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