Tag Archives: steatotic liver disease

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):

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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Increased Mortality in Pediatric Steatotic Liver Disease Plus One

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From UCSD 4/28/25: Children with Liver Disease Face Dramatically Higher Risk of Early Death (via Jeff Schwimmer’s X feed)

The findings, published April 22, 2025 in Hepatology, the scientific journal of the American Association for the Study of Liver Diseases, come from the Longitudinal InVestigation Evaluating Results of Steatosis (LIVERS) study, which followed 1,096 children over an average of 8.5 years. Nearly half of all deaths in the cohort were liver-related, and the overall mortality rate was 40 times higher than that of similar peers in the general U.S. population...

The retrospective cohort study used medical records and National Death Index data to follow children ages 2 to 18 who were diagnosed with MASLD between 2000 and 2017. Over an average of 8.5 years of follow-up, 3.4% of children had died…

In addition to the risk of early death, many children in the study developed serious health problems while still in their teens or twenties. These included high blood pressure (14%), obstructive sleep apnea (9.5%) and type 2 diabetes (7.3%). Problems with blood fats, such as high triglycerides or low HDL, were even more common — making dyslipidemia, the presence of abnormal levels of fats (lipids) in the blood, the most frequent complication overall.

Link to study: JB Scwimmer et al Hepatology ():10.1097/HEP.0000000000001357. Long-term mortality and extrahepatic outcomes in 1,096 children with MASLD: A retrospective cohort study

My take: Since this was a retrospective single center study, the severity of the findings may be different with a more-representative national cohort. Nevertheless, this study shows that MASLD has serious consequences including premature death and numerous comorbidities.

Related article: J Panganiban et al. Obesity Pillars 2025: 14. https://doi.org/10.1016/j.obpill.2025.100164. Open Access! Metabolic dysfunction-associated steatotic liver disease (MASLD) in children with obesity: An Obesity Medicine Association (OMA) and expert joint perspective 2025. This Obesity Medicine Association (OMA) Expert Joint Perspective is a comprehensive review (~28 pages) of steatotic liver disease (SLD), metabolic dysfunction-associated steatotic liver disease (MASLD), and metabolic dysfunction-associated steatohepatitis (MASH) in children with obesity.

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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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MASH Treatment: Curcumin Shows Promising Results

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G Musso et al. Hepatology 2025; 81: 560-575. Effect of phospholipid curcumin Meriva on liver histology and kidney disease in nonalcoholic steatohepatitis: A randomized, double-blind, placebo-controlled trial

“Let food be thy medicine” is a well-known phrase usually attributed to Hippocrates (though it is unclear if he said this). Regardless, this study indicates that added curcumin in the diet could be beneficial for steatotic liver disease.

Methods: In this double-blind trial, 52 patients with biopsy-proven NASH (71% with stage ≥F2 fibrosis, 58% with stage A2-G2/A2-G3a chronic kidney disease) were randomized 1:1 to receive Meriva 2 g/d (1 g BID) or placebo for 72 weeks. Meriva is a formulation of curcumin extract with phospholipids that has improved oral bioavailability of curcumin metabolites.

Key findings:

  • Sixteen (62%) patients on Meriva (curcumin) versus 3 (12%) patients on placebo had NASH resolution (RR = 5.33)
  • hirteen (50%) patients on Meriva versus 2 (8%) patients on placebo had ≥1 stage fibrosis improvement (RR = 6.50)
  • Eleven (42%) patients on Meriva versus 0 (0%) on placebo had regression of significant liver fibrosis (RR = 18.01)
  • Thirteen (50%) patients on Meriva versus 0 (0%) on placebo had chronic kidney disease regression (RR = 10.71)
  • Compared with placebo, Meriva improved eGFR (difference in adjusted eGFR change: +3.59 [2.96–4.11] mL/min/1.73 m2/y, p = 0.009), fasting glucose(−17 mg/dL; 95% CI = −22, −12), HbA1c (−0.62%; 95% CI = −0.87%, −0.37%), LDL-C (−39 mg/dL; 95% CI = −45, −33), triglycerides (−36 mg/dL, 95% CI = −46, −26), HDL-C (+10 mg/dL; 95% CI = +8, +11), and inflammatory markers
  • The observed benefits were associated with downregulation of hepatic NF-kB which is a proinflammatory transcription factor and a known curcumin target

My take: A larger multicenter study is needed to confirm these promising results. This study shows that dietary changes and lifestyle modification remain important tools in treating MASH (aka NASH).

Related editorial (open access!): S Zelber-Sagi, JM Schattenberg. Hepatology 2025; 81: 399-401. Is curcumin the new kid on the block for the treatment of MASH?

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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.

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.

Key Advances in 2024: An Overview from GutsandGrowth (Part 2)

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This year I had the opportunity to give a lecture to our group that reviewed much of the important advances that happened in 2024. Here are some of the slides (if you have any trouble reading the slides, you can search for the original blog post using author name).

More Data Indicating GLP-1 Efficacy for MASH

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GI and Hepatology News, Open Access: Watershed Moment’: Semaglutide Shown to Be Effective in MASH (November 2024): “At 72 weeks, a 2.4-mg once-weekly subcutaneous dose of semaglutide demonstrated superiority, compared with placebo, for the two primary endpoints: Resolution of steatohepatitis with no worsening of fibrosis and improvement in liver fibrosis with no worsening of steatohepatitis.”

“ESSENCE (NCT04822181) is an ongoing multicenter, phase 3 randomized, double-blind, placebo-controlled outcome trial studying semaglutide for the potential treatment of MASH.” Cohort: N=1200, biopsy-defined MASH and fibrosis, stages F2 and F3…”After initiation, the semaglutide dosage was increased every 4 weeks up to 16 weeks when the full dose (2.4 mg) was reached.”

Key findings:

  • 62.9% of those in the semaglutide group and 34.1% of those in the placebo group reached resolution of steatohepatitis with no worsening of fibrosis. 
  • 37% of those in the semaglutide group and 22.5% of those in the placebo group had improvement in liver fibrosis with no worsening of steatohepatitis
  • Weight loss was also significant, with a 10.5% reduction in the semaglutide group compared with a 2% reduction in the placebo group
  • No new safety signals were identified
  • Cardiometabolic risk factors improved as well, with changes in blood pressure measurements, hemoglobin A1c scores, and cholesterol values.
  • 20%-40% improvements in liver enzymes and noninvasive fibrosis markers, such as ELF and vibration-controlled transient elastography liver stiffness.

My take: This expected finding indicates that more GLP-1 agents are likely to be approved for MASH treatment. Survodutide received “U.S. FDA Breakthrough Therapy” in October 2024.

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Manuel Antonio National Park, Costa Rica

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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