• Common tests used to evaluate liver function & diagnose liver disease include liver enzymes (AST, ALT, ALP), bilirubin (total, direct, indirect), and liver synthetic function tests (albumin, PT/INR).
AST (aspartate aminotransferase): transfers amino groups from aspartate to α-ketoglutarate (part of citric acid cycle), found in cytoplasm & mitochondria, diffusely in hepatocytes (hence a surrogate for hepatocellular injury), heart, skeletal muscle, kidneys, brain, red blood cells, pancreas
ALT (alanine aminotransferase): transfers amino groups from alanine to α-ketoglutarate (part of citric acid cycle), found in cytoplasm, primarily in hepatocytes (hence a surrogate for hepatocellular injury), very little in kidneys, skeletal muscle
ALP (alkaline phosphatase): enzyme transporting metabolites across cell membranes, found primarily in bile duct epithelia (hence a surrogate for cholestasis) and bone, also in placenta, kidneys, intestines, leukocytes
GGT (gamma-glutamyl transpeptidase): microsomal enzyme transporting amino acid across cell membranes, found in both hepatocytes and bile duct epithelia, also in kidneys, pancreas, intestine
Bilirubin: a product of heme metabolism
Direct (conjugated): excreted from the liver down and travels the biliary tree
Indirect (unconjugated): released from red blood cells
Albumin: protein produced by the liver, carried important organic molecules in the blood
PT/INR: a measure of clotting factors produced by the liver
• The combinations of various liver function test values can suggest different patterns of liver pathology
Hepatocellular: damage to the hepatocytes leading markedly increased levels of aminotransferases (ALT, AST) with or without increased levels of ALP and bilirubin (due to the affected intrahepatic biliary structure).
Cholestatic: damage to the bile duct epithelia in either or both intra- and extra-hepatic regions (liver parenchyma and biliary tree) leading to increased level of ALP (found in bile duct epithelia) and of bilirubin (a marker of bile flow).
Infiltrative: deposition of organic substrates in the liver often causing isolated ALP level.
• The level and ratio of AST and ALT vary in different liver conditions hence can be used as diagnostic clues.
• Aminotransferases are markedly elevated in acute/ fulminant liver injury caused by ischemia, drug/ toxin (acetaminophen, mushroom poisoning), and viral hepatitis; and to a lesser degree, alcohol abuse, autoimmune hepatitis, Wilson disease, and HELLP syndrome.
• Aminotransferases are mildly elevated in chronic liver conditions that are well-compensated; however, albumin is often low in chronic states.
• ALT is often higher than AST in most liver diseases except for acute ischemic/ toxic hepatitis, alcoholic liver disease, cirrhosis, and WIlson disease.
• Elevated PT/INR is a marker of declined liver synthetic function and is often seen in acute fulminant liver failure and end-stage liver disease such as cirrhosis.
• GGT is a useful marker to confirm alcoholic iiver disease.
