SCREENING TESTS OF HEPATOBILIARY DISEASE



Screening tests of hepatobiliary disease, which are listed in Table 43-2, are conveniently divided into two categories: (1) tests of biliary obstruction, and (2) tests of hepatocellular damage, based on the mechanisms responsible for the abnormal test. However, none of the tests is specific for either category, and it is the pattern and magnitude of abnormalities that often provide diagnostic clues to the type of liver disease present.

The serum bilirubin level is the result of bili­rubin production, bilirubin conjugation, and ex­cretion of bilirubin into bile. Its bright orange color made it the first, and the most striking, of liver tests. However, the differential diagnosis of hyperbilirubinemia is extensive (see Chapter 36E) and includes hematologic disorders, congenital abnormalities of bilirubin metabolism, and a wide array of liver diseases. It is nonspecific and only moderately sensitive as a test of liver function. Striking elevations of serum bilirubin, however, should prompt a search for potentially treatable biliary obstruction. Serum bilirubin levels may not return promptly to normal after relief of bil­iary obstruction or improvement in liver disease, because some bilirubin binds covalently to al­bumin and is removed from the circulation only as albumin is catabolized (half-life 14 to 20 days). Serum alkaline phosphatase activity reflects a group of isoenzymes derived from liver, bone, in­testine, and placenta. Serum levels are elevated in association with cholestasis, partial or com­plete bile duct obstruction, and bone regenera­tion, and also with neoplastic, infiltrative, and granulomatous liver diseases. An isolated ele­vated alkaline phosphatase level may be the only clue to partial obstruction of the common bile duct, to obstruction of ducts in a single lobe or segment of liver, or to neoplastic or granuloma­tous disease. Alkaline phosphatase is located on the plasma membrane of hepatocytes. Bile duct obstruction, accompanied by increased serum and tissue levels of bile acids, results in solubilization into the blood stream of bits of hepatocyte mem­brane containing alkaline phosphatase. Increased hepatic bile acid levels also stimulate synthesis of alkaline phosphatase, contributing to the ele­vation of serum levels. 5′-Nucleotidase and gamma glutamyl transpeptidase are other hepa­tocyte plasma membrane enzymes that are simi­larly released into the circulation during bile duct obstruction or cholestasis.

Aspartate [AST] and alanine [ALT] amino­transferases are intracellular ammotransferring enzymes present in large quantities in liver cells. Following injury or death of liver cells, they are released into the circulation. In general, the serum transaminases are sensitive (albeit nonspecific] tests of liver damage, and the height of the serum transaminase activity reflects the severity of he­patic necrosis, but there are important exceptions. Both enzymes require pyridoxal 5-phosphate as a cofactor, and the relatively low serum transami­nase values seen in patients with severe alcoholic hepatitis (often <300 IU/L) may reflect deficiency of this cofactor. Although transaminase levels are increased in a wide array of liver diseases, high levels (>15 times the upper limit of normal) are rare in bile duct obstruction and almost always indicate acute hepatocellular necrosis (e.g., viral or toxic hepatitis).
The commonly available liver tests usually do not indicate the nature of the underlying liver dis­ease; however, the pattern of liver test abnormal­ities may provide insight in this regard. Table 43-3 outlines the most common patterns of liver test abnormalities.