ABSTRACT
Hepatotoxic adverse drug reactions have contributed to the decline of many promising
therapies, even among mainstream medication classes (bromfenac and troglitazone are
recent examples). The spectrum of nonsteroidal anti-inflammatory drug-related liver
toxicity continues to expand, with reports in children, interactive toxicity in persons
with hepatitis C, and recognition of the toxicity of both the preferential and selective
cyclooxygenase-2 inhibitors. Of the antihypertensive agents, methyldopa is now rarely
prescribed and adverse effects are reported infrequently, whereas cases of liver injury
associated with the angiotensin receptor and converting enzyme inhibitors are increasingly
reported. Of the antidiabetic agents, acarbose, gliclazide, metformin, and human insulin
have been implicated in causing liver injury. To date, the newer thiazolidinediones
do not appear to share the hepatotoxic potential of troglitazone, although a few reports
of acute hepatitis have accrued. Although liver injury has been associated with the
``statins,'' the frequency of such toxicity is lower than that of the background population
and the value of biochemical monitoring remains unproved. Newer concepts in anticonvulsant
hepatotoxicity have been the recognition of the reactive metabolite syndrome, delineation
of the risk factors for valproic acid toxicity, the potential role of carnitine in
preventing valproic acid hepatotoxicity, and the toxicity of second-line antiepileptic
drugs. Liver injury associated with newer psychotropic agents, particularly the selective
serotonin reuptake inhibitors, is also discussed. The focus of the review is the hepatotoxicity
of commonly used drugs with particular reference to recent and novel reports of toxicity.
Well-known causes of liver injury such as chlorpromazine, phenytoin, and methyldopa
are not discussed.
KEYWORDS
Hepatotoxicity - drug-induced liver disease - liver injury - cholestasis - fulminant
hepatic failure - antihypertensive drugs - antidiabetic agents - nonsteroidal anti-inflammatory
drugs - psychotropic agents