Liver Function Tests

Liver function tests are a panel consisting of most of:

Bilirubin
End product of haeme metabolism. It is conjugated in the liver, so we can measure:
- Unconjugated bilirubin
  ↑ Indicates either ↑ bilirubin production or ↓ hepatic conjugation.
- Conjugated bilirubin
  ↑ Indicates normal hepatic conjugation and failure of secretion.
γ-Glutamyl transferase (GGT)
Inducible enzyme produced predominantly in the biliary tract. Highly non-specific.
Alkaline Phosphatase (ALP)
Ubiquitous enzyme, found predominantly in on the surface of bile canaliculi, bone (during formation), intestine, and placenta.
Aspartate Aminotransferase (AST)
Kreb cycle enzyme, present in many tissues but most concentrated in:
- Hepatocytes
- Muscle
  ↑ In rhabdomyolysis and MI.
Alanine Transaminase (ALT)
Kreb cycle enzyme, used to turn alanine into pyruvate. Present in (essentially) all cells, but abundant in hepatocytes. ALT is:
- Released after AST
- Rises higher and longer than AST
- Usually lower if alcohol is the cause
Albumin
Hepatically synthesised plasma protein, half-life of ~20 days.
Total protein
Sum of all plasma proteins (not all hepatically synthesised), including: albumin, immunoglobulins, and carrier proteins.

Interpretation

Interpretation of Liver Function Tests
Pattern	Presentation	Causes
Cholestatic	ALP >200 ALP >3× AST ↑ GGT	Hepatic: Cholestasis of pregnancy Primary biliary cirrhosis Primary sclerosing cholangitis Hepatitis Drug toxicity Malignancy Extrahepatic: Choledocholithiasis Cholangitis Pancreatitis
Hepatitic	ALT >200 ALT >3× ALP	Circulatory: Right heart failure Ischaemic hepatitis ↑ Venous pressures Metabolic: Haemochromatosis Wilson’s disease α1-antitrypsin deficiency GI: Fatty liver NASH Pancreatitis Trauma: Surgical Hepatic injury Infective: Viral hepatitis Toxin: Alcohol Paracetamol Mushrooms Amanita phalloides. Obstetric: Cholestasis of pregnancy Congenital: Glycogen storage disease
	ALT >> AST	Hepatic: Alcoholic toxicity/hepatitis Early hepatic ischaemia Extrahepatic: Rhabdomyolysis MI
	AST >> ALT	Viral Drugs
Bilirubin	↑ Unconjugated	↑ Production: Haemolysis Transfusion Resorption (haematomas, UGIB) ↓ Uptake: Gilbert’s syndrome Drugs ↓ Conjugation: Gilbert’s syndrome Physiological jaundice of the newborn
	↑ Conjugated	Biliary obstruction Failure to excrete Syndromal.
Other	Isolated ↑ GGT	MI Myocarditis COPD Diabetes Renal failure Drugs: * Alcohol * Phenytoin * Flucloxacillin * Barbiturates
	↑ ALP	Physiological: 3^rd trimester Children/adolescents Familial Hepatic: Obstruction Primary biliary cirrhosis Primary sclerosing cholangitis Cholestasis Metastatic Extra-hepatic: Bone disease Sarcoid Hyperthyroidism

Blood:

Viral hepatitis screen
- Hepatitis A/B/C
- EBV
- CMV
Autoimmune screen
- Anti-mitochondrial antibodies (AMA)
- Antinuclear antibodies (ANA)
- Anti-smooth muscle antibodies (ASMA)
- p-Anti-Neutrophil Cytoplasmic Antibodies (p-ANCA)
α₁-antitrypsin
Infiltrative disease
- Copper
- Ceruloplasmin
- Ferritin
Paracetamol level
Evidence of liver dysfunction
- BSL
- Coagulation profile
  Presence of synthetic dysfunction.
  - ↑ INR if fat-soluble vitamin intake, absorption, or storage are impaired
  - ↑ APTT if synthesis impaired
  - Mixing studies demonstrate reversibility
- Ammonia
Concomitant pancreatic dysfunction
- Amylase
- Lipase

Coagulation testing is covered in detail under Haemostatic Assays.

Radiology:

Liver ultrasound
- Bile duct obstruction
- Hepatic vascular supply
- Hepatic texture

Pathology: