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Review
. 2018 Feb;74(2):147-160.
doi: 10.1007/s00228-017-2356-6. Epub 2017 Oct 24.

Are some people at increased risk of paracetamol-induced liver injury? A critical review of the literature

Thomas M Caparrotta  1 , Daniel J Antoine  2 , James W Dear  3
Affiliations
Review

Are some people at increased risk of paracetamol-induced liver injury? A critical review of the literature

Thomas M Caparrotta et al. Eur J Clin Pharmacol. 2018 Feb.

Abstract

Purpose: Paracetamol is one of the world's most commonly used drugs. In overdose, it is well established to be hepatotoxic. The aim of this review was to identify factors that have been, or actually are, associated with the development of liver injury after paracetamol exposure in humans.

Method: Google Scholar and PubMed were searched on various dates between December 2016 and March 2017. Papers identified had their references analysed for further studies that might be relevant.

Results: At the time of writing, there was little good quality clinical evidence-from studies of paracetamol overdose or therapeutic use-to suggest that any groups of people are relatively protected from, or are at greater risk of, liver injury. The factors that were historically used to indicate higher risk in the UK have no good quality clinical evidence to support their re-introduction into clinical practice. The safe (and still effective) oral dose of paracetamol in patients weighing less than 50 kg has not been established.

Conclusion: There is no patient group that is unequivocally at elevated risk of paracetamol-induced liver toxicity. We propose two clinical scenarios that warrant further research. Firstly, there is a need to establish whether the dose of paracetamol should be reduced in patients with low body weight. Secondly, if or when genomic information regarding individual patients becomes readily available to inform prescribing, we propose the contribution of the genome to paracetamol toxicity should be re-investigated with robustly designed studies. Such studies could enhance the safe use of one of the most frequently taken drugs.

Keywords: Acetaminophen; DILI; Genomics; Hepatotoxicity; Paracetamol.

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Conflict of interest statement

Dr. Dear is Chief Investigator on a phase 1 commercial-funded clinical trial of an Investigational Medicinal Product for paracetamol overdose (NCT03177395).

Figures

Fig. 1
Fig. 1
Major pathways of paracetamol metabolism
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Fig. 2
Genetic differences and paracetamol metabolism
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Fig. 3
Alcohol’s effect on paracetamol metabolism
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Fig. 4
Potential sites of drug interactions with paracetamol metabolism
See this image and copyright information in PMC

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