Last Updated on May 28, 2020
Liver function tests are blood tests that are used to diagnose and monitor liver disease.
An individual liver function test by itself has neither high sensitivity nor specificity. However, when interpreted together along with the clinical symptoms of the patient, they provide useful information about the condition of the liver. In addition, they may also indicate other health conditions including kidney disease, malnutrition, bone disease, etc.
Functions of Liver
The liver is a vital organ of the body which performs many important functions. These include:
- Detoxification of blood
- Production of albumin, clotting factors, and many other important proteins
- Metabolization of drugs and nutrients
- Synthesis and excretion of bile which is essential for digestion and absorption of fats and vitamins.
- Processing of waste products of hemoglobin and other cells
- Storing of vitamins, fat, cholesterol, and bile
- Production of glucose (gluconeogenesis) which is released during starvation
- Break down and synthesis of cholesterol
Why Are Liver Function Tests Done?
Liver function tests are carried out for the following reasons:
- To screen and detect liver diseases.
- To distinguish between different liver disorders.
- To monitor the progression of liver disease.
- To estimate the severity of the liver disease, in case of cirrhosis.
- To determine the effectiveness of treatment.
- To monitor and detect side effects of medications. This includes medicines given for diseases not involving the liver.
Bilirubin (Total, Direct and Indirect)
It measures the amount of
-
Total bilirubin
-
Unconjugated (indirect) bilirubin
-
Conjugated (direct) bilirubin
Reference range in adults
- Total bilirubin: 0.1–1.0 mg/dL
- Unconjugated bilirubin: 0.2-0.7 mg/dL
- Conjugated bilirubin: 0.1–0.4 mg/dL
Bilirubin is produced during the normal breakdown of red blood cells (RBCs). Breakdown of heme which is a part of hemoglobin present in RBCs produces unconjugated bilirubin as a waste product. In the liver, bilirubin is conjugated to form conjugated bilirubin which makes it water-soluble.
If the liver is unable to conjugate bilirubin or can’t excrete conjugated bilirubin, the levels of bilirubin will rise. This excess bilirubin gets deposited in sclera, skin, and mucous membranes imparting a yellowish discoloration to these areas. This is called jaundice.
Causes of Increase in Unconjugated bilirubin
Excessive production of bilirubin
- Hemolytic anemias
- Ineffective erythropoiesis (Pernicious anemia, Thalassemia)
- Resorption of hematomas
Defect in hepatic conjugation
- Gilbert syndrome
- Crigler–Najjar syndrome
- Physiological jaundice of the newborn
- Breast milk jaundice
- Acute or chronic liver disease
- Drug-induced hepatitis
Causes of Increase in Conjugated bilirubin
- Acute or chronic liver disease
- Viral hepatitis
- Alcoholic liver disease
- NASH (nonalcoholic steatohepatitis)
- Drug toxicity (eg, acetaminophen)
- Hemochromatosis
- Wilson disease
- Autoimmune hepatitis
- Alpha-1 antitrypsin deficiency
- Dubin-Johnson syndrome
- Rotor syndrome
- Diseases that prevent the flow of bile into the intestine
- Primary biliary cirrhosis
- Graft versus host disease
- Choledocholithiasis (stone in the bile duct)
- Sclerosing cholangitis
- Postsurgical strictures
- Developmental disorders of the bile ducts (eg, Caroli disease)
- Extrinsic compression of the bile duct
- Acute pancreatitis
- Cancer of bile duct or pancreas
Serum glutamic pyruvic transaminase (SGPT) or Alanine aminotransferase (ALT)
Serum glutamic oxaloacetic transaminase (SGOT) / Aspartate transaminase (AST)
Reference range
- ALT: 7-56 U/L
- AST: 5-40 U/L
The aminotransferases are the enzymes that catalyze chemical reactions in which an amino group from one amino acid is transferred from a donor molecule to a recipient molecule. They help to convert proteins into energy for the liver cells
ALT catalyzes the transfer of an amino group from alanine to a-ketoglutarate. This reversible transamination reaction results in the production of pyruvate and glutamate.
L-alanine + α-ketoglutarate ⇌ pyruvate + L-glutamate
AST catalyzes the conversion of aspartate and α-ketoglutarate to form glutamate and oxaloacetate.
Aspartate + α-ketoglutarate ⇌ oxaloacetate + glutamate
ALT is found primarily in the liver. It is also present in low quantities in the kidney. In case of liver damage, ALT is released into the blood and its levels increase.
AST is found mainly in the liver and heart. Besides it is also found in many other tissues including the muscle, red blood cells (RBCs), pancreas, kidney, and brain. Any damage to these organs or hemolysis of RBCs causes the release of the enzyme, resulting in increased levels of AST in the blood.
ALT is usually measured along with AST as part of the liver function tests panel to detect liver damage.
Causes of increase in ALT and AST
- Liver damage (acute viral hepatitis, toxins/drugs including acetaminophen overdose, acute fulminant hepatitis)
- Chronic liver disease
- Alcohol abuse
- Liver tumors
- Cirrhosis
- Fatty change of liver
- Cholestasis
- Heart damage (heart attack or myocardial infarction, heart failure)
- Kidney damage
- Muscle injury
- Hemolysis
- Heatstroke (level dependent on the extent of tissue damage)
- Infectious mononucleosis
- Drugs (ie, statins, aspirin, barbiturates, HIV medication, herbs, etc)
ALT is more specific for liver damage as it is found mainly in the liver and has a longer half-life. AST, on the other hand, is found in many other organs.
A normal ALT and raised AST usually indicate a normal liver but the involvement of other organs (heart disease, muscle injury or hemolysis).
Any kind of damage to muscle tissue including strenuous exercise or even muscle injections can increase AST levels
Liver diseases in which AST is higher than ALT include alcohol-induced liver damage, cirrhosis, and liver tumors.
In acute hepatitis, AST levels remain high for about 1–2 months. Also, it takes about 3–6 months for the levels to return to normal. In chronic hepatitis, AST levels are usually not as high, usually less than 4 times the highest normal level.
AST: ALT ratio (De Ritis ratio) has practical importance.
In alcoholic liver disease, AST: ALT ratio is greater than 2.
The levels of these liver enzymes do not correlate well with the extent and severity of liver disease and can’t be used to determine the prognosis. For example, patients suffering from acute viral hepatitis A may have extremely high levels of AST and ALT (sometimes the levels may reach thousands of units/liter), but most such patients will recover fully without any residual liver disease. On the other hand, in patients of chronic hepatitis C, levels of AST and ALT levels are only mildly elevated although they may have significant liver damage or even cirrhosis of the liver.
Liver Protein Tests
This test includes the measurement of the following parameters
- Total protein
- Albumin
- Globulin
- Albumin: globulin (A: G ratio)
Total protein
Reference range
6.0–8.0 mg/dL
It measures the total amount of protein present in the blood. The two main proteins found in the blood are albumin and globulins.
Causes of low total protein
- Liver disorder
- Kidney disorder
- Celiac disease
- Poor nutrition
Causes of high total protein
- Chronic infection or inflammation
- Bone marrow disorder including cancers
- Dehydration (factitious high value)
Albumin
Reference range
3.5–5.0 mg/dL
Albumin is synthesized exclusively by the liver.
It performs the following functions in the body:
- Provides nourishment to the body tissues.
- Helps to transport hormones, vitamins, and other substances throughout the body.
- Prevents leakage of fluid from the blood vessels.
It is a useful indicator of liver function. Since the half-life of albumin in serum is long-about 20 days, its level is not a reliable indicator of liver protein synthesis in acute liver disease. Reduced levels are significant in chronic liver disease of more than three weeks duration
Its synthesis is affected not only in chronic liver disease but also by nutritional status, hormonal balance, and osmotic pressure.
Causes of low albumin
- Chronic liver disease of more than three weeks duration
- Poor nutrition
- Kidney disease (eg. Nephrotic syndrome)
Causes of high albumin
- Infection and inflammation
- Dehydration (factitious high value)
Measurement of prealbumin can be used instead of albumin to diagnose acute liver conditions. This is because the half-life of prealbumin is about 2 days in comparison with albumin which has a half-life of about 20 days.
Globulin
Reference range
2.5–3.5 mg/dL
Globulin is made by the liver as well as the immune system.
It plays an important role in liver function, blood clotting, and fighting infection. There are four main types of globulins. These include alpha 1, alpha 2, beta, and gamma globulins.
Causes of low globulin levels
- Liver disease
- Kidney disease
- Poor nutrition
Causes of high globulin levels
- Infections and inflammations
- Allergies
- Autoimmune disorders such as lupus and rheumatoid arthritis
- Certain types of cancer eg : multiple myeloma, Hodgkin’s disease or malignant lymphoma. In multiple myeloma levels of gamma globulins are markedly increased.
Albumin: globulin (A: G ratio)
Reference range
0.8-2.0
It is the ratio of albumin present in serum in comparison with the amount of globulin. It should be interpreted in the context of total protein concentration. High total protein with a normal A: G ratio suggests dehydration, while the same protein with a low A: G ratio would indicate hyperglobulinemia.
Causes of low A: G ratio
- Cirrhosis
- Kidney disease
- Autoimmune disorder
- Tumor involving the bone marrow ( multiple myeloma)
Causes of high A: G ratio
- Liver disease
- Kidney disease
- Low thyroid activity
- Leukemia
Coagulation Panel (Prothrombin Time or PT, and International Normalized Ratio or INR)
Certain proteins ( eg. prothrombin) synthesized in the liver play an important role in blood clotting. Thus they prevent bleeding and bruising.
A prothrombin time test and INR test measures the time taken for blood to clot.
Increased prothrombin time can be a sign of liver damage.
Alkaline Phosphatase (ALP)
Reference range
44-147 U/L
It is present in all tissues of the body but is mainly present in the liver, bones, kidneys, digestive system and placenta.
ALP levels vary with age or other conditions. Children and teenagers have high levels of ALP because their bones are growing. Higher levels of ALP are also normally seen in pregnancy.
Causes of high levels of ALP
- Biliary obstruction
- Choledocholithiasis (stone in the bile duct)
- Bile cancers
- Bone tumors
- Osteomalacia
- Acute cholecystitis — inflammation of the gallbladder
- Liver cancer
- Benign tumors of the liver
- Cirrhosis
- Viral hepatitis
- Alcoholism
- Infiltrative liver diseases, granulomatous liver disease, abscess, amyloidosis of the liver, hepatotoxic drugs
Causes of low levels of ALP
Hypothyroidism
Malnutrition, deficiencies in vitamin D, calcium, protein, magnesium, and zinc
Hypophosphatasia
Gamma-Glutamyl Transferase (GGT)
Reference range
9–48 U/L
It is an enzyme that is mainly concentrated in the liver. Besides, it is also present in the gallbladder, spleen, pancreas, and kidneys.
Its main function in the body is to transport molecules. It plays an important role in helping the liver to metabolize drugs and other toxins.
It is usually the first liver enzyme to rise when there is any injury or obstruction to the bile duct. This makes it the most sensitive liver enzyme test for detecting diseases of the bile duct.
However, it is not very specific. Also, it can’t be used to differentiate between the different causes of liver damage. In general, the higher the level, the greater the damage to the liver.
It is not recommended to use this test in isolation.
Its significance lies in its use along with other liver function tests It can be used to determine the cause of a high alkaline phosphatase (ALP) In liver diseases, levels of both GGT and ALP are increased, but in diseases affecting the bones, only ALP is increased. Therefore, GGT can be used to determine if the high ALP is due to liver or bone disease.
GGT levels are temporarily increased by the consumption of even small amounts of alcohol. Higher levels of GGT are found more commonly in chronic heavy drinkers. GGT test can be used to evaluate both acute and chronic alcohol abuse.
Causes of increased GGT
- Alcohol abuse
- Bile duct diseases
- Chronic viral hepatitis
- Liver tumor
- Cirrhosis
- Heart failure
- Atherosclerosis
- Pancreatitis
- Diabetes
- Overuse of certain drugs and toxins
- Fatty liver disease
Conclusion
Any individual liver function test is not very significant for screening liver diseases. Many serious or end-stage liver diseases may be associated with normal or mildly raised levels of different liver function tests. In many cases, abnormal levels may be found in completely asymptomatic healthy individuals.
Complete liver function tests panel, when interpreted in conjunction with signs and symptoms of the patient, provide very useful information regarding the patient’s illness.
It also helps to guide the treating doctor about further investigations required to be performed. These may include viral hepatitis markers (eg, HBsAg, HCV, HAV), serum electrophoresis, cardiac disease markers, ultrasonography, computed tomography , etc.