Screening and evaluation for metabolic dysfunction-associated steatotic liver disease in children

ALT: alanine aminotransferase; AMA: antimitochondrial antibodies; anti-LKM: anti-liver-kidney microsomal antibodies type 1; ASMA: anti-smooth muscle antibodies; AST: aspartate aminotransferase; GGT: gamma-glutamyl transpeptidase; HbA1c: glycated hemoglobin; Ig: immunoglobulin; MASLD: metabolic dysfunction-associated steatotic liver disease; NAFLD: nonalcoholic fatty liver disease; MASH: metabolic dysfunction-associated steatohepatitis; T4: thyroxine; TSH: thyroid-stimulating hormone; tTg: tissue transglutaminase antibodies; ULN: upper limit of normal.

* Also screen children who are overweight (body mass index 85^th to 95^th percentile) if other risk factors are present, such as acanthosis nigricans (or other signs of insulin resistance) or a family history of MASLD or NAFLD. Younger children with overweight/obesity could also be screened if they have risk factors. NOTE: North American guidelines do not recommend obtaining imaging studies to screen all at-risk overweight and obese children for MASLD/NAFLD^[1]; however, European guidelines recommend obtaining both ALT and ultrasound in at-risk children^[2].

¶ This algorithm applies to asymptomatic children. If ALT is elevated in the context of a recent viral infection, repeat the test in 2 to 4 weeks and proceed with further evaluation if it remains elevated.

Δ Red flags for advanced liver disease, such as chronic fatigue, gastrointestinal bleeding, jaundice, splenomegaly, firm liver edge, enlarged left lobe, low platelets, low white blood cells, elevated direct bilirubin, or elevated international normalized ratio.

◊ For children 12 to 17 years, we define the ULN for ALT as 22 unit/L for girls and 26 unit/L for boys; for children 1 to <12 years, the ULN is 30 unit/L as they are supported by large population studies^[3-5].

§ The primary purpose of ultrasound is to evaluate for structural/anatomic causes of elevated liver enzymes (eg, gallbladder disease) or complications such as portal hypertension. It has poor sensitivity for detecting or quantifying hepatic steatosis. Vibration-controlled elastography (ie, FibroScan) provides information about steatosis and liver stiffness, but its utility for the diagnosis or monitoring of MASLD in children has not been established.

¥ Screening for Wilson disease consists of ceruloplasmin and/or 24-hour urine copper. Screening for alpha-1 antitrypsin deficiency is determination of the protease inhibitor phenotype. Protease inhibitor phenotypes associated with liver disease are ZZ or SZ.

‡ Screening for genetic liver diseases is performed for selected patients, depending on risk factors or signs/symptoms.

† Liver biopsy is considered the gold standard for diagnosis of MASH but may vary by practice setting. In our practice, we suggest liver biopsy for patients who have had ALT elevations >2 × ULN for 6 or more months or for those with ALT >80 unit/L, red flags for advanced liver disease^Δ, or features that suggest an alternate cause of the liver disease that requires biopsy for diagnosis.