Introduction

Drug-induced liver disease has been regarded as rare in children. Large surveys 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 preschool children and in children of any age with cancer. A study examining deaths from adverse drug reactions in children found that approximately one-sixth of such deaths involved acute liver failure, usually associated with antiepileptic or antineoplastic drugs [1]. Drug hepatotoxicity is recognized as an important cause of acute liver failure in children, as in adults [2]. Why childhood drug hepatotoxicity is otherwise relatively uncommon remains unclear. Failure to diagnose and report drug hepatotoxicity in children is a likely explanation. However, most children take relatively few medications. Recent reports of drugs most frequently causing clinically evident hepatotoxicity in adults show that a drug has to be in broad general use to end up a major offender. Although trends may change, children uncommonly take the cardiovascular, antihypertensive, or antidepressant medications commonly associated with hepatotoxicity in adults. Despite increasing prevalence of childhood overweight/obesity, most children have a lean body mass and most do not abuse ethanol or smoke cigarettes. Therefore, children are usually free of 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. Capacity for hepatocellular regeneration may be greater in children than in adults. Nevertheless, drug hepatotoxicity definitely occurs in children; adolescents are probably no different from adults in their risk for drug-induced liver disease.