31. Laboratory tests that predict hepatic disorders.
Several liver biochemical tests can be used to evaluate the state of the liver. These are also called liver function tests (LFTs), but this is sort of misleading because the tests do not necessarily reveal how the liver is functioning.
| Parameter | Sample | Reference range |
|---|---|---|
| Total bilirubin | Serum | 5 – 20 µM |
| Albumin | Serum | 35 – 53 g/L |
| Total protein | Serum | 66 – 83 g/L |
| AST | Serum | < 44 U/L |
| ALT | Serum | < 50 U/L |
| Gamma-GT | Serum | < 70 U/L |
| Alkaline phosphatase | Serum | 40 – 130 U/L |
Markers of hepatocellular damage
These are the laboratory tests which reflect injury to the hepatocytes. Significantly elevated ALT and AST is seen in hepatitis of any cause. They may be moderately elevated in cholestasis, liver cancer, and heart failure.
Alanine aminotransferase (ALT)
Alanine aminotransferase (ALT, ALAT), also called glutamate-pyruvate transaminase (GPT) is an enzyme found in the hepatocytes. It's the most commonly used parameter for hepatocellular damage as it's only found in the cytosol of hepatocytes.
Aspartate aminotransferase (AST)
Aspartate aminotransferase (AST, ASAT), also called glutamate-oxaloacetate transaminase (GOT) is an enzyme found in hepatocytes, skeletal muscle, kidney, brain, RBC, and gall bladder. This enzyme is found in the mitochondria and is only released in severe hepatocyte injury, so it's less sensitive than ALT. It's also not specific, as it's also found in other tissues.
In most hepatites, ALT is higher than AST. Notable exceptions where the AST is higher include alcoholic liver disease and cirrhosis. In alcoholic liver disease, the AST is often twice as high as the ALT (the AST/ALT ratio is > 2).
LDH
Lactate dehydrogenase is a general marker of cell injury and is therefore also elevated in hepatocellular damage.
Markers of cholestasis
These laboratory tests reflect cholestasis. They are elevated in cholestasis or other biliary disease like cholangitis, cholecystitis, and choledocholithiasis.
Gamma-glutamyl transpeptidase (GGT)
Gamma-glutamyl transpeptidase (GGT) is an enzyme mainly present in the bile ducts. It's usually significantly elevated in case of biliary disease (5-30 x the upper normal reference limit).
Alkaline phosphatase (ALP)
Alkaline phosphatase (ALP) is a group of enzymes which split phosphate esters in a basic pH, hence the name. It's function is actually not well understood. The enzyme is located in many tissues, including liver, skeletal muscle, large intestine, and osteoblasts. In case of cholestasis, ALP in the bile duct-adjacent hepatocytes increases, which we can measure in the blood. It's not specific for bile duct disease. Significant ALP elevation with a normal GGT indicates bone disease rather than bile disease.
Bilirubin
Main article: Bilirubin
Bilirubin is a breakdown product of haeme in haemoglobin. Unconjugated bilirubin is not water soluble and is therefore bound to albumin in the plasma. When it reaches the liver, hepatocytes conjugate the bilirubin, forming conjugated bilirubin, which is excreted in the bile. Significantly elevated bilirubin (> 40 mol/L) gives jaundice.
In case of cholestasis, conjugated bilirubin in the bile leaks back to the blood. In case of cholestasis, conjugated bilirubin increases. In case of haemolysis, unconjugated bilirubin increases. A mild elevation of unconjugated bilirubin in the absence of signs of liver disease is a hallmark of Gilbert syndrome, a harmless condition.
Markers of hepatic function
There are no specific and sensitive markers of hepatic functions, but some tests can be used to evaluate the liver's synthetic function with some sensitivity and specificity. Bilirubin may be elevated in severe liver failure, but it may be normal as well.
Albumin
Main article: Albumin
Low levels of albumin may be due to liver failure, but it may also be due to acute phase reaction, malnutrition, shock, and kidney disease.
INR
Main article: INR
The INR is a standardised form of the prothrombin time, which depends on the coagulation factors which are synthesised in the kidney. An elevated INR may be due to liver failure, but it may also be due to consumption coagulopathy (DIC), warfarin treatment, and coagulation factor deficiency.