lipid droplets into FFAs. The I148M (rs738409) variant reduces the enzyme activity and promotes accumulation of triglycerides on lipid droplets in the hepatocytes.⁴⁶ TM6SF2 rs5854926 C>T polymorphism results in impaired VLDL assembly and the export of VLDL, leading to triglyceride accumulation, promoting hepatic steatosis. This variant has been associated with a 1.5-to-two-fold increase in the risk of hepatic steatosis.⁴⁷ MBOAT7 gene plays a crucial role in conversion of arachidonic acid to phosphatidyl inositols with the help of lysophosphatidyl inositol acyltransferase 1. The rs641738 C>T polymorphism in MBOAT7 reduces the expression of this gene in hepatocytes and immune cells, leading to elevation in free arachidonic acid, resulting in increased lipid accumulation and inflammation.⁴⁸ Two variants in the gene GCKR have been identified, rs1260326 C>T and rs780094 C>T, which have been shown to enhance lobular inflammation in patients with MASH and T2DM.⁴⁹ The risk variants have been shown to exacerbate mitochondrial dysfunction in MASLD by increasing glycolysis and lipogenesis.⁴⁹ The exact mechanism of HSD17B13 gene is not completely understood. This gene is expressed in the membranes surrounding the lipid droplets.⁵⁰ The rs72613567 T>TA variant promotes adipose triglyceride lipase-dependent lipolysis which protects against MASLD.⁵¹ These mechanisms are illustrated in figure 3.

Figure 3. Genetic factors and pathways influencing MASLD susceptibility and severity. ATGL, adipose triglyceride lipase; MASLD, metabolic dysfunction-associated steatotic liver disease; VLDL, very low-density lipoprotein.

The complex interplay between genetic and environmental factors, particularly obesity, contributes to the heterogeneity of the MASLD presentation.⁵² Specific genetic variants can increase susceptibility to hepatic steatosis and inflammation, but environmental influences such as diet quality, physical activity and gut microbiota may determine whether and how these genetic risks manifest clinically.⁵³ This interaction may partly explain why some individuals develop MASLD earlier or progress more rapidly, while others remain relatively protected despite similar lifestyle exposures.

Gut microbial dysbiosis

There is a complex interaction between gut microbiota dysbiosis, insulin resistance and inflammation which is influenced by diet, host genetics and gut-liver axis signalling.⁵⁴ In children, dysbiosis is characterised more by reduced microbial diversity, depletion of beneficial butyrate-producing taxa (eg, Faecalibacterium, Coprococcus) and expansion of Proteobacteria, and less by a consistent shift in the Firmicutes/Bacteroidetes (F/B) ratio.⁵⁵ Although many studies report an increased F/B ratio in obesity and MASLD, findings are inconsistent across paediatric populations.

Gut microbiome affects MASLD through multiple mechanisms. Fermentation of complex carbohydrates produces short chain FAs (SCFAs). These SCFAs modulate metabolism and inflammation, via histone deacetylase inhibition, which is one such mechanisms.⁵⁶ Besides SCFAs, there are other metabolites that play a key role. Altered bile acid metabolism affects Farnesoid X Receptor and Takeda G protein-coupled receptor 5 (TGR5) signalling, promoting hepatic inflammation, insulin resistance and fibrosis.⁵⁷ Additionally, altered choline metabolism leads to reduced VLDL export from the liver thereby promoting hepatic steatosis.^{58 59}

Intestinal damage can occur due to bacterial ethanol production. Other mechanisms responsible for increased gut permeability include nutrient (such as diets high in carbohydrates and high saturated fats) and microbial effects.⁶⁰ Increased gut permeability allows endotoxins such as lipopolysaccharides to translocate from the gut into the liver, triggering inflammation via toll-like receptor signalling and inflammasomes.⁶¹ While normal inflammasome function may protect the liver, its dysfunction promotes inflammation, insulin resistance and fat accumulation, contributing to genesis and progression of MASLD.⁶¹ Overall, paediatric MASLD is driven by microbial imbalance, barrier dysfunction and metabolite-mediated liver injury beyond SCFAs alone.

Clinical features

MASLD in children and adolescents often has an asymptomatic presentation in the early stages. MASLD is often identified incidentally through elevated liver enzymes, especially alanine aminotransferase (ALT) or imaging studies showing hepatic steatosis.⁶² They are often diagnosed with MASLD on screening children with obesity, diabetes, hypertension or dyslipidaemia, which are the cardiometabolic risk factors.⁶³ Acanthosis nigricans, irregular menstrual cycle or daytime sleepiness due to obstructive sleep apnoea may also be the reasons for screening.⁶³ Symptoms, if present, are non-specific. Some of the symptoms may include right upper quadrant or diffuse abdominal discomfort and fatigue.⁶² Physical examination may reveal hepatomegaly in a subset of patients with MASLD.⁶²

Diagnosis of MASLD

The clinical manifestations in MASLD are often subtle, which makes the diagnosis of this disease more challenging. The core cardiometabolic risk factors used to establish the diagnosis of MASLD—such as overweight/obesity, hypertension, hyperglycaemia and dyslipidaemia—remain consistent across age groups.⁶ The paediatric guidelines emphasise the age-appropriate cut-off values for the cardiometabolic risk factors for the diagnosis of MASLD as given in table 1. The current multisociety guidelines highlight the presence of hepatic steatosis in imaging accompanied by at least one of the five cardiometabolic criteria to support the diagnosis of MASLD.⁶

In addition, paediatric guidelines also emphasise the importance of ruling out secondary causes of hepatic steatosis, such as genetic, metabolic or infectious liver diseases, which may be prevalent in younger age groups.⁶⁴ These include Wilson’s disease, alpha-1 antitrypsin deficiency, cystic fibrosis, coeliac disease, thyroid dysfunction, glycogen storage disorders and mitochondrial hepatopathies.⁶⁴ The paediatric guidelines recommend performing a first-line investigation for steatosis to rule out these causes.⁶⁴ Failing to identify these conditions early leads to misclassification, inappropriate management and missed opportunities for disease-specific treatments.

Expert consensus highlights the need to evaluate for clinical ‘red flags’ in the diagnostic process, ensuring accurate classification and avoiding misdiagnosis to aid in distinguishing MASLD from secondary causes.⁶⁴ The ‘red flags’ include—age under 8 years, developmental delay, synthetic dysfunction, BMI z score <1, splenomegaly and history suggestive of another aetiology.⁶⁴ Age less than 8 years is considered a red flag as an early presentation raises concern for alternative or coexisting liver diseases such as Wilson’s disease or congenital liver disease, warranting more extensive evaluation⁶⁴

Management of MASLD

The management of MASLD in the paediatric population is multifaceted (figure 4) and aims to reduce hepatic steatosis, halt disease progression, and address associated metabolic dysfunctions. Lifestyle modifications remain the mainstay of treatment for this population, with pharmacotherapy reserved for select cases.

Figure 4. Overview of current and emerging strategies for the management of MASLD in children and adolescents. DHA, docosahexaenoic acid; MASLD, metabolic dysfunction-associated steatotic liver disease; vit, vitamin.

Dietary management

Dietary guidelines for the management of paediatric and adolescent MASLD are still evolving. A growing body of evidence supports targeted dietary interventions to improve hepatic and metabolic outcomes in this population. Among these interventions, the Mediterranean diet and free-sugar-restricted diet appear to be the most promising options according to the current guidelines.^{2 65 66} The Mediterranean diet is characterised by a high intake of vegetables, fruits, legumes, whole grains, nuts, olive oil and moderate consumption of fish and poultry. Therapy with Mediterranean diet has been associated with improvements in liver enzymes and hepatic steatosis.⁶⁷ A recent meta-analysis in paediatric interventional studies reported moderate reductions in serum ALT, aspartate aminotransferase (AST) and gamma-glutamyl transferase (GGT) levels following adherence to the Mediterranean diet.⁶⁷ The same study also reported minimal changes were observed in weight, lipid profile, or insulin sensitivity. This suggests that a Mediterranean diet can be beneficial in adolescents with MASLD, independent of weight loss.⁶⁷

A randomised controlled trial (RCT) done in India compared the Indo-Mediterranean diet (IMD) with a calorie-restricted diet over 6 months in adolescents with MASLD. The IMD group experienced significantly greater reductions in hepatic fat, body weight, and BMI, along with improvements in lipid profile and insulin resistance.⁶⁸ Similarly, another RCT in Turkey showed that children on a Mediterranean diet had greater reductions in AST and high-sensitive C reactive protein, and increased antioxidant markers such as paraoxonase-1 and glutathione peroxidase, compared with those on a low-fat diet.⁶⁹

Free-sugar restriction has shown promising results. An RCT published in JAMA demonstrated that reducing dietary free sugars to less than 3% of total energy intake over 8 weeks led to a 6% reduction in hepatic steatosis and significant improvement in ALT among obese adolescent boys.⁷⁰ Another study confirmed that sugar restriction led to decreased DNL, which correlated with improvements in hepatic fat content, ALT and insulin sensitivity.⁷¹

A recent international consensus on metabolic dysfunction-associated fatty liver disease emphasises the importance of achieving and maintaining a healthy body weight through adherence to a balanced diet that adjusts energy intake and expenditure. It recommends personalised nutritional interventions – such as calorie-restricted diets, high protein diets, low carbohydrate diets (<40% or <60 g/day of carbohydrates), and intermittent energy restriction, which is primarily for adults, under professional dietary supervision. The consensus also advocates for a diet emphasising whole grains over refined grains, plant-based protein sources, regular intake of fish and seafood, low-fat or fat-free dairy, lean, unprocessed meats when consumed. This consensus encourages a Mediterranean diet in paediatric MASLD.⁷² The evidence related to MASLD in children and adolescents is still evolving, highlighting the need for long-term, diverse and culturally sensitive studies. Such studies will definitely help develop effective dietary guidelines for this population.

Physical activity

Emerging evidence suggests that both aerobic and resistance exercise offer modest but clinically beneficial effects in children with MASLD. These include small reductions in hepatic steatosis and improvements in liver enzymes.^{73 74} In a RCT involving adolescent boys with obesity, 3 months of supervised aerobic or resistance training performed three times per week resulted in ~1% absolute reductions in hepatic fat content, as assessed by MRI.⁷⁴ Similarly, in children aged 8–12 years, the combinations of high-intensity aerobic exercise three times weekly with a structured lifestyle programme led to a comparable ~1% reduction in hepatic steatosis.⁷⁵ Current evidence does not demonstrate clear superiority of one form of exercise over the other, and overall exercise volume and adherence appear to be more important determinants of benefit in young patients with MASLD. The AASLD (American Association for the Study of Liver Diseases) guidelines appear to be consistent with this conclusion.⁶⁶ AASLD guidelines recommend that all children, regardless of weight status, should engage in daily moderate-to-vigorous physical activity through age-appropriate activities such as free play, school-based exercise, and organised sports, in line with current clinical practice recommendations.⁶⁶ In addition, the Indian Society of Paediatric Gastroenterology, Hepatology and Nutrition advises that schools should ensure at least 60 min of structured physical activity per day, reinforcing the role of institutional and environmental support in MASLD prevention and management.⁶³ We can conclude that a combination of dietary and physical activity interventions should be the mainstay in the management of paediatric/adolescent MASLD.

Pharmacotherapy

Pharmacotherapy for MASLD or MASH in the paediatric population is an evolving area, with no currently approved drugs specifically for this population, as highlighted by the AASLD guidelines.⁶⁶ These guidelines also caution against the use of herbal supplements due to unproven efficacy and potential hepatotoxicity. They also suggest that the medications approved for obesity or type 2 diabetes in children aged 12 and older, particularly GLP-1 receptor agonists, may be considered in eligible patients in accordance with approved age-specific indications.⁶⁶ Notably, Semaglutide was Food and Drug Administration (FDA)-approved in 2022 for adolescents ≥12 years with obesity, once weekly at a dosage of 2.4 mg.⁶⁶ The Indian consensus guidelines provide advice on pharmacotherapy for MASLD in children >12 years.⁶³ The guideline advises that pharmacotherapy for MASLD in adolescents should be attempted only after a failure of 6-month long exclusive lifestyle intervention.⁶³

Vitamin E has shown potential benefits in MASLD.⁶⁶ Vitamin E is not FDA-approved for MASLD/MASH and may be considered only in biopsy-proven MASH in children.⁶⁶ Tocotrienol-rich fraction vitamin E showed antioxidant and anti-inflammatory benefits in a recent RCT for MASLD.⁷⁶ In addition, the RCT reported reduction in liver enzymes and reduced DNA damage in obese children with MASLD.⁷⁶ In another study, a combination of hydroxytyrosol, a phenolic compound and vitamin E improved steatosis and systemic inflammation in children with MASLD.⁷⁷ A recent RCT reported that a mix of docosahexaenoic acid, choline and vitamin E reduced severe steatosis and improved liver enzymes in children with MASH.⁷⁸ Zahmatkesh et al reported that Orlistat, a lipase inhibitor, demonstrated improvements in liver enzymes, steatosis, low-denisty lipoprotein (LDL) and HDL in adolescents with MASLD compared with placebo in a recent RCT.⁷⁹ Vos et al reported that losartan, an angiotensin II receptor blocker, had no significant effect on ALT in children with MASLD in another RCT.⁸⁰ Famouri reported that probiotic supplementation showed efficacy in reducing liver enzymes along with reduction in steatosis in obese children with MASLD.⁸¹ These findings suggest that we may identify effective pharmacological strategies that could be adjuncts to lifestyle modifications for managing paediatric MASLD in the near future.

Conclusions

MASLD has become a leading cause of chronic liver disease in children and adolescents and is closely linked to the growing prevalence of obesity and metabolic dysfunction in this age group. A subset of patients with MASLD may progress to MASH and advanced fibrosis, including cirrhosis. Emerging data suggest that higher BMI during childhood strongly influences both the onset and potential remission of MASLD, emphasising the importance of early intervention. Lifestyle modification remains the cornerstone of management, with a focus on balanced dietary patterns, increased physical activity and sustained weight control. Individual responses to dietary changes among children and adolescents with MASLD may partly depend on their genetic makeup. Emerging data strongly suggest that gene-environment interactions are associated with the manifestation of MASLD and could modify the effects of certain nutrients or dietary patterns. Research on paediatric MASLD is still limited. Early diagnosis, individualised risk assessment and developmentally appropriate management strategies are essential to tackle the growing burden of paediatric and adolescent MASLD. Multidisciplinary approaches and public health efforts are urgently needed to improve long-term outcomes for children and adolescents with MASLD.