Hepatocellular damage

liver411

Q J Med 2003; 96: 787-791
© 2003 Association of Physicians

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Review

Hepatocellular damage from non-steroidal anti-inflammatory drugs

N. O'connor1, P.I. Dargan2 and A.L. Jones2
From the 1Emergency Department and 2National Poisons Information Service
(London), Guy's and St Thomas' NHS Trust, London, UK

Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used for the
management of rheumatological disorders, and as analgesics and antipyretics.
Hepatotoxicity is an uncommon, but potentially lethal complication, which
usually occurs within 12 weeks of starting therapy. It can occur with all
NSAIDs, but appears to be more common with diclofenac and particularly
sulindac. Female patients aged >50 years, with autoimmune disease, and those
on other potentially hepatotoxic drugs, appear to be particularly
susceptible. Liver function test abnormalities generally settle within 4-6
weeks of stopping the causative drug. However, some patients may develop
acute liver failure and successful orthotopic liver transplantation may be
undertaken in such patients. Recent in vitro animal studies have shown that
the mechanism of diclofenac toxicity relates both to impairment of ATP
synthesis by mitochondria, and to production of active metabolites,
particularly n,5-dihydroxydiclofenac, which causes direct cytotoxicity.
Mitochondrial permeability transition (MPT) has also been shown to be
important in diclofenac-induced liver injury, resulting in generation of
reactive oxygen species, mitochondrial swelling and oxidation of NADP and
protein thiols. Physicians and hepatologists must be vigilant to the
hepatotoxic potential of any NSAID, as increased awareness, surveillance and
reporting of these events will lead to a better understanding of the risk
factors and the pathophysiology of NSAID-related hepatotoxicity.


Address correspondence to Dr A.L. Jones, National Poisons Information
Service (London), Guy's and St Thomas' NHS Trust, Avonley Road, London SE14
5ER. e-mail: [email protected]