Liver Function Tests (LFTs)

The liver carries out numerous synthetic, excretion and detoxification functions, however only a minority of these can be measured by levels of products in the blood. Liver function tests (LFTs) measure the concentrations of various different proteins and enzymes in the blood that are either produced by liver cells or released when liver cells are damaged. Liver function tests are very common investigations carried out in people with suspected liver disease. Specific patterns of results can tell your doctor the likely type of liver disease so they can decide whether any further tests are required. Liver function tests can also help tell how severely the liver is damaged and help monitor your response to drugs and other treatments.

The procedure

The term “liver function tests” is actually a misnomer as several of the tests do not measure total liver function at all. Levels of enzymes known as aminotransferases and alkaline phosphatase are used to detect damage to liver cells and obstruction by bile (a substance produced by liver cells to help digest fats) respectively. Thus, liver tests can be divided into measures of liver function, cell injury and biliary obstruction. No single test is able to provide an overall measure of liver function. Instead the group of values measured is interpreted collectively to determine the likelihood of liver disease, possible causes and the severity of disease. Laboratory tests of liver function can also be used to monitor the progress of disease and the response to treatments. LFTs are performed after a simple blood test. The requirements for preparation differ between laboratories. Some require the patient to have fasted overnight but often no specific preparations are required. Collection of samples for LFTs follows a simple, safe and quick procedure. After checking your name and identification, a physician or trained phlebotomist (person who takes blood samples) will place a tourniquet (a tight strap) around your arm to help them identify a suitable vein, usually in front of your elbow. You may have to pump your hand a number of times to increase the blood flow to this area. After disinfecting the site with an alcohol wipe, they will insert a needle into the vein to withdraw blood. Sometimes a special butterfly apparatus is used, especially if multiple blood samples are to be collected at once. Once blood has been drawn into the required number of tubes, the needle and tourniquet will be removed. Pressure is then applied to the area to stop bleeding. Usually the whole procedure is completed in a short space of time with minimal pain or discomfort for the patient. Blood tubes are sent to the appropriate laboratory where the following values are measured. Note that different laboratories may have different cut-off values for each test as they may use different methods.

• Total protein: Total protein should be between 63-80g/L and reflects the synthetic functions of the liver.
• Albumin: This protein is produced only by liver cells, thus its concentration reflects liver synthetic function. Albumin stays in the blood for a long period of time so changes in its level occur only in chronic (long-standing) liver disease. Normal values for albumin are between 35-50 g/L. Other conditions can produce low levels of albumin. Malnutrition may decrease albumin as not enough protein is absorbed into the body. Kidney damage can result in loss of albumin into the urine. Low levels of albumin cause peripheral oedema, which is swelling (typically of the ankles) due to low levels of salts and proteins in the blood.
• Bilirubin: Bilirubin is produced in the breakdown of red blood cells in the body. The liver is usually responsible for the detoxification of bilirubin and its excretion into bile. An increase in the total level of bilirubin produces the symptom known as jaundice. Jaundiced patients have yellow discolouration of their skin and the sclera (whites) of their eyes. Bilirubin is not only increased in liver disease but other conditions that cause an increased breakdown of red blood cells. Normal values for total plasma bilirubin are quoted as less than 20 umol/L.
• Alkaline Phosphatase (ALP): This enzyme is mainly implicated in the diagnosis of biliary obstruction and is normally found in small bile tracts in the liver. There are many different types of this enzyme found in the body in the liver, bone and placenta so elevated levels may be due to a problem outside the liver such as a malignancy (cancer). A normal ALP is between 35-50 g/L.
• Gamma Glutamyl Transpeptidase (GGT): GGT enzyme is found in certain liver cells and bile duct cells. It is also elevated in diseases that decrease or obstruct the flow of bile. Alcohol abuse, warfarin (a blood-thinner) and drugs used for epilepsy can increase GGT levels. GGT has been used to detect chronic alcohol abuse but it is increased in a range of conditions so it is not always correct. GGT should be less than 60U/L in a normal individual.
• Alanine Amino Transferase (ALT) & Aspartate Amino Transferase (AST): Both aminotransferase enzymes are good markers of damage to liver cells that occurs in disorders such as viral hepatitis. AST is found in the liver, cardiac muscle, skeletal muscle, kidneys, brain, pancreas, lungs, leukocytes (white blood cells) and erythrocytes (red blood cells) whilst ALT is found primarily in the liver. Both enzymes are normally present at low levels in the blood so if liver cells are damaged we would expect some of the enzymes to leak into the blood and increase levels. Virtually any injury to liver cells can raise aminotransferase levels. However, the level of enzymes does not necessarily reflect how severely the liver is damaged. Reference values for ALT are less than 36U/L and for AST are less than 42U/L.
• Ammonia: Ammonia is a by-product of protein metabolism and is produced by bacteria in the large intestine. The liver is responsible for the detoxification of ammonia by converting it to urea (a product found in urine). Sometimes ammonia levels will be measured in the blood to gain further information about liver function and the presence of encephalopathy (a condition where ammonia toxins impair brain function leading to confusion and tremors). However, ammonia blood levels correlate poorly with the above situations so measurements have their limitations. Reference values for ammonia vary widely between laboratories.

Results usually come back from the laboratory promptly (often the same day in hospital). Once the tests come back from the laboratory, any abnormalities and their meanings will be discussed with the patient.

Benefits and Risks

The benefits of liver function tests have already been alluded to. In summary these include:

1. Detection of liver disease
2. Determining the likely type of disease and possible causes
3. Determining the severity or stage of disease
4. Monitoring the response to treatment

Risks of the actual procedure are minimal. Some patients may experience bleeding or haematomas (large bruises) at the venepuncture site (where blood was taken). These are in fact more common in patients with severe liver disease as the liver is unable to produce sufficient clotting factors to stop bleeding. Fainting, dizziness and lightheadedness may also occur.

Limitations

Liver function tests have various limitations and are only a small part of overall patient evaluation. Doctors will interpret the results after considering the patient as a whole, including medical history and signs and symptoms at presentation. Like many other investigations, LFTs do not always produce reliable results. They may be normal in patients with serious liver disease and abnormal in patients without liver disease or other diseases that may interfere with results. Liver tests don’t usually tell the doctor the exact type of disease but give them clues of the likely type of disease so they can do more definitive tests and investigations. For example, results suggesting damage to liver cells may trigger the physician to do tests looking for viruses in the blood that cause hepatitis. In addition, several drugs and other medical conditions can interfere with results so they may not necessarily provide the needed information. Patients may need to have the tests repeated or have different investigations performed.

Results of the Tests

Discussed below are some common patterns of liver function tests and their interpretations that may be discussed with patients. It should be noted that liver function tests can have various different values even in the same condition. They often add only small amounts of information to the final diagnosis. Large elevations of AST or ALT occur in conditions with marked damage to liver cells including viral hepatitis or drug-induced injury. In alcoholic liver disease, AST is often much more elevated than ALT. To contrast, in viral hepatitis or non-alcoholic fatty liver disease ALT is often much higher than AST. Elevated levels of both ALP and GGT are highly suggestive of obstructive disease. However, these values often aren’t able to tell the site of obstruction. ALP can also come from form bone, placenta or prostate cancer. Increased levels of GGT alone, may suggest alcohol or other drug use. Elevated bilirubin without any other abnormal LFTs occurs in conditions that break down red blood cells and in Gilbert’s syndrome. Low levels of albumin occur in chronic conditions such as cirrhosis. Sometimes results may be a mixed picture of liver damage and bile obstruction that can occur in various liver diseases. Liver function tests are only a small part of the diagnostic workup. Following interpretation of results several special tests for other markers and liver imaging may be performed to gain further information about the aetiology of liver disease. If the cause of the symptoms can be determined, treatment may be started. This may include antiviral medications to treat viruses, advice and medications to help reduce alcohol consumption, medications to protect the liver and other drugs to treat some of the symptoms of liver disease.

References

1. Braunwald, Fauci, Kasper, Hauser, Longo, Jameson. Harrison’s Principles of Internal Medicine. 15th Edition. McGraw-Hill. 2001.
2. Longmore, Wilkinson, Rajagopalan. Oxford Handbook of Clinical Medicine. 6th Edition. Oxford University Press. 2004.