What is the initial workup for a pediatric patient with transaminitis (elevated liver enzymes)?

Initial Workup for Pediatric Transaminitis

Begin with a focused history targeting medication exposure (including over-the-counter drugs and supplements), viral illness symptoms, family history of liver disease or hepatocellular carcinoma, and assessment for signs of chronic liver disease such as jaundice, hepatosplenomegaly, or ascites. 1

Immediate Assessment

History and Physical Examination

• Obtain detailed medication history including acetaminophen, antibiotics, anticonvulsants, and herbal supplements, as drug-induced liver injury is a common cause 1
• Assess for viral prodrome including fever, fatigue, abdominal pain, and recent exposures 1
• Evaluate for autoimmune symptoms such as arthralgia, rash, or other systemic manifestations 2
• Document family history of liver disease, hepatocellular carcinoma, or metabolic disorders 3
• Perform thorough physical examination looking for hepatomegaly, splenomegaly, jaundice, ascites, or stigmata of chronic liver disease 1

Red Flags Requiring Urgent Specialist Referral

• Coagulopathy (elevated INR/PT) suggesting acute liver failure 3
• Hypoglycemia indicating severe hepatic dysfunction 3
• Encephalopathy or altered mental status 3
• Ascites or signs of portal hypertension 3
• Conjugated hyperbilirubinemia in infants, which may indicate serious conditions like biliary atresia 3

Initial Laboratory Workup

First-Tier Testing

• Complete blood count to assess for thrombocytopenia (suggesting cirrhosis or hypersplenism) and anemia 4
• Comprehensive metabolic panel including ALT, AST, alkaline phosphatase, GGT, total and direct bilirubin, albumin, and glucose 3, 4
• Prothrombin time/INR to assess synthetic liver function 4
• Determine pattern of elevation: AST/ALT ratio <1 suggests non-alcoholic liver disease, while hepatocellular pattern (ALT/AST predominance) differs from cholestatic pattern (alkaline phosphatase/GGT predominance) 4

Second-Tier Testing (Based on Initial Results)

• Viral hepatitis serologies: Hepatitis A IgM, Hepatitis B surface antigen and core antibody, Hepatitis C antibody 3, 4
• Autoimmune markers: ANA, anti-smooth muscle antibody, anti-LKM antibody, immunoglobulin levels if autoimmune hepatitis suspected 4, 2
• Metabolic screening: Ceruloplasmin and 24-hour urine copper (Wilson disease), alpha-1 antitrypsin level and phenotype, fasting lipid panel 3, 4
• Celiac serologies: Tissue transglutaminase antibodies, as celiac disease can cause transaminitis 1

Imaging Studies

• Abdominal ultrasound as initial imaging modality to evaluate liver parenchyma, biliary tract, splenomegaly, and assess for steatosis 4, 1
• Avoid CT scanning unless trauma-related or specific indication, to minimize radiation exposure 5, 6

Management Based on Severity

Mild Elevation (ALT/AST <2x Upper Limit Normal)

• Repeat testing in 2-5 days to establish trend and rule out transient elevation 4
• Continue monitoring every 3-6 months if persistently mildly elevated 3
• Consider observation without extensive workup if patient is asymptomatic and initial screening is negative 1

Moderate Elevation (ALT/AST 2-5x Upper Limit Normal)

• Complete full diagnostic workup as outlined above 4
• Monitor every 3 months if hepatitis B related 3
• Refer to pediatric gastroenterology if elevation persists beyond 6 months or etiology unclear 4, 1

Severe Elevation (ALT/AST >5x Upper Limit Normal or >500 IU/L)

• Immediate comprehensive workup including all viral, autoimmune, and metabolic testing 4
• Urgent pediatric gastroenterology/hepatology consultation 1
• Consider hospital admission if signs of liver failure present 3
• Evaluate for acute viral hepatitis, drug-induced liver injury, or ischemic hepatitis as most common causes 7

Special Considerations

Chronic Hepatitis B Context

• Monitor ALT and HBeAg/anti-HBe every 6 months in known chronic hepatitis B patients 3
• Consider treatment if ALT >1.5x ULN or >60 IU/L (whichever is lower) for at least 6 months with HBV DNA >2000 IU/ml 3
• Perform liver biopsy before treatment initiation to assess inflammation and fibrosis stage 3

Type 2 Diabetes Patients

• Screen for non-alcoholic fatty liver disease at diagnosis and annually with AST/ALT measurement 3
• Refer to gastroenterology for persistently elevated or worsening transaminases 3

Medication-Related Monitoring

• For methotrexate use: Check liver enzymes at least 4-6 days after dosing to avoid misinterpreting transient elevations 3
• Hepatotoxic drugs should be used with caution but are not absolutely contraindicated in children with chronic liver disease 3

Follow-Up Strategy

• Establish baseline with repeat testing if initial elevation is isolated 4
• Refer to specialist if transaminitis persists beyond initial workup or worsens 4, 1
• Annual monitoring for patients with identified chronic liver disease 3
• Avoid unnecessary liver biopsy in children unless diagnosis remains unclear after non-invasive testing or treatment decisions require histologic confirmation 3