20 - Drug-Induced Liver Disease

Summary

Drug-induced liver disease is generally regarded as rare in children. Large inpatient [1] and outpatient surveys [2] have generally failed to detect drug hepatotoxicity as a major problem in children, although adverse drug reactions (not necessarily hepatotoxic) are somewhat more frequent in the under-5-year-old group and in children of any age with cancer. A recent study examined deaths from adverse drug reactions in children and found that approximately one sixth of such deaths involved acute liver failure, usually associated with antiepileptic or antineoplastic drugs [3]. Drug hepatotoxicity is now recognized as an important cause of acute liver failure in children as in adults [4]. Why childhood drug hepatotoxicity is otherwise relatively uncommon is not clear. Failure to diagnose and report drug hepatotoxicity in children is a likely explanation. Another important consideration is that most children take relatively few medications, and in particular they rarely take the cardiovascular, antihypertensive, or antidepressant medications commonly associated with hepatotoxicity in adults. Most children have a lean body mass, and most do not use ethanol chronically or smoke cigarettes. Thus, children are usually free of many of the factors predisposing to drug hepatotoxicity in adults. Hepatic drug metabolism in children may be sufficiently different from that in adults to shield against drug hepatotoxicity. Indeed, old age is a risk factor for more severe hepatotoxic reactions, perhaps because the aging liver metabolizes some drugs more slowly. Adult women are somewhat more prone to certain drug hepatotoxicities than men.