Liver Function Tests

Overall analysis of Liver Function Tests (LFT)

Transaminitis: Aminotransferases (AST, ALT)

• Generally associated with hepatocellular damage
• Generally not associated with cholestasis
• Ratio of AST and ALT can be useful in differential
• ALT is more specific for liver damage than AST
• AST: ALT =1
  • Associated with ischaemia (CCF and ischaemic necrosis and hepatitis)
• AST: ALT >2.5
  • Associated with Alcoholic hepatitis
  • Alcohol induced deficiency of pyridoxal phosphate
• AST: ALT <1
  • High rise in ALT specific for Hepatocellular damage
  • Paracetamol OD with hepatocellular necrosis
  • Viral hepatitis, ischaemic necrosis, toxic hepatitis

Elevation with cholestasis (ALP, GGT)

• ALP – primarily associated with cholestasis and malignant hepatic infiltration
  • Marker of rapid bone turnover and extensive bony metastasis
• GGT – sensitive to alcohol ingestion
  • Marker of hepatocellular damage but non-specific
  • Sharpest rise associated with biliary and hepatic obstruction

Aspartate aminotransferase (AST)

Aspartate aminotransferase (AST) catalyses conversion of nitrogenous portion of amino acid. It is essential to energy production in Krebs cycle.

• AST is released into serum in proportion to cellular damage and most elevated in acute phase of cellular necrosis.
• Found in decreasing levels in: (Relatively low organ specificity)
  • Liver, cardiac, skeletal muscle, kidney, brain, pancreas, red blood cells
• Useful in the detection and differential diagnosis of hepatic disease
  • Monitor patients with cardiac and hepatic disease – levels are dependent on stage of disease

AST Levels below are for the peak of disease

• Serum level >20 x normal
  • Severe skeletal muscle trauma
  • Acute viral hepatitis
  • Toxic hepatitis (Drug induced hepatic injury)
  • Ischaemic hepatitis (Severe passive liver congestion (CCF))
• Serum level 10-20 times normal
  • CVS (Severe myocardial infarction)
  • Infection (Infectious mononucleosis)
  • Liver (Alcoholic cirrhosis)
• Serum level 5-10 times normal
  • Liver (Chronic hepatitis)
  • Skeletal muscle
    • Duchenne muscular dystrophy (DMD)
    • dermatomyositis
    • influenza B calf myositis in children
• Serum levels 2-5 times normal
  • blood (haemolytic anaemia, haemolysis)
  • liver (fatty liver, metastatic hepatic tumour)
  • other:
    • pulmonary embolus, alcoholic delirium tremens, acute pancreatitis, IM injection, strenuous physical exercise
  • drugs
    • opiates, erythromycin, sulphonamides, anti-tubercular
    • large doses of paracetamol, aspirin, vitamin A

Alanine aminotransferase (ALT)

Alanine aminotransferase (ALT) catalyses reversible amine group transfer in Krebs cycle.

• Unlike AST, it is mainly in liver cells and is a relatively specific indicator of hepatocellular damage. It is released early in liver damage and remain elevated for weeks

Interpretation of ALT levels

** Levels are NOT related to degree of liver cell necrosis

** Absolute value is of NO prognostic significance

• Very high serum ALT
  • hepatocellular injury
  • usually associated with much lower rise in AST
  • AST: ALT <1
    • Viral hepatitis
    • Severe toxic hepatitis
    • Ischaemic hepatitis (Shock, hypotension, CCF)
• Moderate to high levels of ALT
  • infection – Infectious mononucleosis
  • liver – Chronic hepatitis and intrahepatic cholestasis
  • cardiac –Severe hepatic congestion in cardiac failure
  • other – Acute passage of gallstone
• Slight to moderate increase in ALT
  • usually associated with much higher rise in AST
  • AST: ALT ratio >2.5
  • classically associated with alcoholic liver disease
    • liver: acute hepatocellular injury
    • alcoholic hepatitis
    • active cirrhosis
• Drugs causing elevation in ALT
  • paracetamol overdose (AST and ALT)
  • phenothiazines, chlorpromazine
  • barbiturates
  • tetracycline, isoniazid, nitrofurantoin
  • morphine, codeine (Increasing intrabiliary pressure) (AST and ALT)

Alkaline phosphatase (ALP)

Alkaline phosphatase is actually up to 60 different isoenzymes, collectively measured as ALP. Electrophoresis is required to determine the exact type elevated – especially if isolated elevation

• ALP Influence: Bone calcification and lipid and metabolite transport
• ALP is produced by
  • Bile canalicular membrane of hepatocytes
  • Bone, placenta, small intestine
• Elevated ALP is often associated with biliary obstruction with cholestasis – and usually before a rise in bilirubin

Interpretation of ALP levels

• Causes of an increased ALP
  • Liver (usually indicates cholestasis or obstruction) – Sensitive indicator of mild biliary obstruction
    • Hepatic tumour (SOL)
    • Viral hepatitis
    • Infectious mononucleosis
  • Pregnancy (non-pathological) – Released to serum from placenta in late pregnancy
  • Bone (usually non-pathological in children)
    • osteomalacia
    • bone metastasis
    • Paget’s disease of bone
    • deficiency induced rickets
    • adolescents and children with rapid bone growth
  • Blood type O and B (non-pathological) – released form small intestine after fatty meal
• Commonest causes of a marked rise in ALP
  • Complete biliary obstruction
    • malignancy
    • infection
  • Extensive bone metastases – pancreatic associated with isolated ALP rise (no ALT)
  • Hyperparathyroidism
• Causes of isolated rise in ALP
  • CCF (Often associated with AST and ALT rise)
  • Hodgkin’s
  • IBD
  • Diabetes
  • Hyperthyroidism
• Causes of a low ALP
  • Hypomagnesaemia, HYPOphosphatemia
  • Protein deficiency

Gamma glutamyl transferase (GGT)

Gamma glutamyl transferase (GGT) is associated with transfer of amino acids across cell membranes

• GGT is produced in the renal tubules, liver, biliary tract, pancreas, lymphocytes, brain, testes
• GGT is most useful when looking for hepatocellular damage
  • More sensitive than ALP and AST – but much less specific
  • Particularly sensitive to effects of alcohol on liver
  • Increased production of GGT as ductal enzymosis, with increased enzymes produced in response to hepatocellular damage

Increased levels of serum GGT

• Liver
  • Response to any Hepatocellular injury
  • Following alcohol ingestion (No necessity for Hepatocellular damage)
• Other
  • Pancreatitis, Brain tumours, Renal disease, Prostatic disease
  • Cardiac disease (Increase 5-10 days after AMI)

Rapid increase in GGT

• Obstructive jaundice
• Hepatic metastatic infiltration (usually with obstruction)

Lactate Dehydrogenase (LDH)

Lactate dehydrogenase (LDH) catalyses the reversible conversion of lactic acid to pyruvic acid. The final step in Embden–Meyerhof–Parnas pathway, providing bridge to Krebs cycle and thus cellular energy

• LDH is most useful in monitoring injury heart, liver, lung, hematological disorders
• It is found in most body tissues and includes 5 main isoenzymes which can be helpful diagnostically
  • LD1 and LD2 – Heart, RBC, kidneys
  • LD3 – Lungs
  • LD4 and LD5 – Liver and skeletal muscle

Increased LDH

• CVS (LD 1 and 2) – AMI +/- hepatic congestion
  • Rheumatic carditis, Myocarditis, CCF, Shock
• Respiratory (LD3)
  • Pulmonary embolus and infarction
• Haematological (LD 1 and 2)
  • Pernicious anaemia, Haemolytic anaemia, Sickle cell anaemia
• Hepatobiliary (LD5)
  • Hepatitis, Active cirrhosis, Hepatic congestion

References:

• American Family Physician
• How to investigate mildly elevated LFT

CCC Differential Diagnosis Series
NEURO	Anosmia, Ataxia, Blepharospasm, Bulbar and Pseudobulbar palsy, Central Pontine Myelinosis, Cerebellar Disease, Chorea, Cranial nerve lesions, Dementia, Dystonia, Exophthalmos, Eye trauma, Facial twitches, Fixed dilated pupil, Horner syndrome, Loss of vision, Meningism, Movement disorders, Optic disc abnormality, Parkinsonism, Peripheral neuropathy, Radiculopathy, Red eye, Retinal Haemorrhage, Seizures, Sudden severe headache, Tremor, Tunnel vision
RESP	Bronchial breath sounds, Bronchiectasis, High airway pressures, Massive haemoptysis, Sore throat, Tracheal displacement
CVS	Atrial Fibrillation, Bradycardia, Cardiac Failure, Chest Pain, Murmurs, Post-resuscitation syndrome, Pulseless Electrical Activity (PEA), Pulsus Paradoxus, Shock, Supraventricular tachycardia (SVT), Tachycardia, VT and VF, SVC Obstruction
GIT	Abdominal distension, Abdominal mass, Abdominal pain, Asterixis, Dysphagia, Hepatomegaly, Hepatosplenomegaly, Large bowel obstruction, Liver palpation abnormalities, Lower GI haemorrhage, Malabsorption, Medical causes of abdominal pain, Rectal mass, Small bowel obstruction, Upper GI Haemorrhage
GUT	Genital ulcers, Groin lump, Scrotal mass, Urine colour, Urine Odour, Urine transparency,
MSK	Arthritis, Shoulder pain, Wasting of the small muscles of the hand
DERM	Palmar erythema, Serious skin signs in sick patients, Thickened Tethered Skin, Leg ulcers, Skin Tumour, Acanthosis Nigricans
ENDO	Diabetes Insipidus, Diffuse Goitre, Gynaecomastia, Hirsutism, Hypoglycaemia, SIADH, Weight Loss
HAEM	Splenomegaly
PAEDS	Floppy infant
MISC	Anaphylaxis, Autoimmune associated diseases, Clubbing, Parotid Swelling, Splinter haemorrhages, Toxic agents and abnormal vitals, Toxicological causes of cardiac arrest
IMAGING	CHEST: Atelectasis, Hilar adenopathy, Hilar enlargement on CXR, Honeycomb lung, Increased interstitial markings, Mediastinal widening on mobile CXR, Pulmonary fibrosis, Pseudoinfiltrates on CXR, Pulmonary opacities on CXR, ABDO: Gas on abdominal X-ray, Kidney mass, BRAIN: Intracranial calcification, Intracranial structures with contrast, Ventriculomegaly, OTHER: Pseudofracture on X-Ray,
LABS	LOW: Anaemia, Hypocalcaemia, hypochloraemia, Hypomagnesaemia,  HIGH: Bilirubin and Jaundice, Hyperammonaemia, Hypercalcaemia, Hyperchloraemia, Hyperkalaemia, Hypermagnesaemia,  ACID BASE: Acid base disorders, Resp. acidosis, Resp. alkalosis, Creatinine, CRP, Dipstick Urinalysis, Laboratory Urinalysis, Liver function tests (LFTs), Pleural fluid analysis, Urea, Urea Creatinine Ratio, Uric acid, Urinalysis, Urine Electrolytes

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