NAFLD: nonalcoholic fatty liver disease; ALT: alanine aminotransferase; ULN: upper limit of normal; CBC: complete blood count; AST: aspartate aminotransferase; GGTP: gamma-glutamyl transferase; HAV: hepatitis A virus; HBV: hepatitis B virus; HCV: hepatitis C virus; MRI-PDFF: magnetic resonance imaging proton density fat fraction.
* Also screen children who are overweight (body mass index 85th to 95th percentile) if other risk factors are present, such as acanthosis nigricans (or other signs of insulin resistance) or a family history of NAFLD.
¶ This algorithm applies to asymptomatic children. Viral infections can transiently increase serum aminotransferase levels. 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 or elevated direct bilirubin elevated international normalized ratio.
◊ ULN for ALT is defined as >22 unit/L for girls and >26 unit/L for boys.
§ 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 (PI) phenotype. PI phenotypes associated with liver disease are ZZ or SZ.
¥ Screening for genetic liver diseases is performed for selected patients, depending on risk factors, level of concern, and results of other tests.
‡ Indications for liver biopsy in patients with suspected NAFLD have not been established, and practice varies. Liver biopsy is considered the gold standard for diagnosis of NAFLD. In our practice, we suggest liver biopsy for patients who have had ALT elevations >2 x ULN for 6 or more months, or for those with ALT >80 or red flags for advanced liver disease, as outlined above. The decision about whether to perform a biopsy is made collaboratively with the patient and their family.
† Although ultrasound is not recommended for screening or quantification of hepatic steatosis, it may be useful. We suggest a liver ultrasound as part of the full evaluation, particularly if the history and physical examination suggest the presence of gallbladder disease or complications such as portal hypertension (eg, splenomegaly). Magnetic resonance imaging may be used instead of ultrasound, where available, to rule out a biliary abnormality and can also provide a semi-quantitative measure of liver fat.
