High levels of GGT and AP hint at a possible blockage of the bile ducts, or of possible injury to, or inflammation of, the bile ducts. This type of problem is characterized by an impairment, or failure, of bile flow, which is known as cholestasis. This type of liver injury is known as cholestatic liver injury, and this type of liver disease is known as cholestatic liver disease. (Primary biliary cirrhosis, discussed in Chapter 15, is an example of a cholestatic liver disease.) Intrahepatic cholestasis refers to bile duct blockage or injury within the liver. Intrahepatic cholestasis may occur in people with primary biliary cirrhosis or liver cancer (see Chapter 19), for example. Extrahepatic cholestasis refers to bile duct blockage or injury occurring outside the liver. Extra­hepatic cholestasis may occur in people with gallstones. When a blockage or inflammation of the bile ducts occurs, the GGT and AP can overflow like a backed up sewer and seep out of the liver and into the bloodstream. These enzymes typically become markedly elevated—approximately ten times the upper limit of normal. GGT is found predominantly in the liver. AP is mainly found in the bones and the liver but can also be found in many other organs, such as the intestines, kidneys, and placenta. Therefore, elevated levels of AP will indicate that something is wrong with the liver only if the amount of GGT is raised as well. Keep in mind that, GGT can be elevated without AP being elevated, as GGT is a sensitive marker of alcohol ingestion and certain hepatotoxic (liver toxic) drugs. It should be noted that for unclear reasons, people who smoke cigarettes appear to have higher AP and GGT than nonsmokers. Also, levels of AP and GGT are most accurate after a twelve-hour fast. You are beginning to get an inkling of the complexities that arise when evaluating abnormal LFTs!