Liver Function Tests

Overall analysis of LFT

  • 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)

  • 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 (ALT)

  • 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

  • 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, isoniasid, 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 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)

  • 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)

  • 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

 

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