About Authors: Sharath Babu
M.Pharm, Mallareddy Institute of Pharmacy
Liver Enzymes
Four separate liver enzymes are included on most routine laboratory tests. They are-aspartate aminotransferase (AST or SGOT) and alanine aminotransferase (ALT or SGPT), which are known together as transaminases; and alkaline phosphatase (AP) and gamma-glutamyl transferase (GGT), which are known together as cholestatic liver enzymes. Elevations of these enzymes can indicate the presence of liver disease.
Reference ID: PHARMATUTOR-ART-1089
AST and ALT (Transaminases)
AST and ALT are jointly known as transaminases. They are associated with inflammation and/or injury to liver cells, a condition known as hepatocellular liver injury. Damage to the liver typically results in a leak of AST and ALT into the bloodstream.
Because AST is found in many other organs besides the liver, including the kidneys, the muscles, and the heart, having a high level of AST does not always (but often does) indicate that there is a liver problem. For example, even vigorous exercise may elevate AST levels in the body. On the other hand, because ALT is found primarily in the liver, high levels of ALT almost always indicate that there’s a problem with the liver. (Conversely, a normal ALT level does not necessarily mean that the liver is definitely normal- but, more about this later.)
Despite what one might expect, high levels of transaminases in the blood don’t always reveal just how badly the liver is inflamed or damaged. This is an extremely important point to keep in mind. The normal ranges for AST and ALT are around 0 to 40 IU/L and 0 to 45 IU/L respectively. (IU/L stands for international units per liter and is the most commonly accepted way to measure these particular enzymes.) But someone who has an ALT level of 50 IU/L is not necessarily in better condition than someone with an ALT level of 250 IU/L! This is because these blood tests measure inflammation and damage to the liver at an isolated point in time. For instance, if the liver is inflamed on the day that blood was drawn—let’s say if a patient consumes an alcoholic drink a few hours prior to blood being drawn—the levels of the transaminases may be much higher than if the alcohol had not been consumed. Following the same reasoning, if the liver was damaged years before—by excessive alcohol use—the results of a blood test done today may be normal, but a damaged liver may still be present.
To confuse issues even further, there are many other factors besides liver injury that could affect the levels of AST and ALT. For example, males have higher transaminase levels than females. And, African-American men have higher AST levels compared with Caucasian men. Even the time of day that a blood sample is drawn may influence the level of transaminase elevation. People appear to have higher transaminase levels in the morning and afternoon than in the evening. Food intake does not appear to have a significant effect on transaminase levels. Thus, levels do not significantly differ in the fasting and non-fasting state. Finally, transaminase levels may vary from day-to-day.
The ratio of the ALT and AST may also provide useful information regarding the extent and cause of liver disease. Most liver diseases are characterized by greater ALT elevations than AST elevations. Two exceptions to this rule exist. Both cirrhosis and/or alcohol abuse are associated with higher AST levels than ALT levels, often in a ratio of approximately 2:1.
Elevations of the transaminases occur due to so many causes that they give the doctor only a vague clue of the diagnosis. Additional testing is required in order to determine more precisely what is wrong with the liver. Some possible causes of elevated transaminase levels include the following:
• Viral hepatitis
• A fatty liver
• Alcoholic liver disease
• Drug/medication-induced liver disease
• Autoimmune hepatitis
• Herbal toxicity
• Genetic liver diseases
• Liver tumors
• Heart failure
- Strenuous exercise
GGT and AP (Cholestatic Liver Enzymes)
High levels of GGT and AP hint at a possible blockage of the bile ducts, or of possible injury to, or inflammation of, the bile ducts. This type of problem is characterized by an impairment, or failure, of bile flow, which is known as cholestasis. This type of liver injury is known as cholestatic liver injury, and this type of liver disease is known as cholestatic liver disease. (Primary biliary cirrhosis, discussed in Chapter 15, is an example of a cholestatic liver disease.) Intrahepatic cholestasis refers to bile duct blockage or injury within the liver. Intrahepatic cholestasis may occur in people with primary biliary cirrhosis or liver cancer (see Chapter 19), for example. Extrahepatic cholestasis refers to bile duct blockage or injury occurring outside the liver. Extra¬hepatic cholestasis may occur in people with gallstones.
When a blockage or inflammation of the bile ducts occurs, the GGT and AP can overflow like a backed up sewer and seep out of the liver and into the bloodstream. These enzymes typically become markedly elevated—approximately ten times the upper limit of normal.
GGT is found predominantly in the liver. AP is mainly found in the bones and the liver but can also be found in many other organs, such as the intestines, kidneys, and placenta. Therefore, elevated levels of AP will indicate that something is wrong with the liver only if the amount of GGT is raised as well. Keep in mind that, GGT can be elevated without AP being elevated, as GGT is a sensitive marker of alcohol ingestion and certain hepatotoxic (liver toxic) drugs. It should be noted that for unclear reasons, people who smoke cigarettes appear to have higher AP and GGT than nonsmokers. Also, levels of AP and GGT are most accurate after a twelve-hour fast. You are beginning to get an inkling of the complexities that arise when evaluating abnormal LFTs!
Normal levels of AP range from 35 to 115 IU/L and normal levels of GGT range from 3 to 60 IU/L.
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