Liver Tests Information

Liver Function Tests

Liver function tests represent a broad range of normal functions performed by the liver. The diagnosis of liver disease depends upon a complete history, complete physical examination, and evaluation of liver function tests and further invasive and noninvasive tests. Many patients become confused regarding the meaning of a liver function test. This section is designed to describe the basic liver function tests and the meaning for patients.

The hepatobiliary tree represents hepatic cells and biliary tract cells. Inflammation of the hepatic cells results in elevation in the alanine aminotransferase (ALT), aspartate aminotransferase (AST) and possibly the bilirubin. Inflammation of the biliary tract cells results predominantly in an elevation of the alkaline phosphatase. In liver disease there are crossovers between purely biliary disease and hepatocellular disease. To interpret these, the physician will look at the entire picture of the hepatocellular disease and biliary tract disease to determine which is the primary abnormality.

Alanine Aminotransferase (ALT)

ALT is the enzyme produced within the cells of the liver. The level of ALT abnormality is increased in conditions where cells of the liver have been inflamed or undergone cell death. As the cells are damaged, the ALT leaks into the bloodstream leading to a rise in the serum levels. Any form of hepatic cell damage can result in an elevation in the ALT. The ALT level may or may not correlate with the degree of cell death or inflammation. ALT is the most sensitive marker for liver cell damage.

Aspartate Aminotransferase (AST)

This enzyme also reflects damage to the hepatic cell. It is less specific for liver disease. It may be elevated and other conditions such as a myocardial infarct (heart attack). Although AST is not a specific for liver as the ALT, ratios between ALT and AST are useful to physicians in assessing the etiology of liver enzyme abnormalities.

Alkaline Phosphatase

Alkaline phosphatase is an enzyme, which is associated with the biliary tract. It is not specific to the biliary tract. It is also found in bone and the placenta. Renal or intestinal damage can also cause the alkaline phosphatase to rise. If the alkaline phosphatase is elevated, biliary tract damage and inflammation should be considered. However, considering the above other etiologies must also be entertained. One way to assess the etiology of the alkaline phosphatase is to perform a serologic evaluation called isoenzymes. Another more common method to asses the etiology of the elevated alkaline phosphatase is to determine whether the GGT is elevated or whether other function tests are abnormal (such as bilirubin)

Alkaline phosphatase may be elevated in primary biliary cirrhosis, alcoholic hepatitis, PSC, gallstones in choledocholithiasis.

Gamma Glutamic Transpeptidase (GGT)

This enzyme is also produced by the bile ducts. However, it is not very specific to the liver or bile ducts. It is used often times to confirm that the alkaline phosphatase is of the hepatic etiology. Certain GGT levels, as an isolated finding, reflect rare forms of liver disease. Medications commonly cause GGT to be elevated. Liver toxins such as alcohol can cause increases in the GGT.

Bilirubin

Bilirubin is a major breakdown product of hemoglobin. Hemoglobin is derived from red cells that have outlived their natural life and subsequently have been removed by the spleen. During splenic degradation of red blood cells, hemoglobin (the part of the red blood cell that carries oxygen to the tissues) is separated out from iron and cell membrane components. Hemoglobin is transferred to the liver where it undergoes further metabolism in a process called conjugation. Conjugation allows hemoglobin to become more water-soluble. The water solubility of bilirubin allows the bilirubin to be excreted into bile. Bile then is used to digest food.

As the liver becomes irritated, the total bilirubin may rise. It is then important to understand the difference between total bilirubin, which has undergone conjugation (that is hepatic cell metabolism), and at portion of bilirubin which has not been metabolized. These two components are called total bilirubin and direct bilirubin. The direct bilirubin fraction is that portion of bilirubin that has undergone metabolism by the liver. When this fraction is elevated, the cause of elevated bilirubin (hyperbilirubinemia) is usually outside the liver. These types of causes are typically gallstones. This type of abnormality is usually treated with surgery (such as a gallbladder removal or choleycystectomy).

If the direct bilirubin is low, while the total bilirubin is high, this reflects liver cell damage or bile duct damage within the liver itself.

Albumin

Albumin is the major protein present within the blood. Albumin is synthesized by the liver. As such, it represents a major synthetic protein and is a marker for the ability of the liver to synthesize proteins. It is only one of many proteins that are synthesized by the liver. However, since it is easy to measure, it represents a reliable and inexpensive laboratory test for physicians to assess the degree of liver damage present in the in any particular patient. When the liver has been chronically damaged, the albumin may be low. This would indicate that the synthetic function of the liver has been markedly diminished. Such findings suggest a diagnosis of cirrhosis. Malnutrition can also cause low albumin (hypoalbuminemia) with no associated liver disease.

Prothrombin time (PT)

Another measure of hepatic synthetic function is the prothrombin time. Prothrombin time is affected by proteins synthesized by the liver. Particularly, these proteins are associated with the incorporation of vitamin K metabolites into a protein. This allows normal coagulation (clotting of blood). Thus, in patients who have prolonged prothrombin times, liver disease may be present. Since a prolonged PT is not a specific test for liver disease, confirmation of other abnormal liver tests is essential. This may include reviewing other liver function tests or radiology studies of the liver. Diseases such as malnutrition, in which decreased vitamin K ingestion is present, may result in a prolonged PT time. An indirect test of hepatic synthetic function includes administration of vitamin K (10mg) subcutaneously over three days. Several days later, the prothrombin time may be measured. If the prothrombin time becomes normal, then hepatic synthetic function is intact. This test does not indicate that there is no liver disease, but is suggestive that malnutrition may coexist with (or without) liver disease.

Platelet Count

Platelets are cells that form the primary mechanism in blood clots. They're also the smallest of blood cells. They derived from the bone marrow from the larger cells known as megakaryocytes. Individuals with liver disease develop a large spleen. As this process occurs platelets are trapped with in the sinusoids (small pathways within the spleen) of the spleen. While the trapping of platelets is a normal function for the spleen, in liver disease it becomes exaggerated because of the enlarged spleen (splenomegaly). Subsequently, the platelet count may become diminished.

Serum Protein Electrophoresis

This is an evaluation of the types of proteins that are present with in a patient's serum. By using an electrophoretic gel, major proteins can be separated out. This results in four major types of proteins. These are 1) albumin, 2) alpha globulins, 3) beta globulins and 4) gammaglobulins. This test is useful for evaluation of patients who have abnormal liver function tests since it allows a direct quantification of multiple different serum proteins. If the gamma globulin fraction is elevated, autoimmune hepatitis may be present. In addition a deficiency in the alpha globulin fraction can result in the diagnosis, or a clinical clue, to A. alpha-1 antitrypsin deficiency. This is a simple blood test that is commonly performed by hepatologists. 

Test Overview OF Viral Hepatitis

Hepatitis A (HAV)

Hepatitis A virus tests detect substances in the blood that indicate a hepatitis infection is active or has occurred in the past. The test detects proteins (antibodies) made by the body in response to the virus that causes hepatitis. It is important to identify the type of hepatitis virus causing infection so that its spread can be prevented and the proper treatment can be started immediately.

Hepatitis A Virus (HAV) Testing

HAV infection is spread through food or water that has been contaminated by the feces (stool) of an infected person.

IgM anti HAV antibodies indicate a recent infection with hepatitis A virus. IgM anti HAV antibodies generally can be detected in the blood as early as 2 weeks after the initial HAV infection. These antibodies disappear from the blood 3 to 12 months after the infection.

IgG anti HAV antibodies mean that you have had a hepatitis A viral infection. About 8 to 12 weeks after the initial infection with hepatitis A virus, IgG anti HAV antibodies appear and remain in the blood for lifelong protection against HAV.

Hepatitis A vaccine is available to prevent an HAV infection. If you have had this vaccine and you have anti HAV antibodies, this means the vaccination was effective.  

Common Hepatitis B Blood Test

HBsAg (hepatitis B surface antigen) - This refers to the outer surface of the hepatitis B virus that triggers an antibody response. A "positive" or "reactive" HBsAg test result means that the person is infected with the hepatitis B virus. This can be an "acute" or a "chronic" infection. Infected people can pass the virus on to others through their blood.

HBsAb or anti-HBs (hepatitis B surface antibody) - This refers to the protective antibody that is produced in response to an infection. It appears when a person has recovered from an acute infection and cleared the virus (usually within six months) or responded successfully to the hepatitis B vaccine shots. A "positive" or "reactive" HBsAb (or anti-HBs) test result indicates that a person is "immune" to any future hepatitis B infection and is no longer contagious. This test is not routinely included in blood bank screenings.

HBcAb or anti-HBc (hepatitis B core antibody) - This refers to an antibody that is produced in response to the core-antigen, a component of the hepatitis B virus. However, this is not a protective antibody. In fact, it is usually present in those chronically infected with hepatitis B. A "positive" or "reactive" HBcAb (or anti-HBc) test result indicates a past or present infection, but it could also be a false positive. The interpretation of this test result depends on the first two test results. Its appearance with the protective surface antibody (positive HBsAb or anti-HBs) indicates prior infection and recovery. For chronically infected persons, it will usually appear with the virus (positive HbsAg).

Hepatitis C (HCV) 

The Each of the five most common tests has a slightly different purpose: 

• Anti-HCV tests detect the presence of antibodies to the virus, indicating exposure to HCV. These tests cannot tell if you still have an active viral infection, only that you were exposed to the virus in the past. Usually, the test is reported as “positive” or “negative.” There is some evidence that, if your test is “weakly positive,” it may not mean that you have been exposed to the HCV virus. The Centers for Disease Control and Prevention (CDC) revised its guidelines in 2003 and suggests that weakly positive tests be confirmed with the next test before being reported. 

• HCV RIBA test is an additional test to confirm the presence of antibodies to the virus. In most cases, it can tell if the positive anti-HCV test was due to exposure to HCV (positive RIBA) or represents a false signal (negative RIBA). In a few cases, the results cannot answer this question (indeterminate RIBA). Like the anti-HCV test, the RIBA test cannot tell if you are currently infected, only that you have been exposed to the virus. 

• HCV-RNA test identifies whether the virus is in your blood, indicating that you have an active infection with HCV. In the past, it was usually performed by a test called a qualitative HCV. Qualitative HCV RNA is reported as a “positive” or “detected” if any HCV viral RNA is found; otherwise, the report will be “negative” or “not detected”. The test may also be used after treatment to see if the virus has been eliminated from the body. 

• Viral Load or Quantitative HCV tests measure the number of viral RNA particles in your blood. Viral load tests are often used before and during treatment to help determine response to treatment by comparing the amount of virus before and after treatment (usually after 3 months); successful treatment causes a decrease of 99% or more (2 logs) in viral load soon after starting treatment (as early as 4-12 weeks), and usually leads to viral load being not detected. Some newer viral load tests can detect very low amounts of viral RNA, and some laboratories no longer do qualitative HCV RNA tests if they use one of these versions of viral load testing. 

• Viral genotyping is used to determine the kind, or genotype, of the virus present. There are 6 major types of HCV; the most common (genotype 1) is less likely to respond to treatment than genotypes 2 or 3 and usually requires longer therapy (48 weeks, versus 24 weeks for genotype 2 or 3). Genotyping is often ordered before treatment is started to give an idea of the likelihood of success and how long treatment may be needed.

• Biopsy. A biopsy is a tiny sample of body tissue -- in this case, liver tissue. The tissue is prepared and stained in a laboratory, so the physician can view it under a microscope. This usually helps the physician make a specific diagnosis and determine the extent and seriousness of the condition. It is vital information for determining treatment.

When is it ordered?

Hepatitis C infection is the most common cause of chronic liver disease in North America; about 2% of all adults in the United States have been exposed to the virus, and 75-85% of those are chronically infected. The CDC recommends HCV testing in the following cases: 

• If you have ever injected illegal drugs 

• If you received a blood transfusion or organ transplant before July 1992* 

• If you have received clotting factor concentrates produced before 1987 

• If you were ever on long-term dialysis 

• For children born to HCV-positive women 

• For health care, emergency medicine, and public safety workers after needlesticks, sharps, or mucosal exposure to HCV-positive blood 

• For people with evidence of chronic liver disease

The blood supply has been monitored in the U.S. since 1990, and any units of blood that test positive for HCV are rejected for use in another person. The current risk of HCV infection from transfused blood is about 1 case per two million transfused units.

A positive anti-HCV test may be confirmed with an HCV RIBA test, especially if the test is “weakly positive.” Qualitative HCV-RNA is often used when the antibody test is positive to see if the infection is still present. HCV viral load and genotyping may be done to plan treatment; viral load and qualitative HCV RNA are also used to monitor response to treatment.

What does the test result mean?

If the antibody test result is positive, you have probably been infected with hepatitis C, even if it was so mild you did not realize you had it.

A positive RIBA confirms that you had been exposed to the virus, while a negative RIBA indicates that your first test was probably a false positive and you have never been infected by HCV.

A positive (or detectable) HCV RNA means that you are currently infected by HCV.

Is there anything else I should know?

HCV antibodies usually do not appear until several months into an infection but will always be present in the later stages of the disease.

Hepatitis D Virus (HDV) Testing

Infection with the hepatitis D virus (HDV), or delta agent, occurs only in people who are already infected with the hepatitis B virus (HBV). Vaccination against hepatitis B will prevent hepatitis D infection. Hepatitis D infection is rare in Canada and the United States, except among people who inject illegal drugs and those who are frequently exposed to blood products. The hepatitis D test detects HDV antibodies. A positive test indicates only that you have been infected with HDV—it cannot distinguish between an acute or chronic infection. Another test, the HDV RNA test, is needed to determine whether you have an active HDV infection. It does not distinguish between an acute or chronic infection. However, this test currently is not available except in research settings.

Since hepatitis B infections can be spread through sexual contact, practise safe sex until your test results are returne.                                    

Detection of HEV and prophylaxis of hepatitis E

Only one serological test to diagnose HEV infection is commercially available (Genelabs Technologies, Singapore). However, several diagnostic tests are available in research laboratories, including: (1) EIAs and western blot assays to detect anti-HEV IgM and IgG in serum (Ref. 47); (2) PCR tests to detect HEV RNA in sera and stools; and (3) immunofluorescent antibody-blocking assays to detect antibody to HEV antigen in the serum and in liver biopsies. However, the sensitivity and specificity of these tests have not been determined independently using a good panel of anti-HEV positive and negative sera.

Hepatitis G virus (HGV) testing

The only method of detecting HGV is a complex and costly DNA test that is not widely available. Efforts are under way, however, to develop a test for the HGV antibody, which is formed in response to invasion by the virus. Once antibody is present, however, the virus itself generally has disappeared, making the test too late to be of use.

Tests

Testing for a virus that does not seem to cause any illness is generally confined to research purposes. Antibodies can be tested for in blood and a PCR test can show the presence of the virus.