What are liver function tests?

Liver Function Tests: Overview

Liver function tests (LFTs) are a panel of biochemical blood tests that primarily measure hepatocellular injury and cholestasis rather than actual liver function, with true functional assessment requiring measurement of synthetic capacity (albumin, INR) and metabolic clearance. 1

What LFTs Actually Measure

The term "liver function tests" is a misnomer because most components measure hepatobiliary injury patterns, not functional capacity 1, 2:

Tests of Hepatocellular Injury (Not Function)

• ALT (Alanine Aminotransferase): Most specific for liver injury due to low concentrations in other tissues; normal values are 29-33 IU/L in men and 19-25 IU/L in women 1
• AST (Aspartate Aminotransferase): Less specific than ALT as it's also present in heart, skeletal muscle, kidneys, brain, and red blood cells 1
• ALP (Alkaline Phosphatase): Elevated in cholestatic liver disease; requires GGT confirmation for hepatic origin 1
• GGT (Gamma-Glutamyl Transpeptidase): Confirms hepatic origin of elevated ALP 1

Tests of Actual Liver Function

• Bilirubin: Measures excretory function; conjugated vs. unconjugated fractions distinguish causes 1
• Albumin: Reflects hepatic synthetic capacity, though reduced in many non-hepatic conditions (sepsis, nephrotic syndrome, malabsorption) 1
• INR/Prothrombin Time: Measures synthesis of clotting factors (II, V, VII, IX, X); prolonged when >70% of synthetic function is lost 1
• Platelet Count: Indicator of advanced fibrosis and portal hypertension 1

Standard vs. Extended Panels

A standard LFT panel should minimally include ALT and ALP, as these identify the vast majority of adults with liver disease 1:

Standard Panel Components 1

• ALT and AST (hepatocellular pattern)
• ALP and GGT (cholestatic pattern)
• Total bilirubin
• Albumin
• INR/PT
• Platelet count

Extended Aetiology Panel (When Abnormal) 1

• Viral hepatitis: Hepatitis B surface antigen, hepatitis C antibody with PCR if positive
• Iron overload: Ferritin and transferrin saturation
• Autoimmune: Anti-mitochondrial antibody, anti-smooth muscle antibody, ANA, immunoglobulins
• Metabolic: Alpha-1-antitrypsin, thyroid function

Interpretation Patterns

Hepatocellular Pattern 1

• Predominant elevation of aminotransferases (ALT/AST) >> ALP
• Severity classification:
  • Mild: <5× upper reference limit
  • Moderate: 5-10× upper reference limit
  • Severe: >10× upper reference limit 1
• AST:ALT ratio >2 suggests alcohol-induced disease; <1 suggests metabolic/NAFLD 1

Cholestatic Pattern 1

• Predominant elevation of ALP ± bilirubin >> aminotransferases
• Requires GGT to confirm hepatic origin of ALP 1
• Abdominal ultrasound essential to distinguish extrahepatic (biliary obstruction) from intrahepatic cholestasis 3

Isolated Hyperbilirubinemia 1

• Unconjugated (indirect): Hemolysis or Gilbert's syndrome (most common cause of isolated elevated bilirubin) 1
• Conjugated (direct) >25 μmol/L in neonates: Requires urgent pediatric referral 1

Critical Limitations

LFTs used in isolation are neither specific diagnostic tools nor effective exclusion tools for significant liver disease 1:

• 30% of routine LFTs show at least one abnormal value outside reference range 1
• Only 3.9% of patients with abnormal ALT/AST are diagnosed with significant liver disease within 5 years 1
• Most patients referred with abnormal LFTs have no evidence of significant liver disease 1
• In fatty liver disease, enzyme levels do not correlate with fibrosis stage 1

Fibrosis Assessment Required

When LFTs are abnormal without clear acute cause, fibrosis risk stratification is essential using validated scores 1:

• FIB-4 score <1.3 or NAFLD Fibrosis Score ≤-1.455 indicates low risk of advanced fibrosis 1
• For patients >65 years, use higher cut-offs: FIB-4 <2.0 1
• Second-line tests include Enhanced Liver Fibrosis (ELF) score and elastography (FibroScan, ARFI) 1

Common Pitfalls

• Do not assume normal LFTs exclude liver disease: Liver disease develops silently; tests may be normal until complications of liver failure or portal hypertension develop 1
• Do not over-interpret albumin as liver-specific: Multiple non-hepatic conditions cause hypoalbuminemia 1
• Do not ignore the pattern: Hepatocellular vs. cholestatic patterns guide differential diagnosis more than absolute values 1
• In leptospirosis, expect disproportionately high bilirubin with only mild transaminase elevation—severe transaminase elevation (>10× ULN) suggests alternative diagnoses 4