What is the appropriate management for a child with elevated liver enzymes?

Management of Elevated Liver Enzymes in Children

Children with elevated liver enzymes require a low threshold for referral to a pediatric specialist, as the differential diagnosis is broader and more complex than in adults, with common adult causes being less prevalent in the pediatric population. 1

Immediate Red Flags Requiring Urgent Referral

The following findings mandate immediate specialist consultation or emergency evaluation:

• Coagulopathy, hypoglycemia, or encephalopathy – these indicate potential acute liver failure 2
• Ascites or signs of portal hypertension 2
• Unexplained clinical jaundice 1
• Conjugated hyperbilirubinemia in infants – may indicate biliary atresia requiring urgent intervention 2
• Suspicion of hepatic or biliary malignancy 1

Initial Clinical Assessment

History Components to Obtain

Document the following specific elements 1, 2:

• Family history of liver disease, hepatocellular carcinoma, or metabolic disorders 2
• Age and ethnicity (risk stratification for hepatitis B/C) 1
• Maternal, neonatal, nutritional, and developmental history in children 1
• Medication exposure including prescribed, over-the-counter, herbal supplements 1
• Symptoms: jaundice, abdominal pain, weight loss, pruritus 1
• Metabolic syndrome features: obesity, hypertension, diabetes 1
• Autoimmune disease history (personal or family) and inflammatory bowel disease 1

Physical Examination Findings

• Body mass index calculation 1
• Hepatosplenomegaly, ascites, and signs of chronic liver disease 1

Initial Laboratory Workup

Order a comprehensive metabolic panel and core liver aetiology screen 1, 2:

• ALT, AST, alkaline phosphatase, GGT 2
• Total and direct bilirubin 2
• Albumin and glucose 2
• Prothrombin time/INR to assess synthetic function 2
• Hepatitis B surface antigen (HBsAg) 1
• Hepatitis C antibody 1
• Immunoglobulin G (IgG) and autoantibodies (ANA, ASMA, anti-LKM) 1
• Anti-mitochondrial antibody 1
• Ferritin and transferrin saturation 1

Determine the pattern of enzyme elevation (AST/ALT ratio, hepatocellular vs. cholestatic) to guide further testing 2.

Age and Weight-Specific Considerations

Very Young or Non-Overweight Children

Test for monogenic causes of chronic liver disease 1:

• Fatty acid oxidation defects 1
• Carnitine metabolism disorders 1
• Peroxisomal disorders 1
• Lysosomal storage diseases 1
• Wilson's disease 1
• Cystic fibrosis 1

Overweight/Obese Children

Consider non-alcoholic fatty liver disease (NAFLD) as a primary differential 1. While formal screening recommendations cannot be made due to limited evidence, some expert committees suggest biannual screening with liver enzymes starting at age 10 years in obese children 1.

Autoantibody Interpretation

Low serum titers of autoantibodies are common in children with NAFLD and do not necessarily indicate autoimmune hepatitis 1. However, higher titers, particularly with markedly elevated aminotransferases and elevated globulin, should prompt liver biopsy to evaluate for autoimmune hepatitis 1.

When to Perform Liver Biopsy

Liver biopsy should be performed in children when 1:

• Diagnosis remains unclear after non-invasive testing 1, 2
• Multiple diagnoses are possible (e.g., distinguishing NAFLD from autoimmune hepatitis) 1
• Before starting potentially hepatotoxic medications 1
• Before initiating pharmacologic therapy for NASH 1

Avoid unnecessary liver biopsy unless it will change management 2. The decision must weigh procedural risks against diagnostic benefit 1.

Specific Disease Considerations

Chronic Hepatitis B

If HBsAg positive, monitor ALT and HBeAg/anti-HBe every 6 months 2. Liver biopsy is recommended in most children with compensated liver disease prior to therapy 1. Treatment is indicated for moderate to severe necroinflammation and/or more than mild portal fibrosis 1.

NAFLD

Pathologists should recognize the unique pediatric NAFLD pattern (marked macrovesicular steatosis, portal inflammation, and portal fibrosis) to avoid misdiagnosis 1. Histology in children can differ substantially from adult patterns 1.

Follow-Up Strategy

Do not simply repeat the same panel of tests without determining the cause 1. In adults, 84% of abnormal liver tests remain abnormal at 1 month, and 75% at 2 years 1.

For identified chronic liver disease, annual monitoring is recommended 2. For viral hepatitis, monitor liver function tests every 3 months during acute phase, then at least yearly during follow-up 3.

Common Pitfalls to Avoid

• Do not assume transient elevation without investigation – most abnormalities persist and warrant etiologic workup 1
• Do not overlook extrahepatic causes including muscle injury, cardiovascular disease, and medications 1
• Do not misinterpret isolated elevated ferritin as hemochromatosis – this commonly reflects dysmetabolic iron overload in NAFLD or alcohol excess 1
• Do not delay referral in children – the threshold for specialist consultation should be lower than in adults 1