Standard liver tests for assessing liver damage include alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP). Bilirubin may be used to estimate the excretory function of the liver and coagulation tests and albumin can be used to evaluate the metabolic activity of the liver.
Total bilirubin Measurement of total
bilirubin includes both unconjugated (indirect) and conjugated (direct) bilirubin. Unconjugated bilirubin is a breakdown product of
heme (a part of
hemoglobin in red blood cells). The liver is responsible for clearing the blood of unconjugated bilirubin, by 'conjugating' it (modified to make it water-soluble) through an enzyme named
UDP-glucuronyl-transferase. When the total bilirubin level exceeds 17 μmol/L, it indicates liver disease. When total bilirubin levels exceed 40 μmol/L, bilirubin deposition at the sclera, skin, and mucous membranes will give these areas a yellow colour, thus it is called
jaundice. The increase in predominantly unconjugated bilirubin is due to overproduction, reduced hepatic uptake of the unconjugated bilirubin and reduced conjugation of bilirubin. Overproduction can be due to the reabsorption of a
haematoma and ineffective
erythropoiesis leading to increased red blood cell destruction.
Gilbert's syndrome and
Crigler–Najjar syndrome have defects in the
UDP-glucuronyl-transferase enzyme, affecting bilirubin conjugation.
Alanine transaminase (ALT) Apart from being found in high concentrations in the liver, ALT is found in the kidneys, heart, and muscles. It catalyses the
transamination reaction, and only exists in a cytoplasmic form. Any kind of liver injury can cause a rise in ALT. A rise of up to 300 IU/L is not specific to the liver, but can be due to the damage of other organs such as the kidneys or muscles. When ALT rises to more than 500 IU/L, causes are usually from the liver. It can be due to hepatitis, ischemic liver injury, and toxins that causes liver damage. The ALT levels in
hepatitis C rises more than in hepatitis A and B. Persistent ALT elevation more than 6 months is known as
chronic hepatitis.
Alcoholic liver disease,
non-alcoholic fatty liver disease (NAFLD), fat accumulation in liver during childhood obesity,
steatohepatitis (inflammation of fatty liver disease) are associated with a rise in ALT. Rise in ALT is also associated with reduced insulin response, reduced glucose tolerance, and increased free
fatty acids and
triglycerides. Bright liver syndrome (bright liver on ultrasound suggestive of fatty liver) with raised ALT is suggestive of
metabolic syndrome. This wide range of AST containing organs makes it a relatively less specific indicator of liver damage compared to ALT. An increase of mitochondrial AST in bloods is highly suggestive of tissue
necrosis in
myocardial infarction and chronic liver disease. More than 80% of the liver AST activity are contributed by mitochondrial form of the isoenzymes, while the circulating AST in blood are contributed by cytoplasmic form of AST. AST is especially markedly raised in those with
liver cirrhosis. It can also be found on the mucosal epithelium of the small intestine,
proximal convoluted tubule of the kidneys, bone, liver, and placenta. It plays an important role in lipid transposition in small intestines and calcification of bones. 50% of all the serum ALP activities in blood are contributed by bone. Acute viral hepatitis usually has normal or increased ALP. For example, hepatitis A has increased ALP due to
cholestasis (impaired bile formation or bile flow obstruction) and would have the feature of prolonged itching. Other causes include: infiltrative liver diseases, granulomatous liver disease, abscess,
amyloidosis of the liver and
peripheral arterial disease. Mild elevation of ALP can be seen in liver cirrhosis, hepatitis, and
congestive cardiac failure. Transient
hyperphosphataemia is a benign condition in
infants, and can reach normal level in 4 months. In contrast, low levels of ALP is found in
hypothyroidism,
pernicious anemia,
zinc deficiency, and
hypophosphatasia. Levels in the third trimester can be as much as 2-fold greater than in non-pregnant women. As a result, ALP is not a reliable marker of hepatic function in pregnant women. == Other tests ==