Liver Function Testing


Liver function tests are blood tests, used to assess the general state of the liver or biliary system. Few of these tests actually measure how well the liver or biliary system is functioning, but rather reflect the presence of damage or inflammation.

A major problem in relying on these biochemical tests is that they are indirect measurements from the blood, of what is happening in the liver. Their major use is to guide the physician along with the history and physical examination, in the diagnosis and management of a number of liver diseases.

Perhaps the most commonly used indicators of liver (hepatocellular) damage are the alanine aminotransferase (ALT) and aspartate aminotransferase (AST), formally referred to as the SGPT and SGOT. These are enzymes normally found in liver cells, that leak out of these cells and make their way to the blood when liver cells are injured. The ALT is felt to be a more specific indicator of liver inflammation as AST is also found in other organs such as the heart and skeletal muscle. In acute injury to the liver, as in viral hepatitis, the level of the ALT and AST may be used as a general measure of the degree of liver inflammation or damage. In chronic liver disease, this is not the case, for these enzymes may be entirely within the normal range (usually < 50 IU/1), even in the presence of cirrhosis (liver scarring).

The alkaline phosphatase is the most frequently used test to detect obstruction in the biliary system. Elevation of this enzyme may be found in a large number of disorders as common as gallstone disease, alcohol abuse, and drug-induced hepatitis, or in less common disorders such as primary biliary cirrhosis or biliary tumors. Although this enzyme is found both in the liver and bile, and leaks into the bloodstream in a manner similar to that described for the ALT and AST, alkaline phosphatase is also found in other organs such as bone, placenta, and intestine. For this reason, it is often useful to measure another enzyme not found in these organs, either the 5'-nucleotidase (5'-NT) or the gamma-glutamyl transpeptidase (GGTP), along with the alkalIne phosphatase when the origin of the elevated alkaline phosphatase (normal < 115 IU/1) is not clear. Abnormalities of the 5'-NT or GGTP would then suggest liver or biliary tract disease.

Billrubin is the main bile pigment in humans which, when elevated causes the yellow discoloration of the skin called jaundice. Billrubin is formed primarily from the breakdown of a substance called heme (found in red blood cells). It is taken up from the blood, processed, and then secreted into the bile by the liver. There is normally a small amount of billrubin in the blood in healthy individuals (< 1.2mg/dl). Conditions which cause increased formation of billrubin (such as destruction of red blood cells) or decrease its removal from the blood stream (as in liver dysfunction), may result in an increase in the level of billrubin in the blood. Levels greater than 3 mg/dl usually are noticeable as jaundice.

Since the billrubin may be elevated in many forms of liver or biliary disease, it is relatively non-specific. It is, however, generally useful as a true liver "function test", since it reflects the liver's ability to take up, process, and secrete billrubin into the bile.

Two other commonly used indicators of liver function are the albumin and the prothrombin time. Albumin is a major protein which is formed by the liver. Although there are many factors which can affect the level of albumin circulating in the blood, chronic liver disease causes a decrease in the amount of albumin produced, and therefore the level of albumin in the blood is reduced. Albumin is also part of most automated chemistry screening panels (normal > 3.5 mg/dl). The prothrombin time (also called the "protime" or PT) is a test that is used to assess blood clotting. Blood clotting factors are proteins made by the liver; when the liver is significantly injured, these proteins are not produced normally. The PT is also a useful liver "function test" since there is a good correlation between abnormalities in coagulation measured by the prothrombin time and the degree of liver dysfunction. The values for the PT are usually expressed in seconds and compared to a control patient's blood (normal +/- 2 seconds of control).

Highly specialized tests may be used to indicate more specifically the presence of certain liver diseases. Elevations in the serum iron or its storage protein ferritin may indicate the presence of hemochromatosis. A deficiency of ceruloplasmin is usually seen in patients with 8 copper metabolism disorder called Wilson's disease. Abnormalities in the alpha-1-antitrypsin may indicate the presence of lung and/or liver disease in children and adults. Immunologic tests such as the antimitochondrial antibody may suggest the presence of primary biliary cirrhosis. Caution must be used, however, in inferring the presence of disease with a blood test. In the case of primary biliary cirrhosis (PBC), up to 15% of patients never form antimitochondrial antibody; and perhaps more significantly, antimitochondrial antibody may be seen in some patients with chronic active hepatitis, or obstruction of the biliary tree, who never develop PBC.

Liver tests provide a useful tool for beginning the investigation of disorders of the liver and biliary system. Interpretation of these tests is a sophisticated process that your physicians place in the context of your history, physical exam, and other tests available to them.

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