Liver Function Tests

Liver Function Tests

Liver function tests are groups of blood tests that provide information about the state of the liver. These tests include total bilirubin (conjugated and unconjugated), aspartate transaminase (AST), alanine transaminase (ALT), gamma-glutamyl transferase (GGT), alkaline phosphatase (ALP), albumin, prothrombin time (PT/INR), and activated Partial Thromboplastin Time (aPTT).

These blood tests assess various aspects of the integrity of the liver. For example:

1. synthetic capacity or functionality
• Albumin: it is synthesized exclusively by the liver. It has a half-life of 21 days. Normal range is 35-50g/L. Albumin is the major constituent of total protein (the remaining are primarily globulins). An alternative to albumin measurement is prealbumin, which is better at detecting acute changes (prealbumin half-life is about 2 days).

  Causes of reduced Albumin are:

  • Liver cirrhosis
  • Nephrotic syndrome
  • Malnutrition
• Prothrombin time (10-14sec) measures how long it takes for blood to clot
2. integrity of the hepatocytes e.g., aspartate transaminase (AST), alanine transaminase (ALT)
3. integrity of the biliary ducts/channel e.g., gamma-glutamyl transferase (GGT) and alkaline phosphatase (ALP)
4. detoxification capacity e.g., bilirubin

Reference range: 7-56 IU/L

Alanine transaminase (ALT) catalyses the transamination reaction and only exists in a cytoplasmic form. It is found in high concentrations in the hepatocytes and also in the kidneys, heart, and muscles. A rise of up to 300 IU/L is not specific to hepatocytes but may be due to damage to other organs such as the kidneys or muscles.

Causes of elevated ALT include:

• ALT rise of up to 500 IU/L is usually of liver origin and may be due to
  1. Viral hepatitis e.g., hepatitis A, B, or C
  2. Hepatitis
  3. Ischaemic liver injury
  4. Toxic damage to the liver
  5. Alcoholic liver disease
  6. Non-alcoholic fatty liver disease (NAFLD)
  7. Fat accumulation in the liver during childhood obesity
  8. Steatohepatitis (inflammation of fatty liver disease)
  9. Glucose intolerance
  10. Elevated free fatty acids and triglycerides
  11. Metabolic syndrome
  12. In pregnancy (during the second trimester), and pregnancy-related conditions such as hyperemesis gravidarum, pre-eclampsia, haemolysis elevated liver enzymes and low platelets (HELLP syndrome). ALT levels are expected to reduce by greater than 50% in three days after child delivery.

Reference range: 0-35 IU/L

Aspartate transaminase (AST) exists in two isoenzymes, namely mitochondrial and cytoplasmic forms. It is found in the highest concentration in hepatocytes, followed by the heart, muscle, kidney, brain, pancreas, and lungs. As a result, AST is a less specific indicator of hepatocyte damage compared to ALT. If the rise in AST is less than two times the upper limit of normal AST, then no further workup needs to be performed.

Causes of elevated AST include:

• Chronic liver disease
• Liver cirrhosis
• Myocardial infarction
• In certain pregnancy conditions such as hyperemesis gravidarum, pre-eclampsia, and HELLP syndrome

The AST/ALT ratio increases in liver functional impairment.

Causes of elevated AST/ALT ratio:

1. In alcoholic liver disease: > 1.45
2. Post necrotic liver cirrhosis: > 1.33
3. Post viral hepatitis cirrhosis: > 1.17
4. Alcoholic hepatitis: > 2.0
5. Non-alcoholic hepatitis: > 0.9
6. Wilson disease or hyperthyroidism: > 4.5

Reference range: 41 to 133 IU/L

Alkaline phosphatase (ALP) is an enzyme in the cells lining the hepatic biliary ducts. It can also be found in the proximal convoluted tubule of the kidneys, mucosal epithelium of the small intestine, liver, placenta, and bone. ALP plays an important role in lipid transposition in the small intestines and calcification of bones. About 50% of all the serum ALP activities in blood are contributed by bone.

Causes of elevated ALP are:

• Acute viral hepatitis due to cholestasis (impaired bile formation or bile flow obstruction)
• Liver cirrhosis
• Infiltrative liver diseases
• Granulomatous liver disease
• Liver abscess
• Hepatic amyloidosis
• Peripheral arterial disease
• Congestive cardiac failure
• Transient hyperphosphataemia
• Pregnancy (third trimester) due to increased synthesis from the placenta
• In pregnancy conditions such as hyperemesis gravidarum, pre-eclampsia, and HELLP syndrome. GGT is particularly important in helping eliminate the bone as the source of elevated ALP since it is not elevated if the source is the bone.

Reference range: 9 to 85 IU/L

Gamma glutamyltransferase (GGT) is a microsomal enzyme found in hepatocytes, biliary epithelial cells, pancreas, intestine, and renal tubules. It helps in glutathione metabolism by transporting peptides across the cell membrane.

Causes of elevated GGT include:

• Acute viral hepatitis
• Non-alcoholic liver disease
• Alcoholism
• Diabetes mellitus
• Obesity
• Hyperthyroidism
• Acute myocardial infarction
• Anorexia nervosa
• Guillain–Barré syndrome
• Myotonic dystrophy
• In pregnancy conditions such as hyperemesis gravidarum, pre-eclampsia, and HELLP syndrome

Reference ranges:

• Total Bilirubin: 2.0-21 μmol/l
• Unconjugated Bilirubin: < 12 μmol/l
• Conjugated Bilirubin: < 8 μmol/l

The assay of total bilirubin includes unconjugated (indirect) and conjugated (direct) bilirubin. Unconjugated bilirubin is a breakdown product of heme (a component of red blood cell haemoglobin). The liver is responsible for clearing the blood of bilirubin (unconjugated) by 'conjugating' it to make it water-soluble through the enzyme UDP-glucuronyl-transferase. A total bilirubin level greater than 17 μmol/l indicates liver disease. When total bilirubin levels exceed 40 μmol/l, bilirubin is deposited in the mucous membranes, skin, and sclera, and these areas become yellowish in color, and therefore called jaundice.

Causes of predominantly unconjugated hyperbilirubinemia are:

1. Overproduction (from reabsorption of hematoma and dyserythropoiesis). Haemolytic jaundice is the commonest cause of pathological jaundice. Babies with Rh haemolytic disease, ABO incompatibility with the mother, Glucose-6-phosphate dehydrogenase (G-6-PD) deficiency, and minor blood group incompatibility are at increased risk of getting haemolytic jaundice.
2. Reduced hepatic uptake of unconjugated bilirubin
3. Reduced conjugation of bilirubin (Gilbert's syndrome and Crigler–Najjar syndrome have defects in the UDP-glucuronyl-transferase enzyme, affecting bilirubin conjugation)

Causes of predominantly conjugated hyperbilirubinemia are:

1. Hepatocyte injury e.g., viral hepatitis, parenchymal liver disease
2. Extra-hepatic obstruction
3. CBD obstruction due to malignant causes
4. Dubin–Johnson syndrome, a mutation in multiple drug-resistance protein 2 (MRP2)

1. Evaluation and management in liver dysfunction.
2. To detect the presence of liver disease in conditions such as hypertriglyceridemia, diabetes mellitus, systemic hypertension, etc.
3. To differentiate types of liver diseases.
4. To ascertain the extent of liver damage in infections such as hepatitis B and C.
5. To monitor response to treatment.
6. To evaluate the effect of some medications on the liver e.g., as anti-hypertensives, anticonvulsants, etc.

These vary depending on the age, sex, ethnic group, race, analytical method, and units of measurement. Individual results can only be reliably interpreted using the reference range provided by the laboratory that performed the test.