Liver function Tests What are liver tests? Liver tests (LTs) 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.

Hepatitis Meaning literally inflammation of the liver, hepatitis refers to a group of conditions, most of which are caused by one of many viruses. Hepatitis can also be inherited (congenital hepatitis) or brought on by excess alcohol consumption. Viral hepatitis is often cleared from the body by the immune system in a period ranging from weeks to months, but when it is not (chronic hepatitis), it must be managed medically. The most well-known forms of hepatitis are hepatitis B and hepatitis C because of the liver damage caused by their chronic forms.

Cirrhosis Cirrhosis, scarring of the liver caused by injury over a period of time, is a consequence of chronic hepatitis, excessive alcohol use, and other less common causes including infections, drug toxins, and inherited diseases. The liver is unique in its ability to regenerate in response to injury. However, with repeated injury over time the liver becomes unable to function properly and scarring develops. This is known as cirrhosis of the liver. As cirrhosis worsens, almost all liver function is lost and the organ becomes harder and smaller. In the absence of a healthy liver, fluid accumulates in the abdomen and legs. Bile salts can build up in the skin causing itching and jaundice. Bleeding from large veins in the esophagus and GI tract may occur. Toxins can accumulate in the blood resulting in mental slowing and confusion.

Liver Enzymes Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) Perhaps the most commonly used indicators of liver (hepatocellular) damage are the alanine aminotransferase (ALT) and aspartate aminotransferase (AST), formerly referred to as the SGPT and SGOT. These are enzymes normally found in liver cells, 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 even in the presence of cirrhosis (liver scarring). Reference values for ALT are less than 36U/L and for AST are less than 42U/L.

Alkaline phosphatase 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 (PBC) 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 gamma-glutamyl transpeptidase (GGT) or 5'- nucleotidase (5'-NT), along with the alkaline phosphatase when the origin of the elevated alkaline phosphatase is not clear. Abnormalities of the 5'-NT or GGT would then suggest liver or biliary tract disease. A normal ALP is between g/L.

Bilirubin Bilirubin is the main bile pigment in humans which, when elevated causes the yellow discoloration of the skin called jaundice. Bilirubin is formed primarily from the breakdown of heme. It is taken up from the blood, processed, and then secreted into the bile by the liver. There is normally a small amount of bilirubin in the blood in healthy individuals (<20µmol/L). Conditions which cause increased formation of bilirubin, 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 bilirubin in the blood. Levels greater than 50 µmol/L usually are noticeable as jaundice. Since the bilirubin 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 bilirubin into the bile. Normal values for total plasma bilirubin are quoted as less than 20 umol/L.

Total protein: Total protein should be between 63-80g/L and reflects the synthetic functions of the liver Albumin 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. (normal > 35 g/L).

Tests of protein metabolism Serum total protein (TP),albumin (A) and globulin (G) The normal range of TP, A and G is 60-80g/L, 40-55g/L and g/L. The normal ratio of A to G (A/G) is Increased G and decreased A (reversed A/G) can be seen in chronic hepatitis, cirrhosis, hepatic neoplasm.

Gamma Glutamyl Transpeptidase (GGT): GGT enzyme is found in certain liver cells and bile duct cells. It is also elevated in diseases that decrease or obstruct the flow of bile. Alcohol abuse, warfarin (a blood-thinner) and drugs used for epilepsy can increase GGT levels. GGT has been used to detect chronic alcohol abuse.epilepsy GGT should be less than 60U/L in a normal individual.

Prothrombin time and INR (International Normalized Ratio) The prothrombin time (also called the “protime” or PT) and the INR are tests 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 and INR are also useful liver function tests since there is a good correlation between abnormalities in coagulation measured by these tests 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).

Other Liver Tests Highly specialized tests may be used to indicate more specifically the presence of certain liver diseases. For example: Specific antibodies, proteins, and nucleic acids may be used to indicate the presence of viral hepatitis B (HBsAg, HBV DNA) or C (eg. anti-HCV antibodies, HCV RNA). Elevations in the serum iron, transferrin saturation and ferritin may indicate the presence of hemochromatosis. A deficiency of ceruloplasmin is usually seen in patients with a copper metabolism disorder called Wilson disease. A low level of alpha-1-antitrypsin may indicate the presence of lung and/or liver disease in children and adults due to alpha-1-antitrypsin deficiency. Immunologic tests such as the antimitochondrial antibody may suggest the presence of primary biliary cirrhosis (PBC). Antinuclear and/or anti-smooth muscle antibodies may indicate the presence of autoimmune hepatitis.

Tests of viral hepatitis Viral hepatitis is caused by five main viruses: hepatitis viruses A, B, C, D and E. In present, hepatitis A, hepatitis B and hepatitis C are more common. The ability to detect the presence of viral components in hepatitis B and C and antibodies to components of hepatitis A,B, C and D has enabled considerable progress to be made in the study of the epidemiology of viral hepatitis. These so-called viral markers can be diagnostic of the cause of acute viral hepatitis.