Articles on Medical Diseases and Conditions

Tag: AST

  • Aspartate Aminotransferase (AST)

    Certain enzymes are present in cardiac muscle that are released when tissue necrosis occurs. Serum aspartate aminotransferase (AST, formerly oxaloacetic transaminase, or SGOT) is elevated at some time in 90%-95% of acute MI patients (literature range, 87%-97%). These statistics for sensitivity of the AST in acute MI are based on multiple sequential AST determinations and are therefore not valid for any single determination. Aspartate transaminase levels become elevated 8-12 hours after infarction, reach a peak 24-48 hours after infarction, and fall to normal within 3-8 days. The AST blood levels correlate very roughly with the extent of infarct and may be only transiently and minimally abnormal.

    Besides myocardial injury, the AST level may become elevated because of acute damage to parenchymal cells of the liver, skeletal muscle, kidney, and pancreas. Abnormality due to liver cell injury is especially common (e.g., liver congestion, active cirrhosis, and acute or chronic hepatitis), but an increased AST level will occur with sufficient degrees of skeletal muscle injury (including trauma or extensive surgical damage) and is also found fairly frequently in acute pancreatitis. In some of these situations, myocardial infarct may have to be considered in the differential diagnosis of the patient’s symptoms. Chronic hypokalemia may elevate both AST and also creatine kinase (CK) levels; morphine and meperidine (Demerol) may temporarily raise AST levels, and AST elevations have been reported in occasional patients receiving warfarin sodium (Coumadin) anticoagulant therapy and in some patients taking large doses of salicylates.

    The major drawbacks of the AST in diagnosis of acute MI are the many conditions (especially liver congestion) that can produce AST elevation.

  • Comments on Selection of Liver Function Tests

    A few comments on the use of liver function tests are indicated. It is not necessary to order every test available and keep repeating them all, even those that give essentially the same information. For example, the ALT is sometimes useful in addition to the AST either to establish the origin of an increased AST value (because ALT is more specific for liver disease) or to obtain the AST/ALT ratio when this ratio might be helpful. However, once the results are available, it is rarely necessary to repeat the ALT because it ordinarily does not provide additional assistance to the AST in following the course of the patient’s illness, nor will repetition add much additional useful information to assist diagnosis. The same is true of an elevated ALP level and the use of ALP test substitutes that are more specific for liver disease (gamma glutamyl transferase [GGT]; 5-nucleotidase [5-NT];). Whichever additional enzyme of this group is used, a normal result suggests that bone rather than liver is the source of the increased ALP level and the ALP level alone can be followed without repeating the other enzyme. If the AST level is moderately or markedly elevated and there are obvious signs of liver disease such as jaundice, it would be useless to assay GGT or 5-NT even once for this purpose, since both of them are likely to be elevated regardless of the cause of the liver disease and regardless of bone contribution to ALP. Therefore, rather than enzyme differentiation, many prefer ALP isoenzyme fractionation, which has the added benefit that concurrent elevation of both bone and liver fractions can be demonstrated. For this purpose, ALP isoenzyme electrophoresis is more reliable.

    Aminotransferases of Liver Origin Elevated Over 6 Months Duration
    Chronic active hepatitis virus hepatitis
    Fatty liver (hepatic steatosis)
    Wilson’s disease
    Hemochromatosis
    Alpha-1 antitrypsin deficiency
    Drug-induced
    Alcohol-associated (“active cirrhosis”)
    Primary biliary cirrhosis
    Autoimmune chronic active hepatitis

    Isolated Elevation of Alkaline Phosphatase
    ALP level increased
    AST level normal
    Total bilirubin level normal
    Liver space-occupying lesions
    Bone osteoblastic activity increased
    Drug-induced (dilantin most common)
    Intrahepatic cholestatic process in advanced stage of resolution
    Pregnancy (third trimester)
    Hyperthyroidism
    Hyperparathyroidism

    Serum cholesterol determination is not a very helpful liver function test, although a very high cholesterol level might add a little additional weight to the diagnosis of extrahepatic biliary tract obstruction or biliary cirrhosis. A urine bilirubin determination (“bile”) is not necessary if the serum conjugated bilirubin value is known. Serum protein electrophoresis may help to suggest cirrhosis, but it is not a sensitive screening test, and the pattern most suggestive of cirrhosis is not frequent. The PT as a liver function test is useful only in two situations: (1) an elevated PT not corrected by parenteral vitamin K suggests far-advanced liver destruction, and (2) an elevated PT that is corrected by vitamin K is some evidence for long-standing extrahepatic obstruction in a patient with jaundice. If all test results are normal and inactive cirrhosis is suspected, serum bile acid assay might be useful. The most frequent use for liver scan is to demonstrate metastatic carcinoma to the liver. Ultrasound (or CT scan)—and, in some cases, percutaneous transhepatic cholangiography—are helpful in differentiating extrahepatic from intrahepatic biliary tract obstruction. Liver biopsy can frequently provide a definitive diagnosis, thereby shortening the patient’s stay in the hospital and making lengthy repetition of laboratory tests or other procedures unnecessary. The earlier a biopsy is obtained, the more chance one has to see clear-cut diagnostic changes.

    An initial liver test “profile” might include serum bilirubin, AST, and ALP determinations. If the serum bilirubin level is elevated, it could be separated into conjugated and unconjugated fractions. If the serum bilirubin level is not elevated, determining the GGT may be useful, both to help confirm liver origin for other test abnormalities or to suggest alcoholism if it is elevated out of proportion to the other tests. The PT may be useful if other tests are abnormal to provide a rough idea of the severity of disease. In some cases the results of the initial screening tests permit one to proceed immediately to diagnostic procedures. An AST value more than 20 times normal suggests hepatitis virus hepatitis, and specimens can be obtained for serologic tests diagnostic of acute hepatitis A, B, or C infection (e.g., hepatitis B surface antigen, hepatitis B core antibody-IgM, hepatitis A-IgM, hepatitis C antibody; see Chapter 17). A high bilirubin level or other evidence suggesting biliary tract obstruction can be investigated with biliary tract ultrasound or similar studies. A normal bilirubin level with significantly elevated ALP level not due to bone disease raises the question of metastatic tumor and may warrant a liver scan. If liver screening test results are abnormal but do not point toward any single diagnosis, a liver biopsy might be considered. Liver function tests could be repeated in 2-3 days to see if a significant change takes place, but frequent repetition of the tests and long delays usually do not provide much help in establishing a diagnosis. Also, there are a significant number of exceptions to any of the so-called diagnostic or typical liver function test patterns.

  • Laboratory Test Patterns in Liver Disease

    This section will review several typical patterns of laboratory values found in liver disease, with their differential diagnosis:

    1. An AST value greater than 20 times the upper reference limit.

    If the AST increase is due to liver disease rather than heart or skeletal muscle injury, this suggests acute hepatitis virus hepatitis. Less common etiologies are severe liver passive congestion, active cirrhosis, drug-related liver injury (e.g., acetaminophen), and occasionally atypical early extrahepatic bile duct obstruction. If the ALT level is considerably less elevated than the AST level, this suggests the cause is not hepatitis virus hepatitis. A considerably elevated GGT also would be unusual for hepatitis virus hepatitis A or B and would raise the question of alcohol-related active cirrhosis or early common bile duct obstruction.

    2. An ALP value elevated more than 4 times the upper limit; AST value elevated less than 10 times the upper limit.

    If the ALP is derived from liver rather than bone, this suggests extrahepatic biliary tract obstruction. Serum bilirubin level would be expected to be more than 5 mg/100 ml. Other possible causes are cholestatic drug jaundice, liver space-occupying lesions, primary biliary cirrhosis or primary sclerosing cholangitis, and occasional cases of intrahepatic obstruction of various etiologies.

    3. An ALP value elevated less than 3 times the upper limit; AST value elevated less than 10 times the upper limit.

    This pattern is the most common one seen in patients with liver disease and can be associated with a wide variety of etiologies, including subsiding hepatitis virus hepatitis, chronic hepatitis, infectious mononucleosis, active cirrhosis, alcohol or drug-induced liver injury or dysfunction, acute cholecystitis, acute pancreatitis, severe fatty liver, primary biliary cirrhosis, sepsis, and liver space-occupying lesions. If the AST or ALT level is significantly elevated longer than 6 months, chronic hepatitis virus hepatitis and certain other conditions (see the box) would have to be considered.

    4. An ALP value elevated; AST value not elevated.

    If the ALP elevation is due to liver rather than bone and if other nonhepatic causes (such as phenytoin therapy) for the elevated ALP value can be eliminated, this suggests a space-occupying lesion or lesions in the liver. Other possibilities are primary biliary cirrhosis and resolving phase of previous active liver disease.

  • Serum Aspartate Aminotransferase (AST)

    Serum aspartate aminotransferase (AST; formerly SGOT) is an enzyme found in several organs and tissues, including liver, heart, skeletal muscle, and RBCs. AST elevation from nonhepatic sources is discussed elsewhere.

    AST elevation originating from the liver is due to some degree of acute liver cell injury. Following onset of acute hepatocellular damage from any etiology, AST is released from damaged cells. The serum level becomes elevated in approximately 8 hours, reaches a peak in 24-36 hours, and returns to normal in 3-6 days if the episode is short lived. In mild injury, serum levels may be only transiently and minimally elevated or may even remain within reference limits. In acute hepatitis virus, AST levels frequently become elevated more than 10 times the upper reference range limit (about 75% of patients in one study and 100% in another) and typically rise more than 20 times the upper limit (about 45% of patients in the first study and 90% in the second). In fact, a serum AST more than 20 times normal usually includes acute hepatitis virus infection in the differential diagnosis. However, 1-2 weeks later the values fall toward normal, so that a test sample drawn in the subsiding phase may show moderate or possibly only mild abnormality. In extrahepatic obstruction there usually is no elevation unless secondary parenchymal acute damage is present; when elevations occur, they are usually only mild to moderate (<10 times the upper reference limit). However, when extrahepatic obstruction occurs acutely, AST values may quickly rise to values more than 10 times normal, then fall swiftly after about 72 hours. In cirrhosis, whether the AST level is abnormal and (if abnormal) the degree of abnormality seems to depend on the degree of active hepatic cell injury taking place. Inactive cirrhosis usually is associated with normal AST levels. In active alcoholic cirrhosis, AST elevation is most often mild to moderate, with the majority of AST values less than 5 times the upper range limit and over 95% of AST values less than 10 times normal. In active chronic hepatitis virus hepatitis, AST values are also usually less than 10 times normal. However, one group reported that about 15% of their patients had at some time values more than 10 times normal. However, some of these patients could have superimposed acute infection by non-A, non-B or delta hepatitis virus. In liver passive congestion, AST levels are elevated in 5%-33% of patients. About 80% of these patients have AST elevations less than 3 times normal. In severe acute congestive failure, liver hypoxia may be severe, and one study estimated that about 50% of these patients have AST elevation. In some of these patients AST levels may be higher than 3 times normal and occasionally may even exceed 20 times normal (about 1% of patients with substantial degrees of congestive failure). In some cases AST elevation due to acute myocardial infarction adds to AST arising from the liver. In infectious mononucleosis, AST levels are elevated in 88%-95% of patients, but only about 5% of elevations are greater than 10 times normal and about 2% are more than 20 times normal.

    Some Etiologies for Aspartate Aminotransferase Elevation
    Heart
    Acute myocardial infarct
    Pericarditis (active: some cases)
    Liver
    Hepatitis virus, Epstein-Barr, or cytomegalovirus infection
    Active cirrhosis
    Liver passive congestion or hypoxia
    Alcohol or drug-induced liver dysfunction
    Space-occupying lesions (active)
    Fatty liver (severe)
    Extrahepatic biliary obstruction (early)
    Drug-induced
    Skeletal Muscle
    Acute skeletal muscle injury
    Muscle inflammation (infectious or noninfectious)
    Muscular dystrophy (active)
    Recent surgery
    Delirium tremens
    Kidney
    Acute injury or damage
    Renal infarct
    Other
    Intestinal infarction
    Shock
    Cholecystitis
    Acute pancreatitis
    Hypothyroidism
    Heparin therapy (60%-80% of cases)

    There is a large group of common diseases with mild or moderate AST elevation (defined arbitrarily as elevated less than 10 times the upper reference limit); these include acute hepatitis in the subsiding or recovery phases, chronic hepatitis, active cirrhosis or alcoholic liver disease, liver passive congestion, drug-induced liver dysfunction (including intravenous [IV] or subcutaneous heparin), metastatic liver tumor, long-standing extrahepatic bile duct obstruction, infectious mononucleosis, cytomegalovirus (88%-95%; 2% more than 10 times normal), and fatty liver (40%; rare > 5 x normal). As mentioned earlier, in a few patients with active cirrhosis, liver congestion, infectious mononucleosis, and drug-induced liver injury, the AST may attain levels more than 20 times upper reference limit that are suggestive of acute hepatitis virus infection. AST levels are elevated in approximately 50% of patients with liver metastases, with most elevations less than 5 times the upper reference limit. One report found that obese patients had upper reference limits up to 50% higher than normal-weight persons.

    In active alcoholic cirrhosis, liver congestion, and metastatic tumor to the liver, the AST level usually is considerably higher than the alanine aminotransferase (ALT; formerly SGPT) level, with an AST/ALT ratio greater than 1.0. Ratios less than 1.0 (ALT equal to or greater than AST) are the typical finding in acute hepatitis virus hepatitis and infectious mononucleosis. However, about 30% of patients with acute hepatitis virus infection and some patients with infectious mononucleosis have a ratio greater than 1.0; and ratios either greater than or less than 1.0 may occur in patients with AST elevation due to extrahepatic obstruction. The ratio tends to be more variable and less helpful when the AST value is greater than 10 times the upper reference limit. Some prefer to use an AST/ALT ratio of 1.5 or 2.0 rather than 1.0 as the cutoff point (i.e., an AST value more than twice the ALT value is more suggestive of alcoholic active cirrhosis than hepatitis virus hepatitis, especially if the AST value is less than 10 times normal). Although most agree that active alcoholic liver disease usually yields AST values significantly higher than ALT, there is disagreement in the literature on the usefulness of the ratio (especially the 1.0 value) for diagnosis of individual patients.