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Review
. 2020 Apr 27;12(4):125-136.
doi: 10.4254/wjh.v12.i4.125.

Liver injury induced by paracetamol and challenges associated with intentional and unintentional use

Laura Rotundo  1 , Nikolaos Pyrsopoulos  2
Affiliations
Review

Liver injury induced by paracetamol and challenges associated with intentional and unintentional use

Laura Rotundo et al. World J Hepatol. .

Abstract

Drug induced liver injury (DILI) is a common cause of acute liver injury. Paracetamol, also known as acetaminophen, is a widely used anti-pyretic that has long been established to cause liver toxicity once above therapeutic levels. Hepatotoxicity from paracetamol overdose, whether intentional or non-intentional, is the most common cause of DILI in the United States and remains a global issue. Given the increased prevalence of combination medications in the form of pain relievers and antihistamines, paracetamol can be difficult to identify and remains a significant cause of acute hepatotoxicity, as evidenced by its contribution to over half of all acute liver failure cases in the United States. This is especially concerning given that, when co-ingested with other medications, the rise in serum paracetamol levels may be delayed past the 4-hour post-ingestion mark that is currently used to determine patients that require medical therapy. This review serves to describe the clinical and pathophysiologic features of hepatotoxicity secondary to paracetamol and provide an update on current available knowledge and treatment options.

Keywords: Acute liver failure; Drug-induced liver injury; Hepatotoxicity; Paracetamol.

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Conflict of interest statement

Conflict-of-interest statement: Dr. Pyrsopoulos reports grants from Allergan, grants from Bayer, grants from Beigene, grants from Bristol Myers, grants from Confirm, grants from Conatus, grants from Intercept, grants from Mallinckrodt, grants from Novartis, grants from Resusix, grants from Saro, grants from Valeant, grants from Gilead, grants from Exelixis, grants from Hologic, grants from Shire, grants from Genfit, grants from Prometheus, outside the submitted work. Dr. Rotundo certifies that she has no affiliations with or involvement in any organization or entity with any financial interest or non-financial interest in the subject matter or materials discussed in this manuscript.

Figures

Figure 1
Figure 1
Paracetamol metabolism pathways and breakdown into N-acetyl-p-benzoquinone imine, by cytochrome P450 2E1. N-acetyl-p-benzoquinone imine is the toxic metabolite produced from paracetamol metabolism when the other two conjugation pathways become over-saturated. The resultant toxic N-acetyl-p-benzoquinone imine byproduct is converted into nontoxic metabolites by glutathione, which is regenerated by N-acetylcysteine. NAPQI: N-acetyl-p-benzoquinone imine; CYP2E1: Cytochrome P450 2E1; NAC: N-acetylcysteine.
Figure 2
Figure 2
Factors that pre-dispose patients to increased paracetamol toxicity.
Figure 3
Figure 3
Flowchart depicting the management pathway for acute paracetamol overdose/ toxicity. ALT: Aminotransferase; AST: Aspartate aminotransferase.
See this image and copyright information in PMC

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