What initial labs should be checked with an elevated Alanine Transaminase (ALT) and a normal Aspartate Transaminase (AST)?

Initial Laboratory Workup for Elevated ALT with Normal AST

For an isolated ALT elevation of 77 IU/L with normal AST, obtain a complete liver panel, viral hepatitis serologies (HBsAg, anti-HCV), metabolic parameters (fasting glucose, lipid panel), and consider abdominal ultrasound to evaluate for the most common cause—nonalcoholic fatty liver disease. 1

Confirm the Elevation First

• Repeat ALT testing within 1-2 weeks to confirm persistence, as a single elevated value may not indicate true liver pathology 2
• If two ALT values differ by >50% and the higher value is >2× upper limit of normal (ULN), perform a third test to determine the direction of change 2
• An ALT of 77 IU/L represents approximately 2-3× ULN for females (normal 19-25 IU/L) or 2-2.5× ULN for males (normal 29-33 IU/L), warranting systematic evaluation 1

Essential Initial Laboratory Tests

Complete Liver Panel

• AST, ALT, alkaline phosphatase, total and direct bilirubin, albumin, and prothrombin time/INR to assess for cholestatic patterns and synthetic liver function 1
• The AST:ALT ratio <1 pattern (normal AST with elevated ALT) is characteristic of NAFLD, viral hepatitis, or medication-induced liver injury 3, 1
• Normal albumin, bilirubin, and PT/INR indicate preserved synthetic function despite hepatocellular injury 1

Viral Hepatitis Serologies

• Hepatitis B surface antigen (HBsAg), hepatitis B core antibody IgM (HBcIgM), and hepatitis C antibody (anti-HCV) should be performed as part of the initial evaluation 1
• Chronic viral hepatitis is a common cause of isolated ALT elevation, and enzyme elevation may not correlate well with degree of liver damage 4

Metabolic Parameters

• Fasting glucose or hemoglobin A1c, lipid panel (triglycerides, cholesterol), and assessment for metabolic syndrome components (obesity, diabetes, hypertension) 1
• NAFLD is the most common cause of isolated ALT elevation in asymptomatic patients, strongly correlated with metabolic syndrome 3, 2
• Hypertriglyceridemia, hypercholesterolemia, and diabetes are frequently associated with elevated ALT 5

Additional Screening Tests

• Thyroid-stimulating hormone (TSH) to rule out hypothyroidism as a cause of transaminase elevation 1
• Creatine kinase (CK) to rule out muscle disorders as a cause of AST elevation if AST becomes elevated on repeat testing 1
• Hypothyroidism and muscle injury are non-hepatic causes that can elevate liver enzymes 4

Risk Factor Assessment

Critical History Elements

• Detailed alcohol consumption history: >14 drinks/week for men or >7 drinks/week for women is significant 1, 2

• Even moderate alcohol consumption can contribute to persistent ALT elevation and impede recovery 1

• Complete medication review: prescription medications, over-the-counter drugs, and herbal supplements can cause drug-induced liver injury 1

• Medication-induced liver injury commonly presents with transaminase elevations and normal synthetic function 1

• Metabolic risk factors: assess for obesity (BMI, waist circumference), diabetes, and hypertension as NAFLD risk factors 3, 1

Initial Imaging

• Abdominal ultrasound is the first-line imaging test with sensitivity of 84.8% and specificity of 93.6% for detecting moderate to severe hepatic steatosis 1
• Ultrasound can identify structural causes including biliary obstruction, focal liver lesions, and other hepatobiliary disorders 1
• Order ultrasound early in the evaluation, particularly if gamma-glutamyl transferase (GGT) is also elevated, suggesting potential cholestatic pattern 1

Advanced Testing for Unclear Cases

If initial workup is unrevealing, consider:

• Iron studies (serum iron, ferritin, transferrin saturation) to evaluate for hemochromatosis 2
• Autoimmune markers (antinuclear antibody, anti-smooth muscle antibody, immunoglobulins) if autoimmune hepatitis is suspected 2
• Alpha-1 antitrypsin level and phenotype for younger patients or those with family history 2
• Ceruloplasmin for Wilson's disease in patients <40 years old 2

Monitoring Strategy Based on Severity

• For ALT 77 IU/L (approximately 2-3× ULN): Repeat testing within 2-5 days and perform comprehensive evaluation as outlined above 1, 2
• If ALT normalizes or decreases, continue monitoring every 4-8 weeks until stabilized 1
• If ALT increases to >3× ULN or bilirubin >2× ULN, more urgent follow-up within 2-3 days is warranted 1
• Consider hepatology referral if transaminases remain elevated for ≥6 months or if there is evidence of synthetic dysfunction 1

Common Pitfalls to Avoid

• Do not rely on a single ALT measurement: ALT values have high visit-to-visit variability, with 43% of HCV-infected patients showing intermittently elevated values 6
• Do not assume normal ALT excludes liver disease: Up to 50% of patients with NAFLD have normal liver chemistries 3
• ALT is more liver-specific than AST: AST can be elevated in cardiac, skeletal muscle, kidney, and red blood cell disorders, making ALT the preferred marker for hepatocellular injury 1, 7
• Sex-specific reference ranges matter: Women have significantly lower normal ALT ranges (19-25 IU/L) than men (29-33 IU/L), making the same absolute value more significant in women 1