Articles on Medical Diseases and Conditions

Tag: Liver Tract Tests

  • Extrahepatic Biliary Tract

    The major subdivisions of the biliary tract are the intrahepatic bile ducts, the common bile duct, and the gallbladder. The major diseases of the extrahepatic biliary system are gallbladder inflammation (cholecystitis, acute or chronic), gallbladder stones, and obstruction to the common bile duct by stones or tumor. Obstruction to intrahepatic bile channels can occur as a result of acute hepatocellular damage, but this aspect was noted in the discussion of liver function tests and will not be repeated here.

    Acute cholecystitis usually presents with upper abdominal pain, most often accompanied by fever and a leukocytosis. Occasionally, difficulty in diagnosis may be produced by a right lower lobe pneumonia or peptic ulcer, and cholecystitis occasionally results in ST and T wave electrocardiographic changes that might point toward myocardial disease. Acute cholecystitis is very frequently associated with gallbladder calculi, and 90%-95% have a stone in the cystic duct. Some degree of increased bilirubin level is found in 25%-30% of patients, with a range in the literature of 6%-50%. Bilirubinemia may occur even in patients without stones. Acute cholecystitis without stones is said to be most common in elderly persons and in patients who are postoperative. AST may be elevated in nearly 75% of acute cholecystitis patients; this is more likely if jaundice is present. In one study, about 20% of patients had AST levels more than 6 times normal, and 5% had levels more than 10 times normal. Of these, some had jaundice and some did not. Alkaline phosphatase levels are elevated in about 30% of patients with acute cholecystitis. Cholecystitis patients sometimes have an elevated serum amylase level, usually less than 2 times normal limits. About 15% of patients are said to have some degree of concurrent acute pancreatitis.

    In our own hospital, of 25 consecutive surgical patients with microscopically proven acute cholecystitis, admission levels of total bilirubin, AST (SGOT), and ALP were all normal in 56% of the patients. Interestingly, all three tests were normal in some patients who had severe tissue abnormality. Total bilirubin, AST, and ALP were all elevated in 12% of the 25 patients. AST was elevated in 36% of the 25 patients, with about half the values less than twice the upper reference range limit and the highest value 7.5 times the upper limit. AST was the only value elevated in 16% of the 25 patients. ALP was elevated in 28% of the 25 patients; the highest value was three times the upper reference limit. The ALP was the only value elevated in 8% of the 25 patients. AST and ALP were elevated with normal total bilirubin in 8% of the 25 patients.

    About 20% of patients with acute cholecystitis are reported to have common duct stones. In one series, about 40% of patients with common duct stones did not become jaundiced, and about 20% had an elevated bilirubin level less than 3 mg/100 ml. Common duct stones usually occur in association with gallbladder calculi but occasionally are present alone. In one study, 17% of patients with common duct stones had a normal ALP level; in 29%, the ALP level was elevated to less than twice normal; 11% had values between two and three times normal; and 42% were more than three times normal.

    In uncomplicated obstructive jaundice due to common duct stones or tumor, AST and LDH values are usually normal. Nevertheless, when acute obstruction occurs, in some instances AST levels may become temporarily elevated very early after the onset of obstruction (sometimes with AST levels more than 10 times normal) in the absence of demonstrable hepatocellular damage. The striking AST elevation may lead to a misdiagnosis of hepatitis. Several reports indicate that LDH levels are also considerably elevated in these patients, usually 5 times the upper limits of normal. Since LDH levels are usually less than twice normal in hepatitis virus hepatitis (although occasional exceptions occur), higher LDH values point toward the “atypical obstruction” enzyme pattern. Both AST and LDH values usually fall steadily after 2-3 days.

    Radiologic procedures

    Diagnosis of stones in the gallbladder or common bile duct rests mainly with the radiologist. On plain films of the abdomen, 20%-25% of gallbladder stones are said to be visible. Oral cholecystography consists of oral administration of a radiopaque contrast medium that is absorbed by intestinal mucosa and secreted by liver cells into the bile. When bile enters the common duct, it takes a certain amount of pressure to force open the ampulla of Vater. During the time this pressure is building up, bile enters the cystic duct into the gallbladder where water is reabsorbed, concentrating the bile. This process allows concentration of the contrast medium as well as the bile and, therefore, outlines the interior of the gallbladder and delineates any stones of sufficient size. An average of 70% of patients with gallbladder calculi may be identified by oral cholecystography. Repeated examination (using a double dose of contrast medium or alternative techniques) is necessary if the original study does not show any gallbladder function. In most of the remaining patients with gallbladder calculi, oral cholecystography reveals a poorly functioning or a nonfunctioning gallbladder. Less than 5% of patients with gallbladder stones are said to have a completely normal oral cholecystogram. (More than 50% of patients with cholecystitis and gallbladder tumor have abnormal oral cholecystograms.)

    There are certain limitations to the oral method. Although false negative examination results (gallbladder calculi and a normal test result) are relatively few, false positive results (nonfunctioning gallbladder but no gallbladder disease) have been reported in some studies in more than 10% of cases. In addition, neither oral cholecystography nor plain films of the abdomen are very useful in detecting stones in the common bile duct. Visualization of the common bile duct by the oral method is frequently poor, whether stones are present or not.

    IV cholecystography supplements the oral procedure in some respects. Nearly 50% of common duct stones may be identified. Intravenous injection of the contrast medium is frequently able to outline the common duct and major intrahepatic bile ducts. However, IV cholecystography is being replaced by other techniques such as ultrasound, because limitations of the IV technique include poor reliability in demonstrating gallbladder calculi (since there are an appreciable number of both false positive and false negative results) and a considerable incidence of patient reaction to the contrast medium (although newer techniques, such as drip infusion, have markedly reduced the danger of reaction).

    A limitation to both the oral and the IV procedure is that both depend on a patent intrahepatic and extrahepatic biliary system. If the serum bilirubin level is more than 2 mg/100 ml (34 µmol/L) (and the increase is not due to hemolytic anemia), neither oral nor IV cholangiography is usually satisfactory.

    Ultrasound is another very useful modality in the diagnosis of cholecystitis. Sensitivity is about the same as that of oral cholecystography (94%-95%; literature range, 89%-96%). However, ultrasound gives fewer false positive results < 5%). Ultrasound visualizes more stones than oral cholecystography, which is an advantage in deciding whether or not to perform surgery. For example, one study showed that ultrasound detected twice as many calculus-containing gallbladders in patients with nonfunctioning gallbladders than oral cholecystography. In addition, ultrasound can be performed the same day that the diagnosis is first suspected and is not affected by some factors that make oral cholecystography difficult or impossible (e.g., a severely ill patient, severe diarrhea or vomiting, jaundice, pregnancy, and sensitivity to x-ray contrast media). Therefore, some physicians use ultrasound as the first or primary procedure in possible cholecystitis. Others perform single-dose oral cholecystography first, and if the gallbladder does not visualize but no stones are found on first examination, ultrasound is performed.

    CT was discussed earlier. It is generally not ordered in acute cholecystitis unless there is suspicion of additional problems in the gallbladder area or in the abdomen.

    Biliary tract radionuclide scanning is becoming available in larger centers using technetium-labeled iminodiacetic acid (IDA) complexes such as diisopropyl-IDA (DISIDA), which are extracted by the liver and excreted in bile. Normally the gallbladder, common bile duct, and isotope within the duodenum can be visualized. In acute cholecystitis there is cystic duct obstruction, and the gallbladder does not visualize on scan. This technique is said to have a sensitivity of 95%-98% with less than 5% false positive results. Many consider it the current procedure of choice in acute cholecystitis. Standard gray-scale ultrasound is not quite as good in detecting acute cholecystitis as it is in detecting chronic cholecystitis, although real-time ultrasound sensitivity is said to be 95% accurate or better. The ability of ultrasound to visualize stones is an advantage, but radionuclide scanning has an advantage in patients with acute acalculous cholecystitis. Radionuclide scan diagnosis of chronic cholecystitis is not nearly as accurate as detection of acute cholecystitis, and the technique usually does not visualize stones. Because the common duct can be visualized even when the serum bilirubin level is elevated, DISIDA scanning can also be useful in early or acute extrahepatic obstruction. In early or acute common duct obstruction the common duct may not yet be sufficiently dilated to produce abnormal ultrasound sonograms or abnormal CT scans. However, in long-standing obstruction, hepatic parenchymal cells are injured and cannot extract the IDA compounds from the blood sufficiently well to consistently fill the common duct. If symptoms persist or if there is a suggestion of complications, DISIDA scanning is useful after biliary tract operations.

    One report indicates a significant number of false positive results (gallbladder nonvisualization) in patients who have alcoholic liver disease and in patients on total parenteral nutrition therapy.

  • Reye’s Syndrome

    Reye’s syndrome usually begins a few days after onset of a viral illness, most often one of the influenza viruses or varicella. The disease predominantly affects children and young adolescents, with a peak incidence between ages 5 and 15 years. Onset of the disease is manifested by symptoms of encephalitis (e.g., confusion, lethargy, or aggressive behavior), without focal neurologic signs, that accompany or follow onset of protracted or recurrent vomiting. Temperature is usually normal. There is laboratory evidence of liver cell injury, with AST or ALT more than 3 times the upper limit of the reference range, with some patients exceeding 20 or even 25 times the upper limit. Serum total bilirubin is usually normal, and clinical jaundice is rare. Nevertheless, the PT is usually elevated, and blood ammonia level is frequently elevated. Routine CSF test results are usually normal. Creatine phosphokinase level is markedly abnormal, and phosphorus level is decreased, indicating muscle involvement. Fatty liver is frequently found on biopsy or autopsy. Although exact etiology is not known, influenza A and B, especially B, have been associated with the majority of cases, with chickenpox next most frequent and other viruses also implicated on occasion. There is also very strong association with aspirin use during a viral infection.

    Conditions that may simulate Reye’s syndrome and that can be ruled out by assay of serum levels or other tests include salicylate or acetaminophen overdose, valproic acid toxicity, encephalitis from other causes (e.g., herpes simplex virus) with superimposed creatine phosphokinase elevation due to intramuscular injection, denatured alcohol poisoning, and acute lead poisoning. Certain rare inborn errors of metabolism (e.g., deficiency of ornithine transcarbamylase) may be manifested by symptoms that suggest Reye’s syndrome.

  • Fatty Liver

    Fatty liver is a common cause of hepatomegaly of unknown etiology. In uncomplicated fatty liver, function tests are variable. There may be no abnormality at all. ALP levels in one series were elevated in nearly 48% of patients but usually were less than twice normal. An elevated AST level is found in 40% of patients, usually less than 5 times normal, and more often with severe degrees of fatty metamorphosis. The serum bilirubin level may be elevated in 35% of patients, but most have minimal abnormality, usually less than twice normal and without jaundice. Severe fatty liver may present clinically with jaundice, but this is very uncommon.

  • Primary Biliary Cirrhosis

    Primary biliary cirrhosis is an uncommon type of biliary obstruction that should be briefly mentioned. It occurs predominantly in young or middle-aged women and typically is a slow process. On liver biopsy there is inflammation and destruction of small bile ducts within liver portal areas. Clinically there is pruritus with or without mild jaundice. Steatorrhea is sometimes present. Biochemically, there usually is an ALP and GGT increase more than 3 times the normal limit, increased serum cholesterol level, and normal or mildly increased AST levels. Serum antimitochondrial antibodies are elevated in 90% or more patients. Diagnosis is made on the basis of the clinical and biochemical pattern plus the presence of antimitochondrial antibodies. Liver biopsy may be necessary to differentiate the disease from chronic hepatitis, liver tumor, drug-induced cholestasis, or some other conditions associated with cholangitis.

  • Biliary Obstruction

    Obstruction may be complete or incomplete, extrahepatic or intrahepatic. Extrahepatic obstruction is most often produced by gallstones in the common bile duct or by carcinoma of the head of the pancreas. Intrahepatic obstruction is most often found in the obstructive phase of acute hepatocellular damage, as seen in “active” alcoholic cirrhosis, hepatitis virus hepatitis, in liver reaction to certain drugs such as chlorpromazine (Thorazine), and occasionally in patients with other conditions such as metastatic carcinoma. In one series, 12% of patients with liver metastases had a total bilirubin level more than 10 mg/100 ml (170 µmol/L). Serum bilirubin levels may become markedly elevated with either intrahepatic or extrahepatic obstruction. Although extrahepatic obstruction typically is associated with considerable bilirubin elevation, bilirubin values may be only mildly elevated in the early phases of obstruction, in persons with incomplete or intermittent obstruction, and in some persons with common duct obstruction by stones. In addition, occasional patients with intrahepatic cholestasis have considerably elevated serum bilirubin levels. Thus, the degree of bilirubinemia is not a completely reliable diagnostic point. Patients with extrahepatic obstruction typically have ALP elevation more than 3 times the upper reference limit, normal or minimally elevated AST levels, and moderately or considerably elevated total bilirubin levels, with 75% or more consisting of the conjugated fraction. In contrast, intrahepatic obstruction due to hepatocellular injury usually is associated with a considerably elevated AST level and a conjugated bilirubin/nonconjugated bilirubin ratio close to 1:1. Unfortunately, as time goes on, the serum bilirubin level in extrahepatic obstruction demonstrates a progressive decline in the conjugated bilirubin/nonconjugated bilirubin ratio, until a ratio not far from 1:1 is reached. Also, the AST level may increase somewhat as liver cells are damaged by distended biliary ductules. Therefore, differentiation of long-standing extrahepatic obstruction from intrahepatic obstruction may not always be easy. Metastatic tumor to the liver has the typical laboratory picture of extrahepatic obstruction without jaundice. Occasionally, however, it is accompanied by jaundice. Finally, some drugs such as chlorpromazine, anabolic steroids, or oral contraceptives may occasionally produce liver dysfunction that has a predominantly cholestatic-type biochemical pattern.

    Some Etiologies for Aspartate Aminotransferase Values Over 1000 IU/ml
    Liver origin
    Acute hepatitis virus hepatitis
    Chronic active hepatitis (occasional patients; 16% in one study)
    Reye’s syndrome
    Severe liver passive congestion or hypoxia (with or without acute MI, shock, or sepsis)
    Drug-induced (e.g., acetaminophen)
    HELLP syndrome of pregnancy (some patients)
    Other
    First 2-3 days of acute common bile duct obstruction
    Acute myocardial infarct (occasional patients)
    Severe rhabdomyolysis

    If extrahepatic obstruction is a possibility, it can be investigated with ultrasound on the biliary tract. If results of the ultrasound study are normal or equivocal and extrahepatic obstruction is strongly suspected, one of the other studies discussed previously can be attempted.

  • Acute Hepatitis Virus Hepatitis

    Hepatitis virus B will be used as a model here. After an incubation period, acute viral hepatitis most often begins with some combination of GI tract symptoms, fever, chills, and malaise, lasting 4-7 days. During this phase there is no clinical jaundice. Leukopenia with a relative lymphocytosis is common, and there may be a few atypical lymphocytes. Hemoglobin values and platelet counts usually are normal. Liver function tests reflect acute hepatocellular damage, with AST and ALT values more than 10 times the upper reference limit and usually more than 20 times the upper limit. ALP is usually elevated; values typically are less than 3 times the upper reference limit, but some patients may have elevation even higher than 5 times the upper limit. Lactic dehydrogenase (LDH) is usually less than 3 times normal. Serum bilirubin values begin climbing toward the end of this initial phase. The next development is visible jaundice; during this period, clinical symptoms tend to subside. The serum bilirubin level continues to rise for a time, then slowly falls. Both conjugated and unconjugated fractions are increased. The ALP level often begins to fall shortly after clinical icterus begins. The AST level begins to decrease about 1-2 weeks after it reaches its peak. A convalescent phase eventually ensues, with return of all test values to normal, beginning with the ALP. Some patients continue to manifest a low-grade hepatitis (chronic persistent or chronic active), reflected by variable and intermittent AST abnormalities (usually mild or moderate in degree) with or without ALP elevation. The majority of patients (75%-80%) never develop jaundice during viral hepatitis; this condition is known as “anicteric hepatitis.” In such situations, function tests reveal mild to moderate acute hepatocellular damage with a minimal obstructive component.

    The textbook picture of AST more than 20 times (especially when over 25 times) the upper reference range limit (see the box), an ALT level greater than or equal to AST; with ALP mildly elevated and GGT mildly or moderately elevated, is strongly suggestive of hepatitis virus hepatitis. Other liver disorders that may be associated with an AST level over 20 times the upper reference limit include a small minority of patients with drug-induced liver injury (especially acetaminophen overdose), active alcoholic cirrhosis, a few cases (2%) of infectious mononucleosis, and some cases of severe liver passive congestion, as well as a few patients with early “atypical” extrahepatic obstruction. In addition, there are nonhepatic etiologies for markedly elevated AST, such as acute myocardial infarct and severe skeletal muscle injury. The patient may not be seen until the early convalescent phase, or the patient may have a mild anicteric episode. If so, the AST level may have decreased to less than 20 times the upper reference limit, and the differential diagnosis includes a wide variety of conditions, such as subsiding hepatitis, chronic hepatitis, alcoholic and active cirrhosis, infectious mononucleosis or cytomegalovirus infection, liver congestion, drug-induced liver dysfunction, liver space-occupying lesions, and severe fatty liver.

    Chronic hepatitis is usually associated with AST values less than 20 times the upper reference limit and usually less than 10 times the upper limit. However, one study reported that about 15% of persons with the category of chronic hepatitis known as “chronic active hepatitis” had AST values at some time greater than 20 times the upper reference limit.

  • Liver Biopsy

    This procedure has been greatly simplified, and its morbidity and mortality markedly reduced, by the introduction of small-caliber biopsy needles such as the Menghini. Nevertheless, there is a small but definite risk. Relative contraindications to biopsy include a PT in the anticoagulant range or a platelet count less than 50,000/mm3. Liver biopsy is especially useful in the following circumstances:

    1. To differentiate among the many etiologies of liver function test abnormality when the clinical picture and laboratory test pattern are not diagnostic. This most often happens when the AST level is less than 10 or 20 times the upper reference limit and the ALP level is less than 3 times the upper limit. In cases of possible obstructive jaundice, extrahepatic obstruction should be ruled out first by some modality such as ultrasound.
    2. To prove the diagnosis of metastatic or primary hepatic carcinoma in a patient who would otherwise be operable or who does not have a known primary lesion (in a patient with an inoperable known primary lesion, such a procedure would be academic).
    3. In hepatomegaly of unknown origin whose etiology cannot be determined otherwise.
    4. In a relatively few selected patients who have systemic diseases affecting the liver, such as miliary tuberculosis, in whom the diagnosis cannot be established by other means.

    A discussion of liver biopsy should be concluded with a few words of caution. Two disadvantages are soon recognized by anyone who deals with a large number of liver specimens. First, the procedure is a needle biopsy, which means that a very small fragment of tissue, often partially destroyed, is taken in a random sample manner from a large organ. Localized disease is easily missed. Detection rate of liver metastases is about 50%-70% with blind biopsy and about 85% (range, 67%-96%) using ultrasound guidance. Second, many diseases produce nonspecific changes that may be spotty, may be healing, or may be minimal. Even with an autopsy specimen it may be difficult to make a definite diagnosis in many situations, including the etiology of many cases of cirrhosis. The pathologist should be supplied with the pertinent history, physical findings, and laboratory data; sometimes these have as much value for interpretation of the microscopic findings as the histologic changes themselves.

    In summary, liver biopsy is often indicated in difficult cases but do not expect it to be infallible or even invariably helpful. The best time for biopsy is as early as possible after onset of symptoms. The longer that biopsy is delayed, the more chance that diagnostic features of the acute phase have disappeared or are obscured by transition to healing.

  • Computerized Tomography and Ultrasound

    Ultrasound has been reported to detect metastatic liver tumor in approximately 85%-90% of patients (literature range, 63%-96%, with some of the lower figures being earlier ones). Computerized tomography (CT) has a sensitivity of 90%-95%. Radionuclide scans detect a few more patients with diffuse liver abnormality than CT or ultrasound. However, CT and ultrasound can differentiate cysts from solid lesions in the liver, which both look the same on radionuclide scanning. CT can also detect abnormalities outside the liver as incidental findings to a liver study. Ribs may interfere with ultrasound examination of the liver dome area, and gas in the hepatic flexure of the colon can interfere in the lower area of the liver. Magnetic resonance imaging (MRI) has about the same detection rate as CT but is much more expensive and at times has some problems with liver motion due to relatively slow scan speed.

    CT and ultrasound are important aids in differentiating extrahepatic from intrahepatic biliary tract obstruction through visualization of the diameter of the intrahepatic and common bile ducts. In complete extrahepatic obstruction, after a few days the common bile duct becomes dilated; in most cases the intrahepatic ducts eventually also become dilated. In intrahepatic obstruction the common bile duct is not dilated. Ultrasound has asensitivity of about 93% (literature range, 77%-100%), and CT is reported to have a sensitivity of about 94% (literature range, 85%-98%). There have also been considerable advances in the ability of ultrasound and CT to demonstrate the approximate location of obstruction in the biliary system as well as making an overall diagnosis of obstruction. Gas in the intestine may interfere with ultrasound in a few cases.

    In general, most investigators believe that ultrasound is the procedure of choice in possible biliary tract obstruction; those few cases that are equivocal or technically inadequate with ultrasound can be studied by CT or some other technique such as percutaneous transhepatic cholangiography.

  • Radionuclide Liver Scan

    If a radioactive colloidal preparation is injected intravenously, it is picked up by the reticuloendothelial system. The Kupffer cells of the liver take up most of the radioactive material in normal circumstances, with a small amount being deposited in the spleen and bone marrow. If a sensitive radioactive counting device is placed over the liver, a two-dimensional image or map can be obtained of the distribution of radioactivity. A similar procedure can be done with thyroid and kidney using radioactive material that these organs normally take up (e.g., iodine in the case of the thyroid). Certain diseases may be suggested on liver scan if the proper circumstances are present:

    1. Space-occupying lesions, such as tumor or abscess, are often visualized as discrete filling defects if they are more than 2 cm in diameter.
    2. Cirrhosis typically has a diffusely nonuniform appearance accompanied by splenomegaly, but the cirrhotic process usually must be well established before scan abnormality (other than hepatomegaly) is seen. The most typical picture is obtained in far-advanced cases, but the scan appearance may differ somewhat even in these patients.
    3. Fatty liver has an isotope distribution like that of cirrhosis, but only if severe.
    4. Liver scanning may be useful to differentiate abdominal masses from an enlarged liver.

    Undoubtedly, more sensitive equipment will become available and, perhaps, better radioactive isotopes. At present, useful as the liver scan may be, it is often difficult to distinguish among cirrhosis, fatty liver, and disseminated metastatic carcinoma with nodules less than 2 cm in diameter. Liver scan is reported to detect metastatic carcinoma in 80%-85% of patients tested (literature range, 57%-97%) and to suggest a false positive diagnosis in 5%-10% of patients without cancer. The majority of these false positive studies are in patients with cirrhosis, hepatic cysts, hemangiomas, or a prominent porta hepatis.

  • Alpha Fetoprotein Test (AFP)

    Fetal liver produces an alpha-1 globulin called “alpha fetoprotein” (AFP), which becomes the dominant fetal serum protein in the first trimester, reaching a peak at 12 weeks, then declining to 1% of the peak at birth. By age 1 year, a much greater decrease has occurred. Primary liver cell carcinomas (hepatomas) were found to produce a similar protein; therefore, a test for hepatoma could be devised using antibodies against AFP antigen. Original techniques, such as immunodiffusion, were relatively insensitive and could not detect normal quantities of AFP in adult serum. Extensive studies using immunodiffusion in several countries revealed that 30%-40% of European hepatoma patients who were white had positive test results, whereas the rate among Chinese and African Americans with hepatoma was 60%-75%. Men seemed to have a higher positive rate than women. Besides hepatoma, embryonal cell carcinoma and teratomas of the testes had an appreciable positivity rate. Reports of false positive results with other conditions included several cases of gastric carcinoma with liver metastases and a few cases of pregnancy in the second trimester. Subsequently, when much more sensitive radioimmunoassay techniques were devised, small quantities of AFP were detected in normal adult individuals. RIA and EIA have increased the abnormality rate in hepatoma somewhat, especially in European patients, whereas elevations accompanying other conditions are also more frequent. For example, according to one report, AFP levels were increased in approximately 75% of hepatoma cases, 75% of embryonal carcinomas or teratomas of the testes, 20% of pancreatic or gastric carcinomas, and 5% of colon and lung carcinomas. Others have found AFP elevations by immunoassay methods in 90% or more of hepatomas (literature range, 69%-100%) and in 0%-5% of various nonneoplastic liver diseases. The most frequent nonneoplastic elevations occurred in conditions associated with active necrosis of liver cells, such as hepatitis and active alcoholic cirrhosis. An AFP level of 500 ng/ml was suggested by several investigators as a cutoff point in differentiating hepatoma from nonneoplastic liver disease. Almost all of the nonneoplastic disease (except some cases of hepatitis virus hepatitis) were less than 500 ng/ml, whereas 50% or more patients with hepatoma had values higher than this.