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Interpretation of liver function tests


  • Acute hepatitic picture: ALT/AST in 1000s, ALP mildly raised
  • Chronic hepatitic picture: ALT/AST in 100s
  • Cholestatic (obstructive) picture: ALP significantly raised, ALT/AST mildly raised, ↑bilirubin
  • Alcoholic: ↑γGT, ↑mean corpuscular volume, AST/ALT mildly elevated (AST>ALT), ↑bilirubin in acute alcoholic hepatitis (may be disproportionate to ALT/AST)
  • Cirrhosis/chronic liver disease: liver enzymes may be normal, ↓albumin, ↑coagulation tests

Liver enzymes

Enzymes leak from damaged liver cells and therefore they reflect liver injury (not function).

Aminotransferases – alanine aminotransferase (ALT) and aspartate aminotransferase (AST)

  • ALT sources: specific to liver
  • AST sources: liver, heart, skeletal muscle, kidneys, pancreas
  • Marked increase (>1000): 
    • Toxin-/drug-induced hepatitis (e.g. paracetamol)
    • Acute viral hepatitis (Hep A/B/E, EBV, CMV)
    • Liver ischaemia
  • Modest increase (300-500): chronic viral/alcoholic/autoimmune hepatitis, biliary obstruction
  • Mild increase (<300): cirrhosis, non-alcoholic fatty liver disease, hepatocellular carcinoma, haemochromatosis/Wilson’s, cardiac
  • Ratio of ALT:AST
    • ALT>AST: chronic liver disease
    • AST>ALT: + in established cirrhosis, ++ in alcoholic liver disease

Alkaline phosphatase (ALP)

  • Main sources: biliary ducts, bone (Paget’s disease, bony metastasis, fractures, osteomalacia, renal bone disease)
  • Lesser sources: placenta (pregnancy), small intestine (fatty meals), kidneys (chronic kidney disease)
  • isoenzyme analysis can confirm

Marked increase (>4x normal): cholestasis (e.g. gallstones, pancreatic cancer, primary biliary cholangitis, primary sclerosing cholangitis, drugs, strictures)

  • Moderate increase (<3x normal): hepatitis, cirrhosis, infiltration (e.g. hepatocellular carcinoma, liver abscess etc.)

Gamma-glutamyltransferase (γGT)

  • Mirrors ALP so can be used to confirm if a rise in ALP is of hepatic origin
  • Raised with alcohol abuse and enzyme-inducing drugs


Extravascular haemolysis results in breakdown of Hb → globulin (further broken down into amino acids) + haem (further broken down into bilirubin). This unconjugated bilirubin is then conjugated by the liver so it can be excreted in bile. In advanced liver disease, the liver retains its ability to conjugate bilirubin, but it cannot excrete it.

Normal bilirubin values (µmol/L)
Total  ≤20
Indirect (unconjugated)  ≤15
Direct (conjugated)  ≤5
  • Unconjugated hyperbilirubinaemia: increased ‘indirect’ bilirubin (unconjugated = indirect)
    • Increased red blood cell breakdown (haemolytic anaemia)
    • Impaired hepatic uptake (drugs, heart failure)
    • Impaired conjugation (Gilbert’s syndrome, physiological neonatal jaundice)
  • Mixed hyperbilirubinaemia
    • Hepatocellular dysfunction (liver disease)
  • Conjugated hyperbilirubinaemia: increased ‘direct’ bilirubin (direct = directly related to the liver)
    • Biliary obstruction (cholestasis)

Functional liver tests


Albumin makes up more than half of the total protein in the blood. The remainder is made up by globulins (other blood proteins) which include α1-globulins (α1-antitrypsin), α2-globulins (α2-macroglobulin, haptoglobin), β-globulins (complement, transferrin), and γ-globulins (immunoglobulins). Albumin is synthesised by the liver and has a half-life of around 20 days. Hence, changes in levels happen over weeks.

  • ↓albumin + ↓total protein = cirrhosis, nephrotic syndrome, chronic inflammation, protein-losing enteropathy, alcoholism, protein malnutrition/malabsorption
  • ↓albumin + normal total protein = infection (albumin is a negative acute phase protein)
  • ↓albumin + ↑ total protein = myeloma, Waldenström’s macroglobulinaemia, autoimmune conditions, infection, chronic inflammation

Prothrombin time/INR

PT/INR depend on clotting factors and fibrinogen which are synthesised by the liver. Some clotting factors have short half-lives (e.g. 6-8 hours) so changes can occur rapidly.

  • Raised PT/INR: liver disease (with impaired function), vitamin K deficiency, consumptive coagulopathy (e.g. disseminated intravascular coagulation)

Other tests

FBC clues

  • Anaemia = GI bleeding
  • Macrocytosis = alcohol
  • Thrombocytopenia = effect of alcohol on bone marrow, hypersplenism, liver cirrhosis or disseminated intravascular coagulation

Further investigations to find cause

Blood tests

  • Viral
    • Viral hepatitides: hepatitis A IgM, hepatitis B surface antigen, hepatitis C IgG, hepatitis E IgM
    • CMV serology
    • EBV serology
  • Autoimmune liver screen
    • Anti-smooth muscle (autoimmune hepatitis type 1)
    • Anti-mitochondrial (primary biliary cholangitis)
    • Anti-liver-kidney microsomal (autoimmune hepatitis type 2, hepatitis C/D, drug-induced hepatitis)
    • Antinuclear (autoimmune hepatitis type 1, SLE)
  • Tumour markers – if cirrhosis/weight loss
    • α- fetoprotein (hepatocellular carcinoma)
  • Infiltrative 
    • Ferritin and transferrin saturation (haemochromatosis) – but be aware ferritin is also an acute phase protein
    • Serum copper and caeruloplasmin ± 24-hour urinary copper (Wilson’s disease)
    • Fasting glucose and lipids (fatty liver disease)
  • Metabolic
    • α1-antitrypsin (α1-antitrypsin deficiency)
    • Immunoglobulins and protein electrophoresis (IgM raised in primary biliary cholangitis, IgA raised in alcoholic liver disease, IgG raised in autoimmune hepatitis)
    • Tissue transglutaminase antibody (coeliac disease)
  • Toxins 
    • Paracetamol level (paracetamol overdose)


  • Abdominal ultrasound: first line imaging (quick and cheap) that is useful for determining liver texture, size and presence of any gallstones or cholecystitis 
  • Abdominal CT: can confirm pancreatitis or tumour
  • Elastography: grades liver fibrosis in chronic liver disease non-invasively 
  • Magnetic resonance cholangiopancreatography: to look for duct disease/stones if ultrasound normal


  • Ascitic tap: if ascites present
  • Liver biopsy (CT-guided usually, but done trans-jugular if there is ascites or coagulopathy)

Some non-hepatic causes of Derranged LFTs

In addition to any described above:

  • Drugs
    • Hepatitis: tuberculosis antibiotics (rifampicin/isoniazid/pyrazinamide), sodium valproate, methotrexate, methyldopa, amiodarone, statins, paracetamol, phenytoin, ketoconazole/fluconazole, nitrofurantoin, sulfonylureas/sulfonamides
    • Cholestasisco-amoxiclav (may be delayed/severe), clarithromycin/erythromycin, carbamazepine, chlorpromazine, contraceptives, flucloxacillin, sulfonylureas/sulfonamides
  • Right heart failure
  • Sepsis
  • Coeliac disease
  • Haemolysis
  • Hyperthyroidism
  • Right lower lobe pneumonia
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