Liver Blood Tests

The liver is located in the right upper portion of the abdominal cavity just beneath the rib cage. The liver has many functions vital to life. Some of the important functions of the human liver are:

• Detoxification of blood
• Production of important clotting factors, albumin, and many other important proteins
• Metabolizing (processing) medications and nutrients
• Processing of waste products of hemoglobin and other cells
• Storing of vitamins, fat, cholesterol, and bile
• Production of glucose (gluconeogenesis or glucose synthesis/release during starvation)

Liver blood tests are some of the most commonly performed blood tests. These tests can be used to assess liver functions or liver injury. An initial step in detecting liver damage is a simple blood test to determine the level of certain liver enzymes (proteins) in the blood. Under normal circumstances, these enzymes mostly reside within the cells of the liver. But when the liver is injured for any reason, these enzymes are spilled into the bloodstream. Enzymes are proteins that are present throughout the body, each with a unique function. Enzymes help to speed up (catalyze) routine and vital chemical reactions in the body.

Among the most sensitive and widely used liver enzymes are aminotransferases. They include aspartate aminotransferase (AST or SGOT) and alanine aminotransferase (ALT or SGPT). These enzymes are normally predominantly contained within liver cells and to a lesser degree in muscle cells. If the liver is injured or damaged, the liver cells spill these enzymes into the blood, raising the AST and ALT enzyme blood levels and signaling liver disease.

Other blood tests about the liver are measurements of some of the other enzymes found in the liver. In addition to AST and ALT, alkaline phosphatase, 5' nucleotidase, and gamma-glutamyl transpeptidase (GGT) are a few of the other enzymes located in the liver. The focus of this article is mainly on the most common liver enzymes, AST and ALT.

The aminotransferase enzymes catalyze chemical reactions in which an amino group from one amino acid (amino acids are building blocks of proteins) is transferred from a donor molecule to a recipient molecule, hence, the name "aminotransferases."

Medical terms can sometimes be confusing, as is the case with these enzymes because they have interchangeable names that commonly appear in both medical and non-medical articles. For example:

• Another name for aminotransferase is transaminase.
• The enzyme aspartate aminotransferase (AST) is also known as serum glutamic oxaloacetic transaminase (SGOT).
• Alanine aminotransferase (ALT) is also known as serum glutamic pyruvic transaminase (SGPT).

So, AST = SGOT and ALT = SGPT are enzymes produced by the liver and other types of cells.

AST (SGOT) is normally found in a variety of tissues including the liver, heart, muscle, kidney, and brain. It is released into the blood (serum) when any one of these tissues is damaged. For example, the AST level in serum is elevated in heart attacks or with a muscle injury. It is not a highly specific indicator of liver injury as its elevation can occur as a result of other injured tissues.

ALT (SGPT) is, by contrast, normally found largely in the liver. It is not exclusively located in the liver, but that is where it is most concentrated. It is released into the bloodstream as the result of liver injury so it serves as a fairly specific indicator of liver status.

• The normal range of values for AST (SGOT) is about 5 to 40 units per liter of serum (the liquid part of the blood).
• The normal range of values for ALT (SGPT) is about 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 worldwide. Normal reference ranges are routinely provided by each laboratory and printed with each patient's report.

AST (SGOT) and ALT (SGPT) are reasonably sensitive indicators of liver damage or injury from different types of diseases or conditions, and collectively they are termed liver tests or liver blood tests. However, higher-than-normal levels of these liver enzymes are not 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 results 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 liver enzyme tests do not correlate well with the extent of liver problems or the prognosis (outlook) so, the exact levels of AST (SGOT) and ALT (SGPT) cannot be used to determine the degree of liver disease or predict the future prognosis for liver function. 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. Conversely, people with chronic hepatitis C infection typically have only a little elevation in their AST and ALT levels while having a substantial liver injury and even advanced scarring of the liver (cirrhosis) from ongoing minor inflammation of the liver.

It is important to clarify that ALT and AST levels do not completely reflect the function of the liver, even though in the medical community and medical publications they commonly are referred to as liver function tests. Even in conditions when AST and ALT are very elevated, the liver still may function properly.

Consequently, if you have "elevated liver enzymes" or a high or abnormal liver test, you need to ask your physician exactly what all the tests indicate.

The blood tests that truly reflect liver function are the following; normal values (ranges) listed are for adult men - women and children have similar but slightly different ranges of normal test values.

• Coagulation panel (prothrombin time or PT, and international normalized ratio or INR): These tests measure blood's ability for normal clotting and prevention of bleeding and bruising. This is the function of certain proteins called clotting factors that normally are produced in the liver. Normal values are about 9.5 to 13.8 seconds.
• Albumin level (hypoalbuminemia): Albumin is a very common protein found in the blood with a variety of functions. It also is produced only in the liver, and if its levels are lower than normal it can be suggestive of chronic liver disease or liver cirrhosis. Many conditions other than liver disease also may cause low albumin levels. Normal values are about 3.5 to 5 g/dL.
• Bilirubin: This molecule is a byproduct of the routine destruction of red blood cells occurring in the liver. It is normally released as bile in the feces. Elevation of the bilirubin can suggest liver dysfunction. However, other conditions with increased destruction of red blood cells also can cause elevated bilirubin levels despite normal liver function. Normal values are about 0.1 to 1.0 mg/dL.

• Platelet count: Low platelet count (thrombocytopenia) has many causes, one of which can be advanced liver disease. Normal platelet counts are about 150,000 to 400,000 per (µL).
• Glucose: Glucose level is maintained in the body by a variety of mechanisms. The liver can release glucose in the blood for nourishment of other cells in case of starvation with insufficient oral intake of glucose. This process, called gluconeogenesis, is another major function of the liver. In advanced liver disease, this function of the liver can be compromised leading to unusually low glucose levels in the absence of adequate oral intake. Conversely, a large number of people with liver cirrhosis become glucose intolerant and develop diabetes.
• GGT (Gamma-glutamyl transpeptidase): This enzyme is thought to indicate possible liver damage; the higher the abnormal level, the more likely there is liver damage. Normal levels of GGT are about 9 to 48 U/L.
• ALP (alkaline phosphatase): The liver synthesizes the highest amounts of this enzyme so high levels in the blood may suggest liver injury among other causes. Normal levels of ALP are about 45 to 115 U/L.
• LD or LDH (Lactate dehydrogenase): This enzyme may be elevated in many types of diseases, including liver disease. Normal levels are about 122 to 222U/L.

Many hospitals and doctor's offices list a liver function panel as part of a lab workup. These panels vary and may consist of AST, ALT, and some or all of the tests listed above. In addition, the normal panel values may vary somewhat, especially between adult men, women, and children so viewing the "normal" ranges of test values is always recommended, and a thorough discussion with the physician is necessary. In addition, some clinicians recommend other tests such as serum ammonia and serum lactate levels in their panels.

There are home liver tests for blood enzyme levels and liver function, however, individuals who use these tests should first discuss their use and results with their healthcare professional.

Abnormal liver tests may be detected in the blood in a variety of liver conditions.

• Mild to moderate elevations of liver enzymes are common. They are often unexpectedly encountered on routine blood screening tests in otherwise healthy individuals. The AST and ALT readings in such cases are usually between twice the upper limits of normal and several hundred units/liter.
  • One of the most common causes of mild to moderate elevations of these liver tests is a condition referred to as fatty liver (steatohepatitis or hepatic steatosis). In the United States, the most frequent cause of fatty liver is alcohol abuse.
  • Other causes of fatty liver include diabetes mellitus and obesity. Fatty liver tests are composed of several tests including blood tests, CT and/or MRI tests, and in some individuals, a liver biopsy.
• Chronic hepatitis B and hepatitis C are other causes of chronic mild to moderate liver enzyme elevation. In these conditions, ALT and AST may be only slightly high and the degree of abnormality in liver function tests can indicate the degree of injury.
• Chronic and acute alcohol use also can commonly cause abnormal liver blood tests.
  • In alcoholic hepatitis, the range of liver tests can vary greatly.
  • In chronic alcohol liver disease or alcoholic cirrhosis, a slight elevation of ALT and AST may be observed.
  • In acute alcoholic hepatitis, high liver enzyme numbers are often seen.
• Many medications can be responsible for a mild to moderate increase in liver enzyme tests.

A variety of medications can cause abnormal liver enzyme levels in some individuals.

Examples of some of the common medications with potential liver toxicity include:

• Pain relief medications such as:
  • aspirin,
  • acetaminophen (Tylenol and others),
  • 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), and
  • fluconazole (Diflucan) and some other anti-fungals, etc.
• Cholesterol-lowering drugs such as statins:
  • lovastatin (Mevacor, Altocor),
  • pravastatin (Pravachol),
  • atorvastatin (Lipitor),
  • fluvastatin (Lescol),
  • simvastatin (Zocor),
  • rosuvastatin (Crestor), and
  • niacin.
• Cardiovascular drugs such as:
  • amiodarone (Cordarone),
  • hydralazine (Apresoline), and
  • quinidine (Quinaglute, Quinidex), etc.
• Other drugs such as:
  • antidepressant drugs of the tricyclic type.

With drug-induced liver enzyme abnormalities, the enzymes usually normalize weeks to months after stopping the medications. Typically, the physician will want to monitor the patient's liver enzymes over time to confirm that the values are normalizing.

AST and ALT serum levels in some liver conditions can range anywhere from ten times the upper limits of normal to thousands of units/liter. The highest levels of AST and ALT are found with disorders that cause the rapid death of numerous liver cells (extensive hepatic necrosis). Although this degree of liver enzyme elevation is not common, it can occur in such conditions as:

• Acute viral hepatitis A or B
• Profound liver damage inflicted by toxins from an overdose of acetaminophen (Tylenol) or mushroom poisoning
• The prolonged collapse of the circulatory system (shock) when the liver is deprived of fresh blood providing oxygen and nutrients

Also, very high AST and ALT levels can be a result of severe muscle diseases.

Less common causes of abnormal liver enzymes in the United States include hemochromatosis (iron overload), Wilson's disease, alpha-1-antitrypsin deficiency, celiac disease, 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.

• Hemochromatosis is a genetic (inherited) disorder in which there is excessive absorption of dietary iron leading to the accumulation of iron in the liver with resultant inflammation and scarring of the liver. If undiagnosed or untreated, hemochromatosis can progress to cirrhosis and liver failure.
• Wilson's disease is an inherited disorder with excessive accumulation of copper in diverse tissues including the liver and the brain. Excess copper in the liver can lead to chronic liver inflammation, while copper in the 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 leads to chronic lung disease (emphysema) and chronic liver disease.
• Autoimmune hepatitis results from liver injury brought about by the body's antibodies and defense systems attacking the liver.

• ?????Celiac disease (celiac sprue) is a disease of the small intestine where a person has an immune response to gluten and develops gas, bloating, diarrhea, and in advanced cases, malnutrition. Patients with celiac disease can also develop mildly abnormal ALT and AST levels.
• Crohn's disease and ulcerative colitis are diseases with chronic inflammation of the intestines (collectively referred to as inflammatory bowel diseases or IBD). In these individuals, inflammation of the liver (hepatitis) or bile ducts (primary sclerosing cholangitis) also can occur, causing abnormal liver tests.
• Viral infections other than common hepatitis viruses (A, B, C) can sometimes cause an elevation of liver enzymes as they can result in generalized body infection and liver inflammation.
• Non-viral infections of the liver are rare, but they can cause liver damage. Bacterial and amebic (parasitic) hepatic (liver) abscesses typically present as focal infection and inflammation of the liver as opposed to viral hepatitis where generalized liver inflammation occurs. Liver enzyme elevation is usually seen in the setting of these infections.
• Rarely, abnormal liver enzymes can be a sign of liver cancer. Cancer arising from liver cells is called hepatocellular carcinoma or hepatoma. Cancers spreading to the liver from other organs (such as the colon, pancreas, stomach, and others) are called metastatic malignancies (to the liver).
• Liver hemangiomas (masses of abnormal and atypical blood vessels within the liver) are the most common tumors in the liver. However, hepatic hemangiomas are benign and in general, do not cause elevation of liver tests.
• Another rare condition that causes liver test elevation is the Budd-Chiari Syndrome. In this condition, obstruction of blood flow in the liver by a blood clot can damage the liver by limiting blood flow leading to injury of liver cells. As a result of this insult, liver enzymes may rise indicating hepatic inflammation.
• Glycogen storage disorders are genetic conditions seen in the pediatric population (detected at birth in severe types or later in childhood in less severe types). They impair the ability of the liver to store and metabolize glycogen, a complex sugar necessary for the production of nutrients and energy in the body. Glycogen storage disorders cause varying degrees of liver enzyme abnormalities.

The above list is not comprehensive and other less common conditions can also cause elevated liver blood tests. If you have elevated liver blood tests, working with your healthcare provider to identify the underlying cause and develop an appropriate treatment plan is important.

The following risk factors may increase the chances of developing liver disease.

• Toxin exposure: Some household chemicals can pass into your bloodstream and harm your liver. Toxins can also come from pesticides used on foods you eat or compounds in your work environment.
• Supplements: Various herbs and supplements can end up causing problems for your liver.
• Alcohol consumption: Drinking too much alcohol can cause your liver to swell, resulting in scarring and damage that may be permanent.
• Other health problems that can lead to potential liver issues include being overweight/obese, diabetes, or high cholesterol levels. You may be more prone to liver problems if there is a family history of liver disease.

Some warning signs and symptoms of malfunctioning liver include:

• Constant fatigue or uneasiness.
• Dull pain in your abdomen: one of the first signs of a potentially serious problem.
• Jaundice, yellowing of the skin and whites of the eyes occurs when your liver fails to remove bilirubin from the body.
• Bleeding or easy bruising that can occur when the liver fails to produce adequate blood clotting proteins.
• Edema (swelling of the legs with fluid) occurs when the liver can't produce enough albumin, leading to low albumin in the blood.
• Fatigue is of unknown cause, but it may be associated with a weakened metabolic function of the liver.
• When the liver is malfunctioning, toxins build up in the blood and can travel to the brain, affecting brain function and leading to confusion, disorientation, or forgetfulness.
• Because the bilirubin is usually excreted through the kidney, it turns the urine a dark color.
• Because the bile production is usually declined or the flow of bile out of the liver is blocked in a malfunctioned liver, stools usually turn clay-colored.
• When toxins build up, they cause digestive distress, leading to nausea and vomiting.
• Because the liver plays an important role in the maintenance of the digestive system, a malfunctioning liver can cause loss of appetite.
• The association between sleepiness and a malfunctioning liver is complex, but various mechanisms are thought to be involved.

The evaluation of healthy individuals with abnormal liver enzymes needs to be individualized. A doctor may ask for the patient's blood test data from old records for comparison. If no old records are available, the doctor may repeat blood tests in weeks to months to see whether abnormalities persist.

In the meantime, along with a physical examination and a thorough medical history, the doctor will search for potential infectious and non-infectious causes and risk factors for liver disease such as:

• Medications
• Alcohol use
• Sexual exposures
• History of blood transfusions
• History of injectable drug use
• Occupational exposure to blood products
• Family history of liver disease (for the possibility of inherited diseases such as hemochromatosis, Wilson's disease, or alpha-1-antitrypsin deficiency).

A complete list of routine medications including over-the-counter medications will be reviewed.

Signs and symptoms of liver disease may or may not be present in individuals with mild increases in liver enzymes. Signs of liver damage can include:

• Jaundice (yellowing of skin and eyes)
• Easy bruising
• Ascites (distention of the abdomen as a result of retained fluid)
• Enlarged spleen (splenomegaly)
• Confusion

Symptoms of liver disease are non-specific and numerous. Some of the more common liver disease symptoms may include fatigue, itching, yellow skin, poor appetite, and abdominal discomfort.

The pattern of liver enzyme abnormalities can sometimes provide useful clues as to the cause of the liver condition. For example, in a majority of people with alcoholic liver disease, liver enzyme levels are not as high as the levels reached in acute viral hepatitis.

• In alcoholic liver disease, frequently AST tends to be higher (usually under 300 units/liter) than ALT (usually under 100 units/ liter).

If alcohol or medication is responsible for the abnormal liver enzyme tests, stopping alcohol or the culprit medication (under a health care professional'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 disease, weight reduction of about 5% to 10% should also bring the AST and ALT liver blood tests to normal or near-normal levels in some individuals.

If abnormal liver enzymes persist despite abstinence from alcohol, weight reduction, and stopping certain suspected drugs, other tests can be performed to help diagnose other possible treatable liver diseases. The blood can be tested for the presence of hepatitis B and C viruses and their related antibodies. Blood levels of iron, iron saturation, and ferritin (another measurement of the amount of iron stored in the body) are usually elevated in individuals with hemochromatosis. 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 microsomal antibody) are elevated in individuals with autoimmune hepatitis.

Liver ultrasound and CT 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. These tests also can provide important visual information about the liver such as size, contour, scarring, and anatomically important data. A CT liver scan is very useful to detect traumatic injuries to the liver.

A liver biopsy can occasionally assist in determining the cause of liver disease. In this procedure, 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. A liver biopsy is oftentimes performed after an 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. The effectiveness of a certain treatment requires close monitoring at the tissue level
4. No obvious cause of elevated liver tests has been found despite a thorough investigation

Liver biopsy is most useful in confirming a diagnosis of a potentially treatable condition including chronic hepatitis B and C, hemochromatosis, Wilson's disease, autoimmune hepatitis, and alpha-1-antitrypsin deficiency.

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 a lowering of liver enzyme levels to normal or near-normal levels.
• Those who develop a relapse of hepatitis C after completion of treatment will usually develop abnormal liver enzyme levels again.

If you don't have other medical problems, your doctor may suggest lifestyle changes to improve liver function. Severe liver damage is not reversible. You can make a difference if you identify excess fat deposits early.

• Lose weight. If you have extra weight all over, you're more likely to have fat on your liver. Weight loss reduces fat everywhere, including your liver. It's important to pursue healthy weight loss. Don't crash diet to improve liver health.
• Eat healthy. A great place to start is to cut back on how much you eat. Focus on prioritizing healthy foods like fruits, vegetables, lean meat, and whole grains. Eating too much fatty food can still impact your liver even if you're eating less than before. You should also drink plenty of water each day to stay hydrated.
• Lower bad cholesterol levels. There are good fats and bad fats. If your diet is high in saturated and trans-fats, you may have more fat in your blood. This fat can be deposited into your liver when your liver filters blood after digestion.
  • Trade out bad fats for monounsaturated and polyunsaturated fats. Sources of healthy fats include:
    • Olive and other vegetable oils
    • Nuts and seeds
    • Fish
    • Avocado
• Stop drinking alcohol. Your liver is designed to process toxins. But alcohol damages your liver's enzymes. Over time, drinking too much alcohol can lead to permanent damage and cirrhosis. Your liver begins to heal within a few days or weeks of stopping drinking. For severe damage, healing may take several months.
• Exercise regularly. Exercise burns calories. When you eat a healthy diet to lose weight, your body begins to burn the excess stored fat you have. Aim to be active for 30 minutes or more each day. If 30 minutes is too much at once, break your activity down into three 10-minute activity sessions. Build up your endurance over time.
• Manage diabetes. Some health conditions such as diabetes may contribute to liver damage. By controlling your other health conditions, you can improve your liver health. Talk to your doctor and follow any diet, exercise, and weight loss recommendations. Take medications as prescribed and ask your doctor before you stop taking anything.

Aside from AST and ALT, other enzymes including alkaline phosphatase, 5'-nucleotidase ("5 prime" nucleotidase), lactate dehydrogenase (LDH), and gamma-glutamyl transpeptidase (GGT) are often used to detect liver disease.

• LDH is not specific to the liver and can be elevated in many diseases with inflammation in other tissues.
• Alkaline phosphatase is another liver enzyme that is frequently measured. This enzyme is usually found in the walls of the bile ducts (tube-like structures within the liver that connect liver cells). Elevation of alkaline phosphatase may indicate an injury to the biliary cells.
  • Common causes of biliary injury or biliary obstruction (cholestasis) are gallstones and certain medications, although, some of the conditions listed previously can also raise the levels of this enzyme.
• Alkaline phosphate is also found in the bone and 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.