Abnormal Liver Function Tests:

Serum levels of aspartate aminotransferase and alanine aminotransferase that exceed 1000 IU/L indicate acute viral hepatitis (A, B and, rarely, C), acute drug toxicity (eg, acetaminophen overdose or isoniazid hepatotoxicity), or ischemic liver injury. In chronic hepatitis (ie, hepatitis B or C or autoimmune), values range from mildly elevated to usually less than 400 IU/L. Elevated levels of alkaline phosphatase and gamma;-glutamyltransferase (GGT) are consistent with cholestatic disease: primary biliary cirrhosis, primary sclerosing cholangitis, idiosyncratic drug reactions, or mechanical biliary obstruction (eg, biliary stones or tumor). Elevation in the GGT level can also be induced by alcohol consumption or medications (eg, phenytoin). Isolated unconjugated hyperbilirubinemia suggests Gilbert syndrome or a hematologic disorder; conjugated hyperbilirubinemia reflects impaired hepatic excretion. Serum bilirubin and albumin and INR have prognostic significance in chronic liver disease; bilirubin and INR are more useful in acute liver failure because albumin has a long half-life. Serum or plasma biochemical tests are widely available, convenient, and sensitive tools for the detection, diagnosis, and monitoring of liver disease. Proper interpretation of these tests involves consideration of the clinical context (patient history, physical examination results, concurrent medical conditions, and medication use), the pattern of liver enzymes and their evolution over time, and the use of additional diagnostic tests. Liver biochemical tests can be divided into 4 categories: Hepatocellular enzymes (serum aminotransferases). Markers of cholestasis (alkaline phosphatase [ALP], gamma;-glutamyltransferase [GGT], 5′ nucleotidase). Tests of liver excretion (bilirubin). Tests of liver synthetic function (albumin, INR). A pattern may emerge in which the elevation of levels of one group of enzymes predominates, suggesting hepatocellular or cholestatic liver injury (Table 1). Often, however, levels of hepatocellular and cholestatic enzymes increase simultaneously and a mixed pattern appears-in which case, the differential diagnosis remains broad and both hepatocellular and hepatobiliary diseases must be considered. Here I provide an overview to help you determine which tests to order, how to interpret the results, and how (and when) to proceed with additional diagnostic testing. HEPATOCELLULAR ENZYMES The aminotransferases are normally present within liver parenchymal cells (hepatocytes) and enter the systemic circulation after injury to the hepatocyte. The serum aminotransferases, or transaminases, of clinical value are aspartate aminotransferase (AST) and alanine aminotransferase (ALT). Although levels of these 2 enzymes are often elevated together, they are not interchangeable, and measuring both is more informative than measuring only one. ALT is regarded as more specific to the liver, since AST is also present in skeletal and cardiac muscle and is elevated in cases of muscle injury or inflammation. The finding of an elevated level of muscle enzyme, such as creatine kinase, distinguishes between diseases of skeletal or cardiac muscle and those of the liver. In many acute and chronic inflammatory liver diseases, ALT values tend to be higher than AST values. An often-cited exception is alcoholic hepatitis, in which the AST:ALT ratio is typically greater than 2. This is attributed to the effects of long-term alcohol use on intracellular aminotransferase levels; it also reflects alcohol-mediated mitochondrial injury (AST is present in mitochondria and cytosol, whereas ALT is only cytosolic). The magnitude and evolution of AST and ALT can provide useful clues to the nature of the underlying liver disease (Case I). Aminotransferase values greater than 1000 IU/L reflect significant hepatocyte