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Risk Factors Predict Acetaminophen Hepatotoxicity


 

Patients hospitalized for acetamino-phen overdose had a 4.5% rate of acetaminophen-induced hepatotoxicity in a population-based study, according to Dr. Robert P. Myers and his associates.

In a multivariate analysis of residents of Calgary and southern Alberta (Canada) during 1995–2004, significant risk factors for acetaminophen hepatotoxicity were alcohol abuse, preexisting liver disease, and unintentional ingestion, the authors said (Clin. Gastroenterol. Hepatol. 2008 August [Epub doi:10.1016/j.cgh.2008.02.053

“These findings highlight the necessity of educational initiatives regarding the potential hazards of acetaminophen, particularly in the high-risk groups that we have identified.

In addition, clear labeling of medications with their acetaminophen content must be ensured so as to minimize unintentional overdoses,” wrote Dr. Myers, from the liver unit in the department of medicine at the University of Calgary, and his colleagues.

The findings also highlighted the substantial clinical impact that acetaminophen-induced hepatotoxicity can have. At the same time, the findings “reassuringly” showed that acetaminophen hepatotoxicity is uncommon following an overdose, supporting the “relatively benign” nature of most overdoses, the authors said. More than 95% of the overdose episodes did not result in liver damage.

The researchers used administrative databases to track the outcomes of patients hospitalized for acetaminophen overdose in Calgary and southern Alberta during a 10-year period.

The analysis identified 1,543 patients who had 1,680 hospital admissions for acetaminophen overdose during the study period. About 68% were women, and their average age was 26 years, with a range of 0-96 years old. Depression was diagnosed in 55% of the patients, and 34% were diagnosed with alcohol abuse. Underlying liver disease was found in 3% (46 patients), including 11 patients with cirrhosis (0.7%).

The overdoses were deemed intentional in 85%, unintentional in 13%, and other in 2%. The rate of unintentional overdoses rose with age. Among patients younger than 30 years, 9% had unintentional overdoses, which rose to 15% among those aged 30–49 years, and 30% among patients aged 50 years or older (Clin Gastroenterol Hepatol. doi:10.1016/j.cgh.2008.02.053

Patients with unintentional overdoses had a lower prevalence of depression—18%, compared with 60% among depressed patients—but the prevalence of alcohol abuse was similar among those whose overdoses were unintentional (36%) and intentional (33%). Liver disease was more common among the patients with unintentional overdoses, 14%, than in those with intentional overdoses, 1.3%.

The incidence of hepatotoxicity increased among patients with two or more of the three independent risk factors for developing hepatotoxicity: alcohol abuse, preexisting liver disease, and unintentional overdose. In patients with none of these risk factors, 1.3% developed hepatotoxicity. In those with one risk factor, the hepatotoxicity rate rose to 5%. It was 19% in patients with two risk factors and 52% in those with all three risk factors.

A multivariate analysis of long-term survival among the patients hospitalized for acetaminophen overdose showed that older age, male gender, lower income, greater number of comorbidities, and acetaminophen-triggered hepatotoxicity were all significantly linked with lower survival.

Recent data suggest that the incidence of acetaminophen overdose is on the rise. Data from Calgary and southern Alberta indicated a 24% increase in the rate of unintentional overdoses during 1995–2004.

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