Liver enzymes and drug-induced hepatotoxicity

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" Although liver markers are not ideal, they still have a vital role in

assessing hepatic function and damage. They are relatively inexpensive

to perform, minimally invasive and readily accessible in a timely

manner. These tests can differentiate the basic sites of liver

compromise, such as the differentiation of hepatocellular from

cholestatic injury, and also give a quantitative assessment of the

degree of impairment. For hepatocellular injury, aspartate

aminotransferase (AST) and alanine aminotransferase (ALT) are generally

increased to values that are 10- to >500-fold of normal. Serum ALP and

gamma glutamyl transpeptidase (GGT) are generally not elevated to any

great extent (i.e., less than three times normal). Many drugs can

produce elevations of aminotransferase enzymes that are up to five times

above the normal range, yet have a very low likelihood of causing

clinical liver damage. For example, heparin can cause transient minor

increases in AST and ALT. In general, continuing treatment for many

drugs is justified if the ALT elevation is less than twice the upper

limit of normal. The key markers of cholestasis are the ALP enzyme, GGT

and bilirubin. "

Source:

http://www.pharmacyconnects.com/content/phpractice/1999/11-99/ce-11-99.html

" As a general principle monitoring is recommended for drugs with

metabolic idiosyncratic hepatotoxic potential - usually, monthly, with

the recommendation to follow ALT elevations <3X upper limit of normal

weekly and with discontinuation of the drug when ALT exceeds 3X upper

limit of normal (with some examples it may be possible to use 5X upper

limit as a cutoff point, but this should be done with great care).

Obviously, since far more patients will develop ALT elevations of a

transient nature than will develop overt liver disease (defined as

jaundice), one will be withholding drugs more often than needed.

Nevertheless, this is a prudent approach considering the inability to

predict precisely which individuals are at risk for a severe reaction

and the dire consequences of overt liver disease. "

Source:

http://www.livertransplant.org/livernewsletter-drug-inducedliverdisease.html

" Special Considerations in Interpreting Liver Function Tests " :

http://www.aafp.org/afp/990415ap/2223.html

" Abnormal findings on liver function tests: Interpreting results to

narrow the diagnosis and establish a prognosis " :

http://www.postgradmed.com/issues/2000/02_00/gopal.htm