The diagnosis of liver diseases depends upon a combination of history, physical examination, laboratory testing and sometimes radiological studies and biopsy. Only a medical provider who knows all of these aspects of a specific case can reliably make a diagnosis. Many individuals with liver diseases nonetheless have questions about their laboratory test results and seek information about their significance.
The term “liver function tests” and its abbreviated form “LFTs” is a commonly used term that is applied to a variety of blood tests that assess the general state of the liver and biliary system. Routine blood tests can be divided into those tests that are true LFTs, such as serum albumin or prothrombin time, and those tests that are simply markers of liver or biliary tract disease, such as the various liver enzymes. In addition to the usual liver tests obtained on routine automated chemistry panels, your medical provider may order more specific liver tests such as viral serologic tests to look for hepatitis C.
Alanine aminotransferase (ALT)
ALT is an enzyme produced in hepatocytes, the major cell type in the liver. ALT is often inaccurately referred to as a liver function test, however, its level in the blood tells little about the function of the liver. The level of ALT in the blood (actually enzyme activity is measured in the clinical laboratory) is increased in conditions in which hepatocytes are damaged or die. As cells are damaged, ALT leaks out into the bloodstream. All types of hepatitis (viral, alcoholic, drug-induced, etc.) cause hepatocyte damage that can lead to elevations in the serum ALT activity. The ALT level is also increased in cases of liver cell death resulting from other causes, such as shock or drug toxicity. The level of ALT may correlate roughly with the degree of cell death or inflammation, however, this is not always the case. An accurate estimate of inflammatory activity or the amount cell death can only be made by liver biopsy. (See also aspartate aminotransferase below.)
Aspartate aminotransferase (AST)
AST is an enzyme similar to ALT (see above) but less specific for liver disease as it is also produced in muscle and can be elevated in other conditions (for example, early in the course of a heart attack). AST is also inaccurately referred to as a liver function test by many physicians. In many cases of liver inflammation, the ALT and AST activities are elevated roughly in a 1:1 ratio. In some conditions, such as alcoholic hepatitis or shock liver, the elevation in the serum AST level may higher than the elevation in the serum ALT level.
Alkaline phosphatase is an enzyme, or more precisely a family of related enzymes, produced in the bile ducts, intestine, kidney, placenta and bone. An elevation in the level of serum alkaline phosphatase (actually enzyme activity is measured in the clinical laboratory), especially in the setting of normal or only modestly elevated ALT and AST activities, suggests disease of the bile ducts. Serum alkaline phosphatase activity can be markedly elevated in bile duct obstruction or in bile duct diseases such as primary biliary cirrhosis or primary sclerosing cholangitis. Alkaline phosphatase is also produced in bone and blood activity can also be increased in some bone disorders.
An enzyme produced in the bile ducts that, like alkaline phosphatase, may be elevated in the serum of patients with bile duct diseases. Elevations in serum GGT, especially along with elevations in alkaline phosphatase, suggest bile duct disease. Measurement of GGT is an extremely sensitive test, however, and it may be elevated in virtually any liver disease and even sometimes in normal individuals. GGT is also induced by many drugs, including alcohol, and its serum activity may be increased in heavy drinkers even in the absence of liver damage or inflammation.
Bilirubin is the major breakdown product that results from the destruction of old red blood cells (as well as some other sources). It is removed from the blood by the liver, chemically modified by a process call conjugation, secreted into the bile, passed into the intestine and to some extent reabsorbed from the intestine. Bilirubin concentrations are elevated in the blood either by increased production, decreased uptake by the liver, decreased conjugation, decreased secretion from the liver or blockage of the bile ducts. In cases of increased production, decreased liver uptake or decreased conjugation, the unconjugated or so-called indirect bilirubin will be primarily elevated. In cases of decreased secretion from the liver or bile duct obstruction, the conjugated or so-called direct bilirubin will be primarily elevated. Many different liver diseases, as well as conditions other than liver diseases (e. g. increased production by enhanced red blood cell destruction), can cause the serum bilirubin concentration to be elevated. Most adult acquired liver diseases cause impairment in bilirubin secretion from liver cells that cause the direct bilirubin to be elevated in the blood. In chronic, acquired liver diseases, the serum bilirubin concentration is usually normal until a significant amount of liver damage has occurred and cirrhosis is present. In acute liver disease, the bilirubin is usually increased relative to the severity of the acute process. In bile duct obstruction, or diseases of the bile ducts such as primary biliary cirrhosis or sclerosing cholangitis, the alkaline phosphatase and GGT activities are often elevated along with the direct bilirubin concentration.
Albumin is the major protein that circulates in the bloodstream. Albumin is synthesized by the liver and secreted into the blood. Low serum albumin concentrations indicate poor liver function. The serum albumin concentration is usually normal in chronic liver diseases until cirrhosis and significant liver damage is present. Albumin levels can be low in conditions other than liver diseases including malnutrition, some kidney diseases and other rarer conditions.
Prothrombin time (PT)
Many factors necessary for blood clotting are made in the liver. When liver function is severely abnormal, their synthesis and secretion into the blood is decreased. The prothrombin time is a type of blood clotting test performed in the laboratory and it is prolonged when the blood concentrations of some of the clotting factors made by the liver are low. In chronic liver diseases, the prothrombin time is usually not elevated until cirrhosis is present and the liver damage is fairly significant. In acute liver diseases, the prothrombin time can be prolonged with severe liver damage and return to normal as the patient recovers. Prothrombin time can also be prolonged in cases of vitamin K deficiency, by drugs (warfarin, used therapeutically as an anti-coagulant, prolongs the prothrombin time) and in non-liver disorders.
Platelets are the smallest of the blood cells (actually fragments of larger cells known as megakaryocytes) that are involved in clotting. In some individuals with liver disease, the spleen becomes enlarged as blood flow through the liver is impeded. This can lead to platelets being sequestered in the enlarged spleen. In chronic liver diseases, the platelet count usually falls only after cirrhosis has developed. The platelet count can be abnormal in many conditions other than liver diseases.
Hepatitis C Antibody Test
This is the first test for determining whether you have been infected with hepatitis C. The results will come back as either positive or negative.
Explanation of test results:
- If this test result is positive, it means your body was exposed to the hepatitis C virus and made antibodies. However, it does not tell you whether you are still infected with hepatitis C. If the antibody test result is positive, you should be tested for hepatitis C RNA (see “Hepatitis C RNA”), which determines whether you are chronically infected. The lab might perform this RNA test automatically if your hepatitis C antibody test is positive or your medical provider might need to order the Hepatitis C RNA test separately.
- If the antibody test result is negative, it means you have not been infected with the hepatitis C virus, and further testing for hepatitis C usually is not needed.
Other important things to know:
- After a successful course of treatment for hepatitis C, the hepatitis C antibody remains detectable, but the hepatitis C RNA will be undetectable.
- Any patient with a positive test result for the hepatitis C antibody should have additional tests to determine whether or not the virus is still active.
Hepatitis C Genotype
The hepatitis C genotype is a type or “strain” of hepatitis C virus. There are 6 genotypes of hepatitis C around the world. In the United States, 3 genotypes are common:
- Genotype 1 – most common
- Genotype 2
- Genotype 3
These can be further specified as:
- Genotype 1a or 1b
- Genotype 2a or 2b
- Genotype 3a or 3b
The genotype of hepatitis C does not change over time. It needs to be tested only once. If you are treated for hepatitis C, your genotype will determine your treatment plan, such as which medications are prescribed and how long the treatment will be.
Hepatitis C RNA Qualitative Testing
The qualitative HCV RNA tests use either a process called polymerase chain reaction (PCR) or a process called transcription-mediated amplification (TMA). Either type of qualitative test will report whether the hepatitis C virus is present in the bloodstream or not. The result is reported as either “detected” or “not detected.”
Explanation of test results: If a qualitative RNA test is positive (detected), then it is confirmed that the patient has chronic hepatitis C. The “qualitative” test is more accurate than the “quantitative” test because qualitative tests are able to detect very low levels of the virus.
Other important things to know:
- If a patient has a quantitative test that shows no detectable virus, but has a positive result with the qualitative test, it means there is a very low level of virus that can be detected only with the qualitative test.
- The qualitative test will show a negative result when patients have a successful response to the treatment – cured of hepatitis C
- The qualitative test result also will be negative when patients clear the hepatitis C virus on their own, soon after infection, or “spontaneously.”
Hepatitis C RNA Quantitative Testing
The quantitative HCV RNA tests measure the amount of hepatitis C virus in the blood. The result will be an exact number, such as “1,215,422 IU/L.” Some people refer to the quantitative measurement as the hepatitis C “viral load.”
Explanation of test results: There are 2 situations in which a quantitative test is useful:
The quantitative HCV RNA test is checked before a patient starts treatment:
Knowing the hepatitis C RNA before starting treatment is useful because patients with RNA <6,000,000 IU may only need 8 weeks of treatment with a specific medication.
The quantitative HCV RNA test is used to monitor a patient who is currently on treatment:
The response to treatment is considered good when the quantitative HCV RNA measurement drops and the virus eventually becomes completely undetectable with RNA
Other things to know:
- The viral load measurement does not tell us anything about the severity of a patient’s liver disease or the degree of fibrosis (scarring). For that information, the patient would need a liver biopsy, Fibroscan or fibrosis blood test.
- It is not necessary to check the viral load repeatedly unless a patient is on treatment or is considering treatment.
- If a quantitative HCV RNA results is reported as “<25 IU/L [lower limit of quantification for the blood test],” this means that the quantitative test cannot measure the hepatitis C virus. It may mean that there is no detectable HCV RNA at all and if this is 12 weeks after completing treatment then you are defined as a sustained viral responder [SVR] and you have been cured of hepatitis C.
- If a quantitative HCV RNA results is “<25 IU/L” but the qualitative test is “detected” then the hepatitis C virus is present in the bloodstream, but at a very low level, too low to be measured by a quantitative test.