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Metabolic dysfunction-associated steatotic liver disease in pediatric patients: Definitions and phenotypes

Metabolic dysfunction-associated steatotic liver disease in pediatric patients: Definitions and phenotypes
Term/phenotype[1] Previous nomenclature[2] Definitions
Steatotic liver disease Fatty liver disease
  • Liver disease of any cause that results in hepatic steatosis (on imaging or biopsy).
Metabolic dysfunction-associated steatotic liver disease (MASLD) Nonalcoholic fatty liver disease (NAFLD)
  • Refers to steatotic liver disease associated with cardiometabolic dysfunction.
  • Abnormal liver steatosis is typically defined as fat >5% of the liver by imaging or histologic estimation.
  • Requires the presence of at least 1 of 5 cardiometabolic risk factors*.
  • The diagnosis of isolated MASLD requires the absence of significant alcohol (ie, <140 g/week for females and <210 g/week for males), monogenetic diseases, or medications that cause steatosis. MASLD may coexist with these other causes.
Metabolic dysfunction-associated steatohepatitis (MASH) Nonalcoholic steatohepatitis (NASH)
  • A definitive diagnosis of MASH can only be made by liver biopsy, but this is not always necessary for clinical management.
Definite MASH  
  • Hepatic steatosis with lobular inflammation, ballooning injury to hepatocytes, with or without fibrosis.
Borderline MASH, zone 3 pattern Type 1
  • Has some but not all components of MASH injury, in a venule (zone 3)-centered injury pattern or confluent pattern.
Borderline MASH, zone 1 pattern Type 2
  • Has some but not all components of MASH in a portal predominant (zone 1)-centered injury pattern, often without ballooning and more commonly seen in younger prepubertal children.
MASLD with fibrosis or cirrhosis NAFLD with fibrosis or cirrhosis
  • MASLD or MASH with periportal, portal, sinusoidal, or bridging fibrosis or cirrhosis.
MASLD and increased alcohol intake (MetALD) None (new category)
  • Moderate alcohol use is defined as 140 to 350 g/week for females and 210 to 420 g/week for males.
  • This range of alcohol intake defines a spectrum between MASLD-predominant and alcohol-predominant disease.
Other terms such as "presumed NAFLD" (also "clinical NAFLD" or "suspected NAFLD") are terms used in the literature with varying meanings. These terms are often used when a biopsy has not been performed to confirm the diagnosis.

A1C: glycated hemoglobin; BMI: body mass index; BP: blood pressure; HDL: high-density lipoprotein; MASH: metabolic dysfunction-associated steatohepatitis; MASLD: metabolic dysfunction-associated steatotic liver disease; MetALD: MASLD and increased alcohol intake; NAFLD: nonalcoholic fatty liver disease; NASH: nonalcoholic steatohepatitis.

* Pediatric criteria for cardiometabolic risk factors are[1]:
  • Overweight/obesity – BMI ≥85th percentile for age/sex (BMI Z-score ≥+1) or waist circumference >95th percentile (may vary by ethnicity or race).
  • Prediabetes/diabetes – A1C ≥5.7% (39 mmol/L), fasting serum glucose ≥100 mg/dL (5.6 mmol/L), random serum glucose ≥200 mg/dL (11.1 mmol/L), 2-hour oral glucose tolerance test ≥140 mg/dL (7.8 mmol/L), or established diagnosis of type 2 diabetes.
  • Hypertension – For age ≥13 years, BP ≥130/80 mmHg; for age <13 years, BP ≥95th percentile or ≥130/80 (whichever is lower); or on antihypertensive treatment.
  • Hypertriglyceridemia – For age ≥10 years, triglyceride ≥150 mg/dL (1.7 mmol/L); for age <10 years, triglyceride ≥100 mg/dL (1.15 mmol/L); or on lipid-lowering treatment.
  • Low HDL – HDL ≤40 mg/dL (1 mmol/L) or on lipid-lowering treatment.

¶ UpToDate suggests using BP ≥130/80 as a cardiometabolic risk factor for children ≥13 years; this is the threshold for defining hypertension in this age group, as defined by the American Heart Association[3]. Rinella[2] used BP ≥130/85, which is the threshold for defining metabolic syndrome in adolescents that was proposed by the International Diabetes Federation in 2007 but has not been reevaluated since then.

References:
  1. Rinella ME, Lazarus JV, Ratziu V, et al. A multi-society Delphi consensus statement on new fatty liver disease nomenclature. Hepatology 2023.
  2. Vos MB, Abrams SH, Barlow SE, et al. NASPGHAN clinical practice guideline for the diagnosis and treatment of nonalcoholic fatty liver disease in children: Recommendations from the Expert Committee on NAFLD (ECON) and the North American Society of Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN). J Pediatr Gastroenterol Nutr 2017; 64:319.
  3. Flynn JT, Kaelber DC, Baker-Smith CM, et al. Clinical practice guideline for screening and management of high blood pressure in children and adolescents. Pediatrics 2017; 140:e20171904.
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