Researchers shed new light on how paracetamol causes liver damage

Scientists have known for decades that paracetamol in large amounts is toxic the liver, but until now its
mechanism of poisoning has eluded them.

As well as providing insights into how an excess dose of this common painkiller causes poisoning that
can be difficult to treat and can prove fatal, the new findings could also open doors to the development of
new drugs for liver damage.

Dr Leonard Nelson, of Edinburgh University, said: “Paracetamol is the world’s preferred pain remedy. It’s
cheap and considered safe and effective at therapeutic dose.

However drug-induced liver damage remains an important clinical problem and a challenge for
developing safer drugs.

Our findings reinforce the need for vigilance in paracetamol use and could help discover how harm
caused by its adverse use might be prevented.”

The study, published in Scientific Reports, looked at the impact of paracetamol on liver cells in human
and mouse tissue.

Experiments showed in certain settings the drug can damage the liver by harming vital structural
connections between adjacent cells in the organ.

When these cell wall connections, known as tight junctions, are disrupted the liver tissue structure is
damaged, cells are unable to function properly and they may die.

This type of cell damage is known to occur in liver conditions including hepatitis, cirrhosis and cancer, but
until now it was not linked to paracetamol toxicity.

The researchers now aim to develop a reliable method of using human liver cells as an alternative to
animal testing.

They then will seek to examine how varying paracetamol doses and timescales affect toxicity in the liver
and identify potential targets for new drugs.

Co-author Dr Pierre Bagnaninchi said: “Although liver damage caused by paracetamol toxicity has been
the subject of intense study for 40 years, recent developments in biosensor technology are enabling a
fuller picture of the biological mechanisms involved.”

Paracetamol is an effective treatment for mild to moderate pain and fever in adults and children, when
used as directed in product information.

The maximum dose within a 24-hour period must never be exceeded.

Even taking one or two more tablets than recommended can cause serious liver damage and possibly
death. Paracetamol overdose is one of the leading causes of liver failure.
Adults can usually take one or two 500mg tablets every 4-6 hours, but shouldn’t take more than 4g (eight
500mg tablets) in the space of 24 hours.

Children under 16 need to take a lower dose, depending on their age or weight – check the packet or
leaflet, or ask a pharmacist or doctor for advice.

For very young children, paracetamol liquid is given using a measuring spoon or an oral syringe.

Serious paracetamol overdoses occur twice as often in Britain than the rest of Europe.

Paracetamol-linked liver failures, so severe that the patient needs a transplant, happen in the UK eight
times more than in Holland, twice as often than in France, and 66 times more than in Italy.

Last year a study of seven countries commissioned by the European Medicines Agency found only
Ireland came out worse than Britain.

Paracetamol overdoses represent 20 per cent of liver transplants across Europe, but rise to 52 per cent in
Ireland and 28 per cent in the UK, dropping to 1 per cent in Italy.