Introduction to liver blood testAn initial step in detecting liver damage is a simple blood test to determine the presence of certain liver enzymes (proteins) in the blood. Under normal circumstances, these enzymes reside within the cells of the liver. But when the liver is injured for any reason, these enzymes are spilled into the blood stream. Enzymes are proteins that are present throughout the body, each with a unique function. Enzymes help to speed up (catalyze) routine and necessary chemical reactions in the body.
Among the most sensitive and widely used liver enzymes are the aminotransferases. They include aspartate aminotransferase (AST or SGOT) and alanine aminotransferase (ALT or SGPT). These enzymes are normally contained within liver cells. If the liver is injured or damaged, the liver cells spill these enzymes into the blood, raising the enzyme levels in the blood and signaling the liver disease.
What are the aminotransferases?
The aminotransferases catalyze chemical reactions in which an amino group (amino acids are building blocks of proteins) is transferred from a donor molecule to a recipient molecule. Hence, the names "aminotransferases."
Medical terms can sometimes be confusing, as is the case with these enzymes.
* Another name for aminotransferase is transaminase.
* The enzyme aspartate aminotransferase (AST) is also known as serum glutamic oxaloacetic transaminase (SGOT); and
* alanine aminotransferase (ALT) is also known as serum glutamic pyruvic transaminase (SGPT).
To put matters briefly, AST = SGOT and ALT = SGPT.
Normally, where are the aminotransferases?
AST (SGOT) is normally found in a diversity of tissues including liver, heart, muscle, kidney, and brain. It is released into serum when any one of these tissues is damaged. For example, its level in serum rises with heart attacks and with muscle disorders. It is therefore, not a highly specific indicator of liver injury.
ALT (SGPT) is, by contrast, normally found largely in the liver. This is not to say that it is exclusively located in liver, but that is where it is most concentrated. It is released into the bloodstream as the result of liver injury. It therefore serves as a fairly specific indicator of liver status.
What are normal levels of AST and ALT?
The normal range of values for AST (SGOT) is from 5 to 40 units per liter of serum (the liquid part of the blood).
The normal range of values for ALT (SGPT) is from 7 to 56 units per liter of serum.
The ranges of AST and ALT numbers may differ slightly depending on the technique and protocols used by different laboratories. However, normal reference ranges are routinely provided by each laboratory and printed in the report.
What do elevated liver tests (AST and ALT) mean?
AST (SGOT) and ALT (SGPT) are sensitive indicators of liver damage or injury from different types of disease. But it must be emphasized that higher-than-normal levels of these liver enzymes should not be automatically equated with liver disease. They may mean liver problems or they may not. For example, elevations of these enzymes can occur with muscle damage. The interpretation of elevated AST and ALT levels depends upon the entire clinical evaluation of an individual, and so it is best done by physicians experienced in evaluating liver disease and muscle disease.
Moreover, the precise levels of these enzymes do not correlate well with the extent of liver damage or the prognosis (outlook). Thus, the exact levels of AST (SGOT) and ALT (SGPT) cannot be used to determine the degree of liver disease or predict the future. For example, individuals with acute viral hepatitis A may develop very high AST and ALT levels (sometimes in the thousands of units/liter range). But most people with acute viral hepatitis A recover fully without residual liver disease. To the contrary, people with chronic hepatitis C infection typically have only a little elevation in their AST and ALT levels. Some of these individuals may have quietly developed chronic liver disease such as chronic hepatitis and cirrhosis (advanced scarring of the liver).
It is, therefore, worth mentioning that these liver enzymes do not give an indication of the function of the liver. Sometimes they are mistakenly referred to as “liver function tests” or LFTs, but it is a misnomer commonly used even by most physicians.
What liver diseases cause abnormal aminotransferase levels?
Abnormal liver tests may be detected in the blood in a variety of liver conditions.
The highest levels of AST and ALT are found with disorders that cause the death of numerous liver cells (extensive hepatic necrosis). This occurs in such conditions as:
* acute viral hepatitis A or B,
* profound liver damage inflicted by toxins as from an overdose of acetaminophen (brand-name Tylenol), and
* prolonged collapse of the circulatory system (shock) when the liver is deprived of fresh blood bringing oxygen and nutrients.
AST and ALT serum levels in these situations can range anywhere from ten times the upper limits of normal to thousands of units/liter.
Mild to moderate elevations of the liver enzymes are commonplace. They are often unexpectedly encountered on routine blood screening tests in otherwise healthy individuals. The AST and ALT levels in such cases are usually between twice the upper limits of normal and several hundred units/liter.
One of the most common cause of mild to moderate elevations of these liver tests is a condition called fatty liver. In the United States, the most frequent cause of fatty liver is alcohol abuse. Other causes of fatty liver include diabetes mellitus and obesity. Chronic hepatitis C is also becoming an important cause of mild to moderate liver enzyme elevations.
What medications cause abnormal aminotransferase levels?
A host of medications can cause abnormal liver enzymes levels.
Examples include:
Pain relief medications such as:
* aspirin,
* acetaminophen (Tylenol),
* ibuprofen (Advil, Motrin),
* naproxen (Naprosyn, Naprelan, Anaprox, Aleve),
* diclofenac (Voltaren, Cataflam, Voltaren-XR), and
* phenylbutazone (Butazolidine)
Anti-seizure medications such as:
* phenytoin (Dilantin),
* valproic acid (Depakote, Depakote ER, Depakene, Depacon),
* carbamazepine (Tegretol, Tegretol XR, Equertro), and
* phenobarbital
Antibiotics such as:
* tetracyclines, [for example, tetracycline (Achromycin)]
* sulfonamides,
* isoniazid (INH) (Nydrazid, Laniazid)
* sulfamethoxazole (Gantanol),
* trimethoprim (Trimpex; Proloprim, Primsol)
* nitrofurantoin (Macrodantin; Furadantin; Macrobid),
* fluconazole (Diflucan ) and some other anti-fungals, etc.
Cholesterol lowering drugs such as:
* the statins:
o lovastatin (Mevacor, Altocor),
o pravastatin (Pravachol),
o atorvastatin (Lipitor),
o fluvastatin (Lescol),
o rosuvastatin (Crestor),
o simvastatin (Zocor), and
* niacin
Cardiovascular drugs such as:
* amiodarone (Cordarone),
* hydralazine (Apresoline)
* quinidine (Quinaglute, Quinidex), etc.
Other drugs
* Antidepressant drugs of the tricyclic type
With drug-induced liver enzyme abnormalities, the enzymes usually normalize weeks to months after stopping the medications.
What are less common causes of elevated liver blood tests?
Less common causes of abnormal liver enzymes in the United States include chronic hepatitis B, hemachromatosis (iron overload), Wilson's disease, alpha-1-antitrypsin deficiency, celiac sprue, Crohn's disease, ulcerative colitis, and autoimmune hepatitis. Though not as common as hepatitis C, hepatitis B can cause chronic liver disease with persistently abnormal liver enzymes.
* Hemachromatosis is a genetic (inherited) disorder in which there is excessive absorption of dietary iron leading to accumulation of iron in the liver with resultant inflammation and scarring of the liver.
* Wilson's disease is an inherited disorder with excessive accumulation of copper in diverse tissues including the liver and the brain. Copper in liver can lead to chronic liver inflammation, while copper in brain can cause psychiatric and motor disturbances.
* Alpha-1-antitrypsin deficiency is an inherited disorder in which the lack of a glycoprotein (carbohydrate-protein complex) called alpha-1-antitrypsin lead to chronic lung disease (emphysema) and liver disease.
* Autoimmune hepatitis results from liver injury brought about by the body's own antibodies and defense systems attacking the liver.
* Celiac sprue is a disease of the small intestine where a person has an allergy to gluten and develops gas, bloating, diarrhea, and in advanced cases malnutrition. Patients' with celiac sprue can also develop mildly abnormal ALT and AST levels.
* Crohn's disease and ulcerative colitis are diseases with chronic inflammation of the intestines (also referred to as inflammatory bowel diseases). In these individuals inflammation of the liver (hepatitis) or bile ducts (primary sclerosing cholangitis) also can occur, causing abnormal liver tests.
Rarely, abnormal liver enzymes can be a sign of cancer in the liver. Cancer arising from liver cells is called hepatocellular carcinoma or hepatoma. Cancers spreading to the liver from other organs (such as colon, pancreas, stomach, etc) are called metastatic malignancies (to the liver).
How are healthy people evaluated for mild to moderate rises in aminotransferase levels?
Evaluation of healthy individuals with abnormal liver enzymes needs to be individualized. A health care practitioner may ask for the individual's blood test data from old records for comparison. If no old records are available, the health care practitioner may repeat blood tests in weeks to months to see whether these abnormalities persist. He/she will search for risk factors for hepatitis B and C, including sexual exposures, history of blood transfusions, injectable drug use, and occupational exposure to blood products. A family history of liver disease may raise the possibility of inherited diseases such as hemachromatosis, Wilson's disease, or alpha-1- antitrypsin deficiency.
A complete list of routine medications including over-the-counter medications needs to be reviewed as well. A complete physical examination by the health care practitioner is another important part of the evaluation of abnormal liver tests.
The pattern of liver enzyme abnormalities can provide useful clues to the cause of the liver disease. For example, the majority of people with alcoholic liver disease have enzyme levels that are not as high as the levels reached with acute viral hepatitis, and the AST tends to be above the ALT. Thus, in alcoholic liver disease, AST is usually under 300 units/liter while the ALT is usually under 100 units/ liter.
If alcohol or medication is responsible for the abnormal liver enzyme levels, stopping alcohol or the medication (under a health care pracitioner's supervision only) should bring the enzyme levels to normal or near normal levels in weeks to months. If obesity is suspected as the cause of fatty liver, weight reduction of 5% to 10% should also bring the AST and ALT liver blood tests to normal or near normal levels.
If abnormal liver enzymes persist despite abstinence from alcohol, weight reduction, and stopping certain suspected drugs, other tests can be performed to help diagnose possible treatable liver diseases. The blood can be tested for the presence of hepatitis B and C virus and their related antibodies. Blood levels of iron, iron saturation, and ferritin (another measure of the amount of iron stored in the body) are usually elevated in individuals with hemachromatosis. Blood levels of a substance called ceruloplasmin are usually decreased in people with Wilson's disease. Blood levels of certain antibodies (anti- nuclear antibody or ANA, anti-smooth muscle antibody, and anti-liver and kidney microsome antibody) are elevated in individuals with autoimmune hepatitis.
Ultrasound and CAT scan of the abdomen are sometimes used to exclude tumors in the liver or other conditions such as gallstones or tumors obstructing the ducts that drain the liver.
Liver biopsy is a procedure where a needle is inserted through the skin over the right upper abdomen to obtain a thin strand of liver tissue for examination under a microscope. The procedure is oftentimes performed after ultrasound study has located the liver. Not everybody with abnormal liver enzymes needs a liver biopsy. The doctor will usually recommend this procedure if:
1. the information obtained from the liver biopsy will likely be helpful in planning treatment,
2. the doctor needs to know the extent and severity of liver inflammation/damage,
3. effectiveness of a certain treatment requires close monitoring at the tissue level, or
4. no obvious cause of elevated liver tests has been found despite thorough investigation.
Liver biopsy is most useful in confirming a diagnosis of a potentially treatable condition. These potentially treatable liver diseases include chronic hepatitis B and C, hemachromatosis, Wilson's disease, autoimmune hepatitis, and alpha-1-antitrypsin deficiency.
How about monitoring liver blood tests?
What is usually most helpful is serial testing of AST (SGOT) and ALT (SGPT) over time to determine whether the levels are increasing, remaining stable, or decreasing. For example, individuals undergoing treatment for chronic hepatitis C should be monitored with serial liver enzyme tests. Those responding to treatment will experience lowering of liver enzyme levels to normal or near normal levels. Those who develop relapse of hepatitis C after completion of treatment will usually develop abnormal liver enzyme levels again.
What about other liver enzymes?
Aside from AST and ALT, there are other enzymes including alkaline phosphatase, 5'-nucleotidase ("5 prime" nucleotidase), lactate dehydrogenase (LDH), and gamma-glutamyl transpeptidase (GGT) that are often used to detect for liver disease. LDH is not specific to the liver and can be evaluated in many diseases with inflammation in other tissues.
Alkaline phosphatase is a liver enzyme that is frequently measured. This enzyme is usually found in the walls of the intra- and extra-biliary ducts (tube like structures within the liver that connect liver cells together). Elevation of alkaline phosphatase may indicate an injury to the biliary cells. Common causes of biliary injury or biliary obstruction (cholestasis) of this are gallstones and certain mediations, although, some of the conditions listed previously can also raise the levels of this enzyme. Alkaline phosphate is also found in the bone and therefore it can be elevated in bone diseases. GGT and 5' nucleotidase levels can be elevated in biliary conditions (disease of the gallbladder and bile ducts) along with alkaline phosphatase.
REFERENCE: Fauci, Anthony S., et al. Harrison's Principles of Internal Medicine. 17th ed. United States: McGraw-Hill Professional, 2008.
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