Liver Function Tests

Diagnosing Liver Disease

Liver Enzyme Tests

The most commonly used markers of hepatocyte injury are aspartate aminotransferase (AST), formerly serum glutamic-oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT), formerly serum glutamate-pyruvate transaminase [SGPT]). While ALT is cytosolic, AST has both cytosolic and mitochondrial forms.

Hepatocyte necrosis in acute hepatitis, toxic injury or ischemic injury results in the leakage of enzymes into the circulation. However, in chronic liver diseases such as hepatitis C and cirrhosis, the serum ALT level correlates only moderately well with liver inflammation. In hepatitis C, liver cell death occurs by apoptosis (programmed cell death) as well as by necrosis. Hepatocytes dying by apoptosis presumably synthesize less AST and ALT as they wither away. This probably explains why at least one third of patients infected with hepatitis C virus have persistently normal serum ALT levels despite the presence of inflammation on liver biopsy.

Patients with cirrhosis often have normal or only slightly elevated serum AST and ALT levels. Thus, AST and ALT lack some sensitivity in detecting chronic liver injury. Of course, AST and ALT levels tend to be higher in cirrhotic patients with continuing inflammation or necrosis than in those without continuing liver injury.

Slight  AST or ALT elevations (within 1.5 times the upper limits of normal) do not necessarily indicate liver disease. Part of this ambiguity has to do with the fact that unlike the values in many other biochemical tests, serum AST and ALT levels do not follow a normal bell-shaped distribution in the population.  Instead, AST and ALT values have a skewed distribution characterized by a long “tail” at the high end of the scale.

AST and ALT values are higher in obese patients, probably because these persons commonly have fatty livers.  ALT levels have been noted to decline with weight loss.   Rare individuals have chronically elevated AST levels because of a defect in clearance of the enzyme from the circulation.   Mild elevations of ALT or AST in asymptomatic patients can be evaluated efficiently by considering alcohol abuse, hepatitis B, hepatitis C and several other possible diagnoses.

Various liver diseases are associated with typical ranges of AST and ALT levels.   ALT levels often rise to several thousand units per liter in patients with acute viral hepatitis. The highest ALT levels–often more than 10,000 U per L–are usually found in patients with acute toxic injury subsequent to, for example, acetaminophen overdose or acute ischemic insult to the liver. AST and ALT levels usually fall rapidly after an acute insult.