Public Health

Acetaminophen-related liver failure rising sharply in US

Last Updated: 2005-12-06 13:27:59 -0400 (Reuters Health)

NEW YORK (Reuters Health) - The percentage of acute liver failure cases due to acetaminophen overdose has increased from 1998 to 2003, with unintentional overdose accounting for at least half of these cases, a new US study shows.

People with chronic pain, depression and those who abuse substances, including alcohol, may be particularly at risk for unintentional acetaminophen overdose, Dr. Anne M. Larson of the University of Washington in Seattle and colleagues conclude.

"Efforts to limit over-the-counter (OTC) packaging size and to restrict the prescription of narcotic-acetaminophen combinations (or to separate the narcotic from the acetaminophen) may be necessary to reduce the incidence of this increasingly recognized but preventable cause of acute liver failure in the United States," Dr. Larson and her team write in the December issue of Hepatology.

The researchers analyzed data on 662 consecutive patients treated for acute liver failure at 22 US tertiary care centers between 1998 and 2003. During that time, the annual percentage of acute liver failure due to acetaminophen rose from 28% to 51%.

Among the 275 cases determined to be acetaminophen-related, 48% were unintentional overdoses, 44% were suicide attempts, and intent was unknown in 8%. Many characteristics of the unintentional and intentional overdose groups were similar, while their clinical outcomes were not different.

Patients who unintentionally overdosed were older than those who attempted suicide (median 38 vs. 32 years), more likely to use several products containing acetaminophen (38% vs. 5%) and took longer to seek care after symptoms developed (4 days vs. 1 day). Seventy-nine percent reported taking the medications for pain.

Thirty-five percent of patients who overdosed unintentionally had a history of substance abuse, compared with 31% of patients who had attempted suicide. Depression was reported by 24 percent who unintentionally overdosed, while 45% of patients who intentionally overdosed were.

Among patients who overdosed unintentionally, 63% were using acetaminophen-narcotic compounds, while 38% were taking two or more products containing acetaminophen.

"Our data suggest that there is a narrow therapeutic margin, and that consistent use of as little as 7.5 g/day may be hazardous," they write.

In an editorial accompanying the study, Dr. John G. O'Grady of King's College Hospital in London points out that a 1998 rule in the UK restricting OTC sales of acetaminophen to 16 g led to a 30% reduction in acute liver failure admissions related to the drug, while France's rule limiting sales to 8 g has also been effective.

"The required judgment from society, the medical profession, and other interested parties, is whether that level of restriction is too high a price to pay," he concludes.

Hepatology 2005;42:1252-1254,1364-1372.