Elevation of liver-derived alkaline phosphatase is not totally specific for cholestasis, and a less than threefold elevation can be seen in almost any type of liver disease. Alkaline phosphatase elevations greater than four times normal occur primarily in patients with cholestatic liver disorders, infiltrative liver diseases such as cancer and amyloidosis, and bone conditions characterized by rapid bone turnover (e.g., Paget’s disease). In bone diseases, the elevation is due to increased amounts of the bone isoenzymes. In liver diseases, the elevation is almost always due to increased amounts of the liver isoenzyme. If an elevated serum alkaline phosphatase is the only abnormal finding in an apparently healthy person, or if the degree of elevation is higher than expected in the clinical setting, identification of the source of elevated isoenzymes is helpful (Fig. 330-1). This problem can be approached in two ways. First, and most precise, is the fractionation of the alkaline phosphatase by electrophoresis. The second, best sub- stantiated, and most available approach involves the measurement of serum 5′-nucleotidase or GGT. These enzymes are rarely elevated in conditions other than liver disease.