Where to refer a child with fatty liver disease?

Referral Guidelines for Children with Fatty Liver Disease

Children with fatty liver disease should be referred to a pediatric gastroenterologist or hepatologist when ALT remains elevated for more than 3 months, especially if ALT is >2x upper limit of normal or if there are signs of advanced liver disease. 1

Initial Assessment and Screening

• Screening for NAFLD should begin at age 10 years in children with obesity or those with BMI in the 85th-94th percentile with other risk factors 1
• ALT is the preferred initial screening test, with values >2x upper limit of normal (>44 U/L for girls, >52 U/L for boys) warranting referral to pediatric gastroenterology 1
• Children with fatty liver who are very young (<10 years) or not overweight should be tested for monogenic causes of chronic liver disease including fatty acid oxidation defects, lysosomal storage diseases, and peroxisomal disorders 1, 2
• Low serum titers of autoantibodies are often present in children with NAFLD, but higher titers with elevated aminotransferases and high globulins should prompt evaluation for possible autoimmune hepatitis 1, 2

When to Refer to a Specialist

Immediate Referral Criteria:

• ALT >80 IU/L (indicates high risk for advanced liver disease) 1
• Presence of signs or symptoms of liver disease (jaundice, hepatomegaly, splenomegaly) 1
• Children with red flags including mental status changes, unusual bleeding/bruising, persistent vomiting/diarrhea 2

Delayed Referral After Initial Management:

• ALT remains elevated >ULN (>26-51 U/L for boys, >22-43 U/L for girls) after 3-6 months of lifestyle intervention 1, 3
• Presence of risk factors for progressive disease (rapid increase in BMI, development of insulin resistance/type 2 diabetes) 1
• Family history of severe NAFLD or cirrhosis 1

Specialist Evaluation

• Pediatric gastroenterologists/hepatologists will consider liver biopsy in cases with uncertain diagnosis, to rule out drug hepatotoxicity, or when there are multiple potential diagnoses 1
• Non-invasive assessment may include transient elastography (FibroScan), MR elastography, or acoustic radiation force impulse imaging to evaluate fibrosis 1
• Comprehensive evaluation for comorbidities including type 2 diabetes, dyslipidemia, and hypertension should be performed 4

Management Approach

• Intensive lifestyle modification is the first-line treatment for children with NAFLD 1
• Weight reduction of >20% has been shown to improve serum ALT and liver steatosis in most children with NAFLD 1
• Multidisciplinary care involving hepatologists, endocrinologists, dietitians, and exercise physiologists may lead to better outcomes 5
• Vitamin E (800 IU/day) may be considered for children with biopsy-proven NASH, as it has shown improvement in liver histology 1
• Metformin has not shown benefit in children with NAFLD and is not recommended 1

Caution and Pitfalls

• NAFLD is underdiagnosed in children due to lack of recognition or screening by healthcare providers 1
• Normal ALT does not exclude NAFLD, especially in morbidly obese children who should undergo ultrasound even with normal liver enzymes 6
• Progression to cirrhosis can occur in children with NAFLD, with studies showing that 11% of referred children with NAFLD already have advanced fibrosis 1, 7
• Repeated screening is warranted due to the progressive nature of NAFLD, with screening every 3 years being practical as it parallels the screening frequency for type 2 diabetes 1

By following these referral guidelines, clinicians can ensure timely and appropriate specialist care for children with fatty liver disease, potentially preventing progression to more severe liver disease and improving long-term outcomes.