The severity of hepatic damage is usually dose-related but when due to a drug metabolite rather than the parent drug, such as paracetamol, toxicity may relate to the rate of metabolite formation. Enzyme inducing agents such as alcohol or anticonvulsants may potentiate biotransformation and consequent hepatotoxicity. In idiosyncratic drug- induced liver disease, a harmful effect on liver structure and function is seen in only a small percentage of patients treated with the responsible agent. There is usually no relationship between the magnitude of the dose or the duration of therapy and the onset or severity of liver damage. Drug-induced liver disease occurs in all races and both sexes.
Age distribution is considered to be bimodal with peaks in the twenties and sixties.
Unfortunately, the diagnosis of drug-induced liver disease is often missed. The combination of fever, jaundice, rash, adenopathy, tender liver, eosinophilia and raised transaminases associated with the recent introduction of a single therapeutic agent represents a caricature which is rarely seen in practice. Although clinical and biochemical data are often unhelpful, the absence of fever and usual gastrointestinal symptoms in a patient with hepatitis should alert the clinician to the possibility that the illness may be drug-induced. Features strengthening the diagnosis are a satisfactory response to withdrawal of the agent and negative serology for hepatitis viruses. Rechallenge may be diagnostic but deliberate re-exposure of a patient to medication suspected of being hepatotoxic is often dangerous and has resulted in deaths.