ABSTRACT
As the liver is the major site for drug metabolism, it is not surprising that drug toxicity and
adverse drug reactions would incite variable functional, histological, and ultrastructural
hepatic abnormalities (1-14). Up to 10% of patients with abnormal liver tests are found to
have drug-or toxin-induced hepatic injury, with the incidence rising to over 40% in patients
over the age of 50 (15). Drug-induced liver injury is estimated to occur in up to 1.4% of all
hospitalized patients and in from 2% to 5% of hospitalized patients with jaundice, and is
responsible for up to 15% to 20% of cases of intrahepatic cholestasis. In addition, up to one-half
of all cases of acute liver failure and 20% to 50% of cases of nonviral chronic hepatitis are
associated with drug-induced liver damage (11,12,16-22). The type of liver cell injury may be
intrinsic and dose dependent, whereby the mechanism may relate either to the formation of free
radicals or electrophilic intermediates, or to the production of active oxygen species, which, like
free radicals, lead to lipid peroxidation and direct distortion and destruction of liver cell
membranes (9,23-29). On the other hand, liver cell damage may be idiosyncratic and dose
independent, i.e., dependent on host susceptibility, and may be either immunologically or
metabolically mediated, with inflammatory mediators playing a role (12,16,28,30-33). A wide
variety of hepatic histological changes have been documented as secondary to drugs and toxins
(Table 1) (28,34,35); in addition, up to 1000 drugs and toxins have been implicated in causing
these histological changes (36,37). Even herbal medicines are now increasingly recognized as a
cause of liver injury (38). Although the morphological features are usually reversible with
discontinuation of the medication and toxin exposure, unfortunately, in severe (fulminant)
hepatitis and certain forms of chronic hepatitis, discontinuance of the drug does not alleviate
the sometimes drastic outcomes. This chapter divides drugs and toxins into the various
histological features seen on biopsy.
