Is paracetamol hepatotoxic at normal doses?

We note that the number of registrations for hepatic transplantation for paracetamol overdose found in SALT (Study of Acute Liver Transplantation) in the UK1—63 cases in 2005-07 (5.25 cases per quarter)—was the same as that reported by Hawton and colleagues.2

However, in the UK and the other European countries included in the SALT study, paracetamol had been used in the 30 days before the first symptoms in several acute liver failures that led to registration for transplantation (ALFT) not related to overdose. There were 24 cases in the UK and 49 in France, for example. Using the same criteria as for other “known hepatotoxic agents,” such as non-steroidal anti-inflammatory drugs (NSAIDs), we found that non-overdose paracetamol was associated with a three times higher rate of ALFT than all NSAIDs pooled, or individual NSAIDs such as diclofenac or nimesulide. This was true whether the denominator was in patient years or individual patients.3

Perhaps we should start looking into hepatotoxicity associated with paracetamol at normal doses? Does this have anything to do with chronic glutathione depletion and increased risk from other toxins, as was hypothesised for asthma?4

Is paracetamol like the postman: so obviously innocuous and commonplace that it becomes invisible?