Liver Function Test Analysis

Aminotransferases in general (AST, ALT) (Transaminitis)
- 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)
- ALPprimarily associated with cholestasis and malignant hepatic infiltration
  - Marker of rapid bone turnover and extensive bony metastasis
- GGTsensitive to alcohol ingestion
  - Marker of Hepatocellular damage but non-specific
  - Sharpest rise associated with biliary and hepatic obstruction

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
  - 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 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

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, isoniasid, nitrofurantoin
- Morphine, codeine (Increasing intrabiliary pressure) (AST and ALT)

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 cannalicular 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
  - Pagets disease
  - Deficiency induced Ricket’s
  - 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 metastasi – 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) is associated with transfer of amino acids across cell membranes
It 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) catalyses the reversible conversion of lactic acid to pyruvic acid. The final step in Embden-Meyerhoff pathway, providing bridge to Krebs cycle and thus cellular energy
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
LDH is most useful in monitoring injury heart, liver, lung, hematological disorders
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

Liver Function Tests