Rubin JB, et al. - This study was performed to describe the sex differences in acetaminophen-induced hepatotoxicity. The more common incidence of acetaminophen-induced acute liver injury (ALI) and acute liver failure (ALF) were observed among women. Compared to men, women had greater critical care needs, and increased risk for severe hepatic encephalopathy (HE), which could be due in part to increased use of sedatives.

Methods

• Between January 2000 through September 2016, the researchers collected data from the Acute Liver Failure Study Group cohort, a national registry of 32 academic medical centers in North America of adults with ALI or ALF.
• This study included 1,162 patients with acetaminophen-induced ALI (n=250) or acetaminophen-induced ALF (n=912).
• Data on patient presentation, disease course, demographics, medical and psychiatric history, medication use, substance use, and details of acetaminophen ingestion were analyzed.
• They evaluated sex differences in continuous and categorical variables by Wilcoxon rank-sum and Χ² analysis or the Fisher exact test.
• To evaluate sex differences in the presentation and clinical course of acetaminophen-induced acute liver injury or liver failure was the primary aim.
• The secondary goal was to compare overall and transplant-free survival between sexes.

Results

• Acetaminophen-induced ALI (68%) or ALF (76%) was observed mostly in women.
• Compared to men, higher proportions of women had psychiatric disease (60% of women vs 48% of men, P < .01) and had co-ingestion with sedating agents (70% of women vs 52% of men, P < .01)-more than half of which were opioids.
• Severe hepatic encephalopathy (HE) (68% of women vs 58% of men) and intubation requirement (67% of women vs 59% of men, P values <.03) were observed in higher proportions of women.
• Higher proportions of women used vasopressors (26% of women vs 19% of men, P=.04) or mannitol (13% of women vs 6% of men, P < .01).
• Proportions of male vs female patients with transplant-free survival were similar (68%).
• Women had higher risk of severe HE (adjusted odds ratio [AOR], 1.66; 95% CI, 1.17-2.35) in adjusted analysis.
• A significant interaction was found between sex and co-ingestion of sedating agents (P < .01).
• Co-ingestion increased odds of severe HE in women 2-fold (AOR, 1.86; 95% CI, 1.28-2.69; P < .01) but not in men (AOR; 0.62, 95% CI 0.34–1.13; P=.12).