How do you interpret liver function tests, including Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT) levels?

How to Interpret Liver Function Tests

Initial liver disease investigation should include bilirubin, albumin, ALT, ALP, and GGT, with ALT being the most specific marker for hepatocellular injury. 1

Essential Components of the Initial Panel

The streamlined approach to liver function testing prioritizes sensitivity without generating excessive false positives:

• Bilirubin assesses cholestasis and synthetic function 1
• Albumin evaluates synthetic capacity and chronic liver disease severity 1
• ALT (Alanine Aminotransferase) is the most liver-specific enzyme, with minimal presence in cardiac muscle, skeletal muscle, kidney, and red blood cells 2
• ALP (Alkaline Phosphatase) primarily indicates cholestatic disorders but can be elevated in bone diseases 2
• GGT (Gamma-Glutamyl Transferase) helps confirm hepatic origin of ALP elevation 1
• Full blood count should be included if not performed within the previous 12 months 1

Understanding ALT vs AST

ALT is more specific for liver injury than AST, which can be elevated from non-hepatic sources 2, 3:

• ALT specificity: Primarily concentrated in liver tissue, making elevations highly indicative of hepatocellular damage 2
• AST limitations: Present in cardiac muscle, skeletal muscle, kidney, and erythrocytes, reducing its specificity for liver disease 2, 3
• Normal reference ranges differ by sex: Males 29-33 IU/L, Females 19-25 IU/L 2

When to Add AST to the Panel

While routine addition of AST to initial testing does not improve disease detection 1, calculating AST after detecting abnormal ALT or GGT is valuable for assessing fibrosis risk:

• AST:ALT ratio >1 indicates advanced fibrosis or cirrhosis in adults with nonalcoholic liver disease 1, 4
• AST:ALT ratio <1 is characteristic of NAFLD, viral hepatitis, or medication-induced injury 2
• AST:ALT ratio >2 suggests alcoholic liver disease 4
• This ratio maintains utility even when both values are within normal reference intervals 1

Important caveat: The AST:ALT ratio becomes less reliable in distinguishing alcoholic from nonalcoholic liver disease when cirrhosis is present 4

Severity Classification of Transaminase Elevations

Understanding the magnitude of elevation guides urgency and management 2:

• Mild elevation: <5× upper limit of normal (ULN)
• Moderate elevation: 5-10× ULN
• Severe elevation: >10× ULN

Critical thresholds for action 2:

• ALT >5× ULN warrants hepatology referral
• ALT ≥3× ULN with bilirubin >2× ULN indicates severe hepatocellular injury requiring urgent evaluation

Pattern Recognition: Hepatocellular vs Cholestatic

Calculate the R ratio to distinguish injury patterns 5:

R = (ALT/ULN) ÷ (ALP/ULN)

• R ≥5: Hepatocellular pattern (viral hepatitis, NAFLD, drug-induced injury, ischemic hepatitis)
• R <2: Cholestatic pattern (biliary obstruction, primary biliary cholangitis, drug-induced cholestasis)
• R 2-5: Mixed pattern

Critical Pitfalls to Avoid

Normal liver tests do not exclude advanced liver disease 6:

• Both AST and ALT can be normal even in cirrhosis 1
• Up to 10% of patients with advanced fibrosis may have normal ALT using conventional thresholds 2
• Albumin, INR, and platelet count provide additional information about synthetic function and portal hypertension 6

Non-hepatic causes of transaminase elevation must be excluded 2, 7:

• Muscle injury: Check creatine kinase if recent exercise or trauma
• Cardiac injury: AST rises disproportionately in myocardial infarction
• Hemolysis: Can elevate AST
• Thyroid disorders: Check TSH in unexplained elevations
• Medications: Review all prescriptions, over-the-counter drugs, and supplements

Algorithmic Approach to Abnormal Results

Step 1: Confirm and Characterize

• Repeat testing in 2-4 weeks to establish trend 2
• Calculate R ratio to determine pattern 5
• Calculate AST:ALT ratio if both available 1

Step 2: Initial Diagnostic Workup

For hepatocellular pattern (R ≥5) 2:

• Viral hepatitis serologies (HBsAg, anti-HCV, anti-HBc)
• Detailed alcohol history
• Complete medication review including supplements
• Assess metabolic syndrome components (obesity, diabetes, hypertension)
• Abdominal ultrasound (sensitivity 84.8%, specificity 93.6% for moderate-severe steatosis)

For cholestatic pattern (R <2) 1:

• Abdominal ultrasound to assess biliary tree
• Consider autoimmune markers if ALP and GGT elevated

Step 3: Risk Stratification for Fibrosis

AST:ALT ratio >1 suggests advanced fibrosis and warrants 1, 4:

• FIB-4 score calculation (if >2.67, high risk for advanced fibrosis)
• Consider hepatology referral
• Possible transient elastography

Step 4: Monitoring Strategy

For mild elevations (<2× ULN) 2:

• Repeat in 4-8 weeks until stabilized or normalized
• Address modifiable risk factors (alcohol, medications, weight)

For moderate elevations (2-5× ULN) 2:

• Repeat within 2-5 days
• Intensify diagnostic evaluation
• Consider hepatology consultation if persistent >6 months

For severe elevations (>5× ULN) 2:

• Urgent evaluation within 2-3 days
• Immediate hepatology referral
• Complete liver panel including INR to assess synthetic function

Special Populations

High-risk groups may warrant simultaneous second-line testing 1:

• Injecting drug users
• Migrants from high-prevalence areas for viral hepatitis
• Prisoners
• Patients with pre-existing autoimmune diseases

Pediatric patients: Non-invasive fibrosis markers have not been sufficiently validated and should not be routinely applied 1