Evaluating the results of hepatic enzyme testing is an important, albeit sometimes confusing, part of primary care practice. Here are a few pointers on assessing the results of AST and ALT measurement.
The most commonly performed tests of liver function are hepatic enzymes, which are protein molecules acting as catalysts and regulate metabolism within cells. When obtaining a measure of hepatic enzymes such as aspartate aminotransferase (AST) or alanine aminotransferase (ALT), you are asking, "Is hepatic cell injury present? How severe is this injury?"
AST is found in large quantities in hepatocyte. Small amounts are typically found in circulation due to hepatic growth and repair. AST has a circulatory half-life of approximately 12-24 hours. Thus, levels rise in response to hepatic damage and clear quickly once damage ceases. This enzyme is also found in skeletal muscle, myocardium, brain, and kidney in smaller amounts, so that damage to these areas may also cause an AST rise. AST can also rise in response to hepatocyte injury, as may occur with alcohol abuse, the therapeutic use of HMG CoA reductase inhibitors (lipid-lowering drugs with a "statin" suffix such as lovastatin) or acetaminophen overdose. One way to remember these causes is that AST can rise in response to the use of :
AST elevation is generally found in only about 10% of problem drinkers. However, if AST is elevated with normal ALT and mild macrocytosis (MCV>100, a combination seen in about 30-60% of men who drink 5 or more drinks per day and in women at a threshold of 3 or more drinks per day), long-standing alcohol abuse is the most likely cause.
ALT is more specific to the liver with limited concentration in other organs. This enzyme has a longer half-life (37-57 hours) than AST. As a result, elevation persists longer after hepatic damage has ceased. ALTís greatest elevation occurs in hepatitis caused by infection or inflammation. This enzyme is unlikely to rise significantly in the presence of alcohol abuse. In addition, ALT elevation may be seen in the use of certain therapeutic agents. One way to remember these causes is that ALT can rise in response to the use of:
Elevated ALT has been observed in less than 2% of patients on troglitazone, with return to normal found in nearly all after discontinuation of the drug.
|Troglitazone (Rezulin) use as well
as with certain other Therapeutic agents
When evaluating the person with suspected hepatic dysfunction, the NP must note both the degree of AST or ALT elevation as well as the AST/ALT ratio. Here are some examples:
AST rises higher than ALT in response to alcohol-related hepatic injury, usually at a ratio of 2:1 to 8:1, with the AST at 1-5 times norm. If the AST:ALT ratio > 8:1, consider other forms of hepatic damage. Take, for example, a 38-year-old man with a 10 year history of increasingly heavy alcohol use, AST= 83u/l (0- 31u/l), ALT=40u/l (0- 31u/l). In general, alcohol and drug-related AST elevations are usually less than 5 times the norm, or under 150u/l.
ALT rises higher than AST. This is found in infectious hepatitis A, B, C, D, E or G, as well as select additional therapeutic agents. When seen in infectious hepatitis, ALT elevations are usually marked and may be 10-30 times above the norm. Take for example, a 22-year-old woman who recently returned from a volunteer trip to a developing nation and contracted hepatitis A, AST= 678u/l (0- 3u/l), ALT= 828u/l (0-31u/l). In comparison, a drug-induced ALT elevation is more likely to be 1-3 times the norm or below 100u/l.
For more information on this complicated subject, you will find Laboratory Data Interpretation: A Case Study Approach helpful.
Nicoll, D., McPhee, S., Chou, T, Detmer, W. (1997) Pocket Guide to Diagnostic Tests. Stamford, CT: Appleton and Lange.
Liver, biliary tract and pancreas. In Tierney, L, McPhee, S. Papadakis (1999) Current Medical Diagnosis and Treatment. Stamford, CT: Appleton and Lange, pp. 638-677.