Tag Archives: MASLD

AASLD Practice Statement on the evaluation and management of metabolic dysfunction–associated steatotic liver disease in children

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S Xanthakos et al. Hepatology 2025; 82: 1352-1394. AASLD Practice Statement on the evaluation and management of metabolic dysfunction–associated steatotic liver disease in children (Behind paywall)

The review of pediatric MASLD addresses epidemiology, pathophysiology, natural history, screening, diagnosis, treatment, comorbidity management, outcome monitoring, and transition of care. It also discusses the implications of the 2023 nomenclature revision, which emphasizes evaluating both hepatic steatosis and cardiometabolic risk factors.

Some key points:

  • Box 1 outlines numerous (32) research priorities, including the need for prospective longitudinal cohort studies.
  • “Globally, the estimated prevalence of MASLD in children is 7.6%, making it the most common cause of chronic liver disease in children”
  • Figure 4 describes the interplay between risk factors for MASLD included genetic predisposition, prenatal factors and environmental exposures
  • Figure 5 summarizes comorbid conditions which include obstructive sleep apnea, prediabetes/diabetes, cardiovascular disease (dyslipidemia, hypertension, left ventricular hypertrophy), anxiety/depression, reduced bone mineral density, renal dysfunction and polycystic ovarian syndrome. Table 6 summarizes evaluation and initial management with most of these conditions. Yearly screening for diabetes in children with MASLD is recommended.
  • ALT remains most common screening test with >26 U/L for adolescent males and >22 U/L for adolescent females having optimal sensitivity (>80-85%). We recommend “screen for MASLD in children aged 10 years or older with overweight and cardiometabolic risk factors or family history or obesity.” Annual screening recommended if at risk.
  • Table 2 provides a long list of medications which may promote weight gain. These include antihistamines, steroids, some contraceptives, anticonvulsants, antidepressants, antipsychotics, methotrexate, and doxycycline

Diagnostic evaluation:

  • Diagnosis of MASLD requires confirmation of steatosis (by imaging or biopsy) in addition to the presence of at least one cardiometabolic risk factor. ALT elevation with a cardiometabolic risk factor is insufficient.
  • “Consider liver biopsy in cases where there is uncertainty, especially if ALT levels are persistently elevated (>2 times the ULN)”
  • Table 3 lists inborn errors of metabolism and monogenetic diseases which may cause childhood-onset steatotic liver disease. Evaluation of inborn errors of metabolism should be considered if atypical signs or symptoms, such as early onset (<3 yrs), rapidly progressive, absence of obesity, or other organ involvement (especially neurological)
  • Table 4 summarizes imaging modalities to assess steatosis and fibrosis in children. Only MRI-PDFF has been validated in children (for steatosis)
  • Table 5 describes BMI classification in children (WHO and AAP)
  • Lifestyle treatments are detailed including diet (reduction of added sugars, Mediterranean diets) and exercise
  • Emerging medications are reviewed. However, practice statement notes “No pharmacotherapies are currently recommended or approved as specific treatments for MASLD or MASH in children…Medications approved for use in children ages 12 years and older to treat obesity or type 2 diabetes may be considered for children with MASLD.”

My take: This is a comprehensive practice guidance. It emphasizes an extensive diagnostic evaluation. The threshold for liver biopsy is relatively low in this guidance. As more data emerges, it is likely that more emphasis will be placed on the use of pharmacotherapies.

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Disclaimer: This blog, gutsandgrowth, assumes no responsibility for any use or operation of any method, product, instruction, concept or idea contained in the material herein or for any injury or damage to persons or property (whether products liability, negligence or otherwise) resulting from such use or operation. These blog posts are for educational purposes only. Specific dosing of medications (along with potential adverse effects) should be confirmed by prescribing physician.  Because of rapid advances in the medical sciences, the gutsandgrowth blog cautions that independent verification should be made of diagnosis and drug dosages. The reader is solely responsible for the conduct of any suggested test or procedure.  This content is not a substitute for medical advice, diagnosis or treatment provided by a qualified healthcare provider. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a condition.

Diets for Obesity and Steatotic Liver Disease Plus Patient Information from FISPGHAN

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S Karjoo et al. JPGN 2025;81:485–496. Evidence-based review of the nutritional treatment of obesity and metabolic dysfunction-associated steatotic liver disease in children and adolescents

This invited commentary reviews the data for several diets that may improve weight loss and metabolic dysfunction-associated steatotic liver disease (MSALD).

Several points:

  • “Extremely restricted plant‐based diets may have deficiencies of vitamin D, calcium, and vitamin B12 which are nutrients found in animal products, and can be minimized by vitamin supplementation or increasing consumption of fish, mushrooms, egg yolk, cod liver oil, salmon, herring, and sole fish. VitaminB12 supplementation is recommended in plant‐based diets because this vitamin is primarily found in animal products”
  • Table 1 compares the structure of these diets and their advantages/drawbacks
  • “Low to moderate weight loss can be seen in the anti-inflammatory diet, plant-based diets, or Mediterranean diet. These diets are nutritionally complete. However, restrictive plant-based diet carries a risk of micronutrient deficiencies, which can be corrected with appropriate supplementation. These diets are effective in treating MASLD independent of weight loss due to their anti-inflammatory profile.”
  • “The ketogenic diet, certain carbohydrate-restricted diets, and intermittent fasting can lead to more weight loss but carry a higher risk of malnutrition. Children on these diets must be followed by nutritionists.”

My take: Each of the diets reviewed can help MASLD and obesity. Most patients pursuing dietary therapy would benefit from working with a nutritionist.

Related news: TEVA Press release, August 28, 2025: Generic liraglutide (need for daily injections) is now available.

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Also, related patient advice from Federation of International Societies for Pediatric Gastroenterology, Hepatology, and Nutrition (FISPGAN) –outlines risk factors and prevention tips for metabolic dysfunction-associated steatotic liver disease (MASLD):

Clever Study: Hepatic Steatosis is Common in Overweight/Obese Children in First Four Years of Life

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AO Glenn et al. JPGN 2025;81:679–682. Sonographic evidence of hepatic steatosis is highly prevalent in at-risk children under 4 years of age

This study had a clever design: the authors examined the liver findings from overweight/obese children (n=168) who underwent renal ultrasounds to help determine the frequency of hepatic steatosis. Quantification of the hepatorenal index (HRI) by ultrasound has been shown to provide moderate diagnostic performance for detecting hepatic steatosis in children. (Ref: Frankland MP et al. Diagnostic performance of ultrasound hepatorenal index for the diagnosis of hepatic steatosis in children. Pediatr Radiol. 2022; 52(7): 1306-1313)

This design helped avoid a selection bias present in most studies which have examined ultrasonography in children with elevated liver enzymes. The authors did try to correlate the imaging findings with blood tests. Serum laboratory data were available for 50 patients at a mean interval of 115 days (0–366) from the ultrasound examination.

Key findings:

  • 91 (54%) patients had an abnormally elevated HRI (>1.75). An abnormally elevated HRI was present in 58% (50/86) of patients with overweight and 50% (41/82) of patients with obesity
  • Of the 12 patients with abnormal ALT, 5 (42%) had an abnormal ultrasound HRI and 7 (58%) had a normal ultrasound HRI

Discussion points:

“MASLD can occur at a very young age and should be considered in at-risk patients. Importantly, only 21% (5/24) of the patients with imaging evidence of steatosis and available labs had elevated ALT and 58% (7/12) of patients with an elevated ALT did not have imaging evidence of steatosis, suggesting that ALT may not be a useful biomarker for MASLD screening at this age.”

My take: Hepatic steatosis is likely present in about half of children with early onset overweight/obesity. ALT values are often normal in this cohort.

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The Rocky Mountains, Landers Peak by Albert Bierstadt at the Metropolitan Museum of rt

EAT-Lancet Diet Associated with Reduced Risk of MASLD

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From the commentary: “In 2019, the EAT-Lancet Commission on Food, Plant, and Health proposed a planetary health diet, known as the EAT-Lancet reference diet, that promotes human health and sustainable food production globally…and recommends fruits, vegetables, whole grains, plant-based proteins (eg. legumes, nuts) and unsaturated plant oils, with limited or moderate amounts of animal-based proteins such as meat and dairy….[it] has been associated with multiple health benefits, including reducing the risks of type 2 diabetes, cardiovascular disease, certain cancers, and all-cause mortality.”

Methods: This prospective multicohort study comprised more than 191,000 adults from several cohorts. In addition, 228 Chinese adults from the Prospective Epidemic Research Specifically of Non-alcoholic Steatohepatitis (PERSONS) with biopsy-proven MASLD were included.

Key findings:

  • Participants in the highest tertiles of the EAT-Lancet diet index had a lower risk of MASLD compared with those in the lowest tertiles with HR ranging in different cohorts from 0.73 to 0.87
  • Liver-controlled attenuation parameter decreased with increasing the diet index in individuals with biopsy-proven MASLD (β = −5.895

My take (borrowed from the authors): Adherence to the EAT-Lancet reference diet was inversely associated with the risk of MASLD as well as its severity.

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Key Insights on MASLD from Dr. Marialena Mouzaki

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Dr. Marialena Mouzaki recently gave an excellent ground rounds at Children’s Healthcare of Atlanta. My notes below may contain errors in transcription and in omission. Along with my notes, I have included many of her slides (with permission).

Key points:

  • Epidemiology: Metabolic associated steatotic liver disease (MASLD) is very common and increasing in prevalence
  • There is new terminology and new diagnostic thresholds
  • Treatment cornerstone relies on lifestyle changes including diet modifications and exercise. Small weight reductions (10 lbs in adults)/improvement in BMI (z reduction of >0.25) can be beneficial
  • Diet: No specific diet has proven more effective than others (eg. low carb, Mediterranean). Avoiding simple sugars is helpful
  • Exercise: US children do not get enough physical activity (goal 1 hour daily). Exercise has not been studied well for pediatric MASLD but it has been proven to reduce cardiovascular disease and premature death
  • Medications: Medications are not part of routine care for pediatric MASLD in 2025 When they are available, use without lifestyle changes could be detrimental (eg. sarcopenia, worse cardiometabolic profile, nutritional deficiencies)
  • Multiple GLP-1 RA-containing agents appear promising (Semaglutide, tirzepatide, survodutide). Resmetirom is FDA approved for the treatment of MASLD with stage 2-3 fibrosis in adults.
  • Treat comorbidities like diabetes, obstructive sleep apnea (OSA), dyslipidemia and hypertension. Treatment of OSA may help MASLD
  • The leading cause of mortality in adults with MASLD is due to cardiovascular disease

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Pharmacological Management of Pediatric Steatotic Liver Disease

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RARA Jaoudeh et al. J Pediatr Gastroenterol Nutr. 2025;80:14–24; Pharmacological management of pediatric metabolic dysfunction-associated steatotic liver disease

Key points:

  • Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have demonstrated efficacy against adult MASLD. “In patients ≥12 years of age with obesity (BMI ≥ 95th percentile), we recommend the use of GLP-1RA—along with dietary and lifestyle modifications—in those who have MASLD or MASH, and 1 additional metabolic comorbidity (hypertension, prediabetes, polycystic ovary syndrome, dyslipidemia, and obstructive sleep apnea) (Figures 1 and 2). Treatment with these agents should only be initiated after other causes of hepatic steatosis are ruled out.”
  • “GLP-1RA are effective in treating pediatric obesity and have shown to decrease liver enzyme levels which is likely indicative of their effect on MASLD.”
  • “It is important to note that phentermine/topiramate combination drug is approved for patients 12 years and older with obesity15 and can be used as a bridge for GLP-1RA therapy in cases where access to GLP-1RA is limited.”
  • GLP-1RA Dosing regimens are provided in Table 1. For example, “Semaglutide for weight loss is initiated at 0.25 mg once weekly subcutaneously and increased every 4 weeks in a stepwise fashion up to a maximum of 2.4 mg once weekly dose. The most common side effects are nausea and/or vomiting and can be worse the first few days a after dose increase. It is acceptable to delay dose escalation or reduce the target dose based on patient tolerance. Medication therapy should be evaluated for effectiveness after 12 weeks on a maximally tolerated dose.” And, “Liraglutide for weight loss is initiated at 0.6 mg daily subcutaneously and increased weekly in 0.6 mg increments up to a maximum 3 mg daily dose.”
  • Adverse effects: “Both liraglutide and semaglutide have been associated with thyroid C-cell tumors in animal studies37 and are contraindicated in patients with a personal or familial history of multiple endocrine neoplasia 2A and 2B and medullary thyroid carcinoma. Patients should be educated on symptoms of thyroid tumors—lump in the neck, difficulty breathing or swallowing, or persistent hoarseness—and treatment should be discontinued if these occur.37 GLP-1RA also increase the risk of pancreatitis and gallbladder disease especially with rapid weight loss.37 Liraglutide is contraindicated in pregnancy due to potential embryo-fetal defects shown in animal studies, and semaglutide should be discontinued if pregnancy occurs.10, 37“

Useful algorithm:

My take: GLP-RAs are likely to be used increasingly in adolescents with MASLD despite issues with insurance/affordability and need for chronic treatment. This is a helpful review.

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Disclaimer: This blog, gutsandgrowth, assumes no responsibility for any use or operation of any method, product, instruction, concept or idea contained in the material herein or for any injury or damage to persons or property (whether products liability, negligence or otherwise) resulting from such use or operation. These blog posts are for educational purposes only. Specific dosing of medications (along with potential adverse effects) should be confirmed by prescribing physician.  Because of rapid advances in the medical sciences, the gutsandgrowth blog cautions that independent verification should be made of diagnosis and drug dosages. The reader is solely responsible for the conduct of any suggested test or procedure.  This content is not a substitute for medical advice, diagnosis or treatment provided by a qualified healthcare provider. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a condition.

Limitations of MRE and TE in Assessing Liver Fibrosis in Pediatric MASLD

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N Ravanbakhsh et al J Pediatr Gastroenterol Nutr. 2024;79:1192–1198. Comparing imaging modalities in the assessment of fibrosis in metabolic dysfunction-associated steatotic liver disease

In this retrospective review with 77 patients who had liver biopsy-proven MASLD (2017-2023), the authors examined how well magnetic resonance elastoraphy (MRE) and transient elastography (TE) identified fibrosis.

Key findings:

  • Fibrosis was identified in 90% of liver biopsies
  • The area under the receiver operating characteristic curves (AUROC) of MRE and TE for detection of high-grade fibrosis were 0.817 and 0.750, respectively
  • Only 20% of patients had severe fibrosis on liver biopsy; thus, this is a limitation given the small number
Sensitivity in detecting advanced fibrosis, defined on liver biopsy was defined as Metavir Stage ≥ 3.

Conclusion of authors: “MRE and TE did not accurately predict high-grade fibrosis on liver biopsy. Between the two noninvasive imaging modalities, the correlation of identifying high-grade fibrosis was not statistically different.”

My take: Even MRE is not very accurate at identifying fibrosis. Given the huge numbers of individuals (pediatric and adult) with MASLD, the lack of reliable non-invasive markers is a problematic. As effective treatments become available, being able to determine if they are working is essential.

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AASLD Practice Changes for Metabolic Liver Disease in 2024

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V Chen et al. Hepatology 2024; doi: 10.1097/HEP.0000000000001112. Open Access!. Resmetirom therapy for metabolic dysfunction-associated steatotic liver disease: October 2024 updates to AASLD Practice Guidance

Key points:

  • Guidance recommends use of resmetirom (in adults) with F2-F3 fibrosis as determined by “imaging-based NILDAs, such as liver stiffness measurement (LSM) by vibration-controlled transient elastography (VCTE) or magnetic resonance elastography (MRE)…liver biopsy is not typically recommended for fibrosis staging in current clinical practice, [though] histologic examination remains the gold standard to quantify fibrosis.”
  • “Glucagon-like peptide 1 (GLP-1) and GLP-1/glucose-dependent insulinotropic polypeptide (GIP) receptor agonists are FDA approved for the treatment of type 2 diabetes and overweight/obesity. They reduce the risk of cardiorenal complications in addition to their effects on glycemic control and weight loss.17–25 While these pharmaceutical agents are not currently approved for the treatment of MASH, phase 2 randomized, placebo-controlled clinical trials of liraglutide, semaglutide, and tirzepatide have demonstrated their efficacy in reducing steatohepatitis without worsening fibrosis and, in the case of tirzepatide, decreasing fibrosis without worsening of steatohepatitis as well.”
  • “The most common treatment-emergent adverse events were diarrhea and nausea, which developed in 24% to 34% and 12% to 22% of resmetirom-treated participants, respectively…Development of hypothyroidism requiring levothyroxine replacement occurred in 1.8% of participants receiving resmetirom.”
  • The authors recommend assessing response with bloodwork and noninvasive imaging at 1 yr to help determine if therapy should be continued.

My take: This article provides practical advice for using resmetirom for MASLD.

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Non-Invasive Studies Often Fail to Detect Advanced Liver Fibrosis in Steatotic Liver Disease

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N Ravanbakhsh et al. JGPN 2024; https://doi.org/10.1002/jpn3.12368. Comparing imaging modalities in the assessment of fibrosis in metabolic dysfunction-associated steatotic liver disease

Key findings:

  • TE and MRE did not have high correlation with liver biopsy in the detection of high-grade fibrosis
  • Fibrosis was identified in 90% of liver biopsies with bridging fibrosis in 15 (19%) and cirrhosis in 1 (1%)
  • AUROC curves of MRE and TE for detection of high-grade fibrosis were 0.817 and 0.750, respectively, and not significantly different.

The authors note that previous adults studies suggest that MRE is more accurate in the identification of liver fibrosis than TE (MRE detected ≥ F1 fibrosis with an AUROC of 0.82, while TE detected fibrosis with an AUROC of 0.67).20 

My take: Trying to identify accurate non-invasive testing is crucial to help identify patients most in need of treatment and for limiting costs.

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Lean Patients with Inflammatory Bowel Disease Have Higher Risk of Steatotic Liver Disease Than Lean Patients Without IBD

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SJ Martinez-Dominguez et al. Inflammatory Bowel Diseases, Volume 30, Issue 8, August 2024, Pages 1274–1283, https://doi.org/10.1093/ibd/izad175 Open Acess! Inflammatory Bowel Disease Is an Independent Risk Factor for Metabolic Dysfunction–Associated Steatotic Liver Disease in Lean Individuals 

Methods: This was a cross-sectional, case-control study including 300 lean cases with IBD and 80 lean controls without IBD, matched by sex and age (median age ~45 yrs). All participants underwent a liver ultrasound, transient elastography, and laboratory tests. All patients with current or previous use of systemic steroid in the last 2 years were excluded from the analysis

Key Findings:

  • The lean IBD group showed a significantly higher prevalence of MASLD compared with lean non-IBD group (21.3% vs 10%; P = .022), but no differences were observed in the prevalence of significant liver fibrosis (4.7% vs 0.0%; P = 1.000)
  • No differences were found between the prevalence of MASLD in IBD and non-IBD participants who were overweight/obese (66.8% vs 70.8%; P = .442)
  • IBD was an independent risk factor for MASLD in lean participants (odds ratio [OR], 2.71) after adjusting for classic metabolic risk factors and prior history of systemic steroid use
Prevalence of metabolic dysfunction–associated steatotic liver disease (MASLD) in cases and controls according to body mass index (BMI) status. Blue bars: cases (inflammatory bowel disease). Red bars: controls (non–inflammatory bowel disease). P values in bold indicate statistical significance (P < .05).

My take: This study suggests that “chronic inflammation could play a role in MASLD development.” Also, this indicates that MASLD could be a reason for elevated LFTs in patients with IBD, even in lean patients.

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