What is the most recent information on managing MASLD/MASH in pediatric and adolescent patients?

Introduction
Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly referred to as nonalcoholic fatty liver disease (NAFLD), is the most common pediatric liver disease, affecting approximately 10% of children.1 It is estimated that about 5% to 7% of children have the severe form of MASLD known as metabolic dysfunction-associated steatohepatitis (MASH), previously referred to as nonalcoholic steatohepatitis (NASH).2 In children, MASLD is defined by hepatic steatosis (through imaging or biopsy) along with at least 1 metabolic risk factor (overweight/obesity or visceral adiposity, impaired glucose tolerance, low high-density lipoprotein [HDL], elevated blood pressure, or high triglycerides).3,4 MASH is a progressive form of MASLD in which hepatocellular inflammation and injury eventually leads to fibrosis, cirrhosis, hepatocellular carcinoma, and other severe complications.

In both adults and children, lifestyle modifications are the primary treatment for MASLD/MASH, and pharmacologic treatment options are limited.4,5 In 2023, the American Association for the Study of Liver Diseases (AASLD) stated that some medications may be considered for off-label use in MASH (eg, vitamin E, pioglitazone, glucagon-like peptide-1 [GLP-1] receptor agonists), but notes that none of these therapies have specifically demonstrated an antifibrotic benefit.5 There are now 2 FDA-approved agents for MASH in adults – semaglutide and resmetirom – but neither has specific approval for MASH in pediatric patients.4,6

Guideline recommendations
The AASLD published guidelines on MASLD for pediatric patients in 2025.4 At the time of writing (literature search through March 6, 2024), the guidelines recommended lifestyle interventions as summarized in Table 1.

Table 1. AASLD lifestyle key points for pediatric patients with MASLD/MASH.4
Nutrition and exercise are the treatment foundation for MASLD in children.
Isolated reduction of added sugars has demonstrated significant improvement in steatosis and liver enzymes in children with MASLD.
Mediterranean diets may benefit children for long-term cardiovascular risk reduction.
Additional dietary approaches may include:
  • Reducing ultra-processed foods
  • Age-appropriate portion sizes
  • Balanced diets
  • Increased fruit and vegetable intake
Both aerobic and resistance exercise may be beneficial for modest reductions in liver fat, ALT, and AST levels.
  • There is not a preferred form of exercise.
  • All children should engage in daily moderate-to-vigorous age-appropriate activity.
Abbreviations: ALT, alanine aminotransferase; AST, aspartate aminotransferase; MASLD=metabolic dysfunction-associated steatotic liver disease.

The AASLD guidelines highlighted the need for pediatric trials evaluating pharmacotherapy and reviewed studies for metformin, losartan, and cysteamine in patients with NAFLD or NASH (old terminology).4 None of these trials found improvements in their primary outcomes, and the AASLD did not make recommendations for their use. The guidelines also discussed the use of resmetirom, noting that the safety and efficacy have not been established in patients less than 18 years of age, and the GLP-1 receptor agonists, none of which are approved in pediatric patients specifically for MASLD or MASH; however, several agents in this class are approved for diabetes or obesity in pediatric patients. The AASLD pediatric pharmacotherapy recommendations are summarized in Table 2.

Table 2. AASLD pharmacotherapy recommendations for pediatric patients with MASLD/MASH.4
No pharmacotherapies are currently recommended or approved as specific treatments for MASLD or MASH in children.
Herbal supplements should not be used to treat MASLD, as none have been proven effective, and many carry the risk of hepatotoxicity.
For patients aged 18 and older, medications approved for the treatment of MASH with moderate to advanced fibrosis in adults, such as resmetirom, may be prescribed by pediatric gastroenterologists in accordance with their approved indications.
Medications approved for use in children aged 12 years and older to treat obesity or type 2 diabetes may be considered for children with MASLD who meet the approved criteria for these conditions.
  • GLP-1 receptor agonists are of particular interest, given that adult clinical trials have demonstrated benefits for MASH resolution in adults with MASLD. However, these findings cannot yet be applied to pediatric patients. The effectiveness of these medications in treating MASLD in children remains untested.
Medications associated with excess weight gain or promote hepatic steatosis should be avoided in children with MASLD unless clinically necessary and no alternatives are available.
Abbreviations: GLP-1=glucagon-like peptide-1; MASH=metabolic dysfunction-associated steatohepatitis; MASLD=metabolic dysfunction-associated steatotic liver disease.

Currently there is no evidence to support the use of resmetirom in pediatric patients with MASLD/MASH; however, the recent evidence for GLP-1 receptor agonists requires further review.

GLP-1 receptor agonists for MASLD/MASH in pediatric patients
No prospective clinical trials evaluating GLP-1 receptor agonists in MASLD/MASH were identified; however, retrospective, observational studies were recently published.7,8

Tou et al conducted a single-center retrospective study in patients 18 years of age and younger who had a MASLD diagnosis from the Children’s Hospital of Philadelphia.7 All patients were prescribed a GLP-1 receptor agonist between January 2018 and January 2024 and had evidence of steatosis on imaging or liver biopsy plus one cardiometabolic criteria and elevated alanine aminotransferase (ALT $\gt$22 U/L for females and $\gt$26 U/L for males). Cardiometabolic risk factors for pediatric patients included: body mass index (BMI ≥85th percentile, waist circumference $\gt$95th percentile, or ethnicity adjusted equivalent); elevated glucose (≥100 mg/dL fasting, ≥200 mg/dL random, or ≥140 mg/dL 2-hour post-load glucose), elevated hemoglobin A1c (HbA1c ≥5.7%), or type 2 diabetes; elevated blood pressure (≥130/80 mmHg or ≥95th percentile if $\lt$13 years old or ≥130/85 mmHg if ≥13 years old) or receiving hypertension treatment; elevated triglycerides (≥100 mg/dL if $\lt$10 years old or ≥150 mg/dL if ≥10 years old) or lipid lowering treatment; low HDL (≤40 mg/dL) or lipid lowering treatment.8

The primary outcome was change in serum ALT levels from baseline to 6 months and end of therapy. A total of 42 patients met inclusion criteria with 44% receiving liraglutide, 27% semaglutide, 25% dulaglutide, and 4% exenatide. Most patients were receiving GLP-1 receptor agonists for type 2 diabetes (71%) and the remainder (29%) for obesity. The mean age of patients was 15 years. At baseline, the mean ALT of the whole population was 118 U/L which was reduced to 81 U/L at end of therapy (mean change, -37 U/L; p=0.004). In those with 6-month data (N=14), baseline ALT was 130 U/L and was reduced to 74 U/L at 6 months (mean change, -56 U/L; p=0.042). Improvements in HbA1c (0.9%) and triglycerides (46 mg/dL) were found at 6 months, and improvements in gamma-glutamyl transferase (GGT 18 U/L), aspartate aminotransferase (AST 19 U/L), and HbA1c (0.6%) were also noted at end of therapy. There were no significant improvements in BMI, HDL, LDL, or blood pressure.

Similarly, Choi et al conducted a retrospective case series from the Children’s Healthcare of Atlanta Type 2 Diabetes Clinic. A total of 9 patients with a diagnosis of pre-diabetes or type 2 diabetes who were prescribed a subcutaneous GLP-1 receptor agonist and had an ALT level more than twice the upper limit of normal in the absence of other liver diseases or a clinician-provided diagnosis of MASLD were included. Age ranged from 14 to 20 years and agents included liraglutide (n=5), dulaglutide (n=3), exenatide (n=1), and the combination of lixisenatide/glargine (n=1). Patients were treated for an average of 321 days before final ALT measurement, 360 days for HbA1c measurement, and 349 days for BMI measurement. At the final follow-up, the median ALT was 34 U/L (interquartile range [IQR], 24 to 58), corresponding to a percentage decrease of 61.2% (IQR, 59.7% to 80.1%) from baseline. The median BMI was 37.6 kg/m2 (IQR, 36.0 to 40.2), representing a percent decrease of 2.4% (IQR, 0 to 12.3%) from baseline. The median HbA1c was 5.6% (IQR, 5.4 to 6.8), indicating a percent decrease of 25.8% (IQR, 21.5% to 37.4%) from baseline.

Conclusion
Resmetirom and semaglutide, the FDA-approved agents for adults with MASH, have not been prospectively evaluated in pediatric patients for MASH treatment. Currently there is no evidence for resmetirom in pediatric patients. However, semaglutide and other GLP-1 receptor agonists have been found to have beneficial effects for patients with MASLD in observational studies of patients who had concomitant obesity or type 2 diabetes. Although the evidence for GLP-1 receptor agonists for MASLD in pediatric patients is limited, GLP-1 receptor agonist safety and efficacy have been more thoroughly evaluated for pediatric patients for other indications (type 2 diabetes and obesity).

Lifestyle modifications including diet and exercise should be the mainstay of treatment for pediatric patients with MASH/MASLD. Pediatric patients should receive treatment for concomitant conditions including type 2 diabetes and obesity. The GLP-1 receptor agonists are a promising treatment for pediatric patients with MASH/MASLD and obesity or type 2 diabetes.

References

  1. Schwimmer JB, Biddinger SB, Ibrahim SH. MASLD in children: integrating epidemiological trends with mechanistic and translational advances. J Clin Invest. 2025;135(13):e186422. doi:10.1172/JCI186422
  2. Kohli R. Overview of Metabolic Dysfunction-Associated Steatohepatitis in Children. Gastroenterol Hepatol (N Y). 2025;21(4):255-258.
  3. New MASLD Nomenclature. American Association for the Study of Liver Diseases (AASLD). Accessed February 11, 2026. https://www.aasld.org/new-masld-nomenclature
  4. Xanthakos SA, Ibrahim SH, Adams K, et al. AASLD Practice Statement on the evaluation and management of metabolic dysfunction-associated steatotic liver disease in children. Hepatology. 2025;82(5):1352-1394. doi:10.1097/HEP.0000000000001368
  5. Rinella ME, Neuschwander-Tetri BA, Siddiqui MS, et al. AASLD practice guidance on the clinical assessment and management of nonalcoholic fatty liver disease. Hepatology. 2023;77(5):1797-1835. doi: 10.1097/HEP.0000000000000323
  6. Chopra S, Lai M. Management of metabolic dysfunction-associated steatotic liver disease (nonalcoholic fatty liver disease) in adults. In: Connor RF, ed. UpToDate. Wolters Kluwer. Updated January 21, 2026. Accessed February 12, 2026. https://www.uptodate.com/
  7. Tou AM, Panganiban J. Glucagon-like peptide-1 receptor agonists in pediatric metabolic dysfunction-associated steatotic liver disease. J Pediatr Gastroenterol Nutr. 2026;82(1):146-155. doi:10.1002/jpn3.70242
  8. Rinella ME, Lazarus JV, Ratziu V, et al. A multisociety Delphi consensus statement on new fatty liver disease nomenclature. Hepatology. 2023;78(6):1966-1986. doi:10.1097/HEP.0000000000000520
  9. Choi E, Ramirez Tovar A, He Z, Soler Rodriguez DM, Vos MB, Arora S, Fadoju D. Glucagon-like Peptide-1 Receptor Agonists—A Potential New Medication for Pediatric Metabolic-Dysfunction-Associated Steatotic Liver Disease (MASLD). Children. 2024; 11(3):275. https://doi.org/10.3390/children11030275

Prepared by:
Courtney Krueger, PharmD, BCPS
Clinical Assistant Professor, Drug Information Specialist
University of Illinois at Chicago Retzky College of Pharmacy

March 2026

The information presented is current as of February 12, 2026. This information is intended as an educational piece and should not be used as the sole source for clinical decision-making.