Paracetamol-induced hepatotoxicity at recommended dosage

In patients who develop liver damage following moderate paracetamol overdose in the order of 5-10 g daily, recent fasting and nutritional impairment have been identified as key precipitants. Hepatotoxicity caused by paracetamol at recommended dosage, in the absence of exposure to enzyme-inducing drugs, has recently been described as an idiosyncratic phenomenon. The possible importance of fasting and malnutrition in this setting is uncertain. We report a severely malnourished 53-year-old woman who developed severe hepatotoxicity whilst receiving paracetamol at recommended dosage (4 g daily) following a period of fasting, in the absence of enzyme-inducing agents. Subsequent paracetamol exposure up to 2.6 g daily thrice weekly, in the setting of ongoing malnutrition and fasting as before, did not lead to recurrent liver damage. These findings indicate that paracetamol-related liver damage occurring within recommended dosage guidelines can be a dose-dependent rather than necessarily idiosyncratic phenomenon, at least in the setting of recent fasting and severe malnutrition.