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SALT trial: Paracetamol overdose leads to ALF and registry on transplantation lists

In the Study of Acute Liver Transplantation trial, researchers found that paracetamol overdose was prevalent and an indicator for all-cause acute liver failure leading to registration on transplantation lists among various European countries, especially in Ireland and the United Kingdom, according to newly published data.

“Most studies of paracetamol overdose originate from emergency departments or hepatology units, and give relative rates of transplantation relative to all overdoses,” the researchers wrote. “Very few have attempted to identify all cases of overdose [acute liver failure leading to registration on transplantation lists] within one or several countries. We took advantage of [the Study of Acute Liver Transplantation trial] to quantify paracetamol-related overdose leading to [acute liver failure leading to registration on transplantation lists] in different countries in Europe.”

Sinem Ezgi Gulmez

Researchers, including Sinem Ezgi Gulmez, MD, PhD, associate professor of pharmacology at the University of Bordeaux, France, evaluated data of all patients with acute liver failure leading to registration on transplantation lists (ALFT) entered in transplant registries across France, Greece, Ireland, Italy, the Netherlands, United Kingdom and Portugal between 2005 and 2007. The researchers concentrated on the rate of paracetamol overdose and compared all adult overdose-related ALFT, with or without suicidal intent, with the amount of paracetamol sold in that specific country, according to the research.

Of all 9,479 cases registered for transplant, 600 were ALFT and 114 were overdose, with 97.3% of the cases (n = 111) having paracetamol as the toxic drug involved.

The average rate of ALFT in all seven countries over 3 years was one case per 6 million residents annually, with the rate being the highest in Ireland (one case for every 280,000 residents) compared with the lowest rate found in Italy (one case for every 60 million residents).

The highest rates of overdose ALFT per metric ton of paracetamol sold or per resident was found in Ireland and the UK, according to the research.

“Overall, we found a six times higher risk in Ireland and a two-fold higher risk in the UK compared to the average of the countries participating in the study,” Gulmez said in a press release. “Since we do not have event rates for overdoses not leading to liver failure, we cannot conclude anything about the rates of non-ALFT overdoses in the different countries, but indicators point to more common use of paracetamol for self-poisoning in these countries.”

Paracetamol overdose accounted for 20% of all causes of this type of ALFT across Europe, but increased to 52% in Ireland and 28% in the UK, but only 1% in Italy. While no paracetamol overdose cases were found in Greece, France had the highest per-person use of paracetamol and the third-lowest ALFT rate.

“The differences in the figures for harm caused by paracetamol within different countries in Europe are not marginal, and suggest that there are some underlying causes,” Gulmez said. “Paracetamol overdose is a serious public health issue and we should start looking into hepatotoxicity associated with paracetamol at normal doses.” – by Melinda Stevens

Disclosure: Gulmez reports no relevant financial disclosures. Please see the full study for a list of all other authors’ relevant financial disclosures.