Drug-induced disorders cholestasis

Alkaline phosphatase levels and GGT are elevated in plasma with obstructive disorders that disrupt the flow of bile from hepatocytes to the bile ducts or from the biliary tree to the intestines in condition such as primary biliary cirrhosis, sclerosing cholangitis, drug-induced cholestasis, gallstone disease, and autoimmune cholestatic liver disease. 

Inflammatory conditions of the liver, in particular inflammatory hepatocellular cholestasis, are one of the most frequent causes of jaundice in the clinic. The major underlying denominator of this disorder is the inhibition of transporter expression and function by proinflammatory cytokines, which are either induced systemically or within the liver. Alcoholic hepatitis accounts for up to two-thirds of patients and is the most frequent trigger, followed by idiosyncratic drug reactions, sepsis or other extrahepatic bacterial infections, some variants of viral hepatitis, and total parenteral nutrition [95, 96]. 

Measurement of serum y-GT activity has clinical significance. The enzyme is present in all tissues, but the highest level is in the kidney however, the serum enzyme originates primarily from the hepatobiliary system. Elevated levels of serum y-GT are found in the following disorders intra- and posthepatic biliary obstruction (elevated serum y-GT indicates cholestasis, as do leucine aminopeptidase, 5 -nucleotidase, and alkaline phosphatase) primary or disseminated neoplasms some pancreatic cancers, especially when associated with hepatobiliary obstruction alcohol-induced liver disease (serum y-GT may be exquisitely sensitive to alcohol-induced liver injury) and some prostatic carcinomas (serum from normal males has 50% higher activity than that of females). Increased activity is also found in patients receiving phenobarbital or phenytoin, possibly due to induction of y-GT in liver cells by these drugs. 

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