Liver Function Testing

Question 1

Liver (introduction)

Answer 1

• major site of intermediary metabolism and synthesis of many important compounds (carbohydrates, lipids, proteins)
• detoxification of natural and toxic foreign substances
• only organ that can regenerate itself

Question 2

Hepatocyte damage (introduction)

Answer 2

• causes release of intracellular constituents into bloodstream
• therefore measuring plasma enzyme levels determines damage and extent

Question 3

ALT and AST (introduction)

Answer 3

• alanine aminotransferase (ALT)
• aspartate aminotransferase (AST)
• raised levels found in damaged liver cells
• AST present in mitochondria and cytoplasm, ALT only in cytoplasm
• partial cell damage: ALT > AST
• whole cell damage: AST > ALT

Question 4

ALT estimation (introduction)

Answer 4

• catalyses transfer of a-amino group from L-alanine to a-ketoglutarate
• leads to generation of glutamate and pyruvate
• pyruvate with 2,4-dinitrophenylhydrazine to produce coloured hydrazone
• measured at 546nm

Question 5

AST estimation (introduction)

Answer 5

• catalyses transfer of a-amino group from L-aspartate to a-ketoglutarate
• generates glutamate and oxaloacetate
• oxaloacetate with 2,4-dinitrophenylhydrazine to produce coloured hydrazone
• measured at 546nm

Question 6

ALT and ALT levels (results)

Answer 6

• normal ALT: 5-40 U/L
• normal AST: 5-45 U/L
• alcoholic liver disease: both AST+ALT elevated with AST/ALT ratio >2
• non-alcoholic liver disease: both AST+ALT elevated with AST/ALT ratio <1

Question 7

Caveats of liver function tests (results)

Answer 7

• AST isn’t specific to hepatocyte damage, can be raised due to myocardial infarction
• ALT is specific to hepatocyte damage
• non-hepatic causes of elevated AST+ALT: coeliac disease, haemolysis, hyperthyroidism

Question 8

Alcohol-related liver disease ARLD (results)

Answer 8

• liver damage caused by alcohol intake
• symptoms: often none, fat build up inside liver cells (enlarges liver, causing abdominal pain on right side, weight loss, tiredness and weakness)
• greater risk for liver cancer,, lead to cirrhosis

Question 9

Non-alcoholic fatty liver disease NAFLD (results)

Answer 9

• too much fat stored in liver cells
• symptoms: usually none, may include fatigue, pain/discomfort in upper right abdomen
• main complication is cirrhosis, could lead to liver cancer or end-stage liver failure

Question 10

Alkaline phosphatase ALP (other liver enzymes)

Answer 10

• pathological increase in activity seen in cholestatic liver disease + bone disease
• 2 types of tests: general ALP test (blood test; comprehensive metabolic panel, liver panel), isoenzyme test (differentiate between types of ALP, determine tissue of origin, e.g electrophoresis and heat activation)
• cholestatic liver disease: flow of bile from your liver is reduced or blocked

Question 11

G-glutamyl transferase GGT (other liver enzymes)

Answer 11

• plasma activity is frequently very high in alcoholic liver disease
• elevated levels in absence of liver disease in those taking anticonvulsant drugs for treatment of TB (this is enzyme induction). GGT increase isn’t due to cell damage but to increase in production within cells
• measurement of plasma activity provides sensitive indicator of hepatobiliary disease, although its of no value in distinguishing between cholestatic and hepatocellular disease