ALT: Does it Actually Measure Liver Function?

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You have likely heard your doctor discuss “liver function tests” and you may have wondered what that meant.  Actually, the term “liver function test” is a bit of a misnomer for the tests most physicians are commonly referring. These include the liver enzymes AST, ALT, and alkaline phosphatase plus bilirubin.  The reason that “liver function” is a misnomer is because these tests don’t really assess the function of the liver.

Of these four tests, ALT has taken on special significance as a marker of liver injury.  What is it and what does it tell us? (ALF)

ALT is an abbreviation for the technical name, alanine aminotransferase (WebMD).  It was formerly called SGPT (or serum glutamate pyruvate transaminase) (Medicinenet), and some labs still report it using the obsolete name. ALT is an enzyme, or protein, found almost exclusively in the liver (eMedicine).  It floats in the liquid cytoplasm of the liver cell in relatively high concentrations.  When there is damage to the liver membrane there is leakage of the liquid cytoplasm into the bloodstream, and hence a rise in the blood ALT level. The amount of ALT activity in the blood correlates very closely with the amount of liver damage (or necrosis), so it becomes a useful indicator of the death of liver cells.  The AST (aspartate aminotransferase), previously referred to as SGOT, is a similar enzyme found in the liver cytoplasm, but is also found in several other organs including heart, muscle and red blood cells.

The two tests, when used together, provide much useful information about the cause and severity of liver disease.

The ALT enzyme, after release from the liver, circulates in the bloodstream over twice as long (half-life of 47 hours) as AST (half-life 17 hours).  So most cases of liver injury, whether acute hepatitis, chronic hepatitis or drug injury, are typically associated with an ALT level higher than AST.

In two very specific circumstances, the AST may be higher than the ALT: alcoholic liver disease and also when cirrhosis develops in chronic hepatitis C. For example, in acute alcoholic hepatitis the AST is typically two-fold greater than the ALT, but neither should be more than 10-fold above normal. In another example, chronic hepatitis C without cirrhosis is associated with an ALT level higher than the AST, but when cirrhosis develops, they flip and the AST becomes higher than the ALT.

The ALT is also used alone as a screening test for the presence of liver injury, but is less helpful in identifying the cause. The normal laboratory cut-off for the upper limit of normal for ALT is typically reported in most reference laboratories as 35 or 40 IU/mL.  However, recent studies suggest that these normal levels probably are overestimates.  The true upper normal cut-off for men should be 30 IU/mL, and for women the cut-off should be 19 IU/mL.  This is likely due to the fact that “normal” ranges for the reference laboratory often include subjects who are obese and may have undiagnosed fatty liver disease which can be associated with an elevated ALT. When these subjects are excluded, the true normal range is realized.

It is for this reason, that a laboratory "normal" ALT should not exclude the possibility of liver disease in someone who has symptoms and risk factors for liver disease. Interestingly, many subjects with hepatitis C and moderately elevated ALT levels have these levels decline to very low levels after eradication of the virus - sometimes into single digits.

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