Sleep disorders are associated with acetaminophen-induced adverse reactions and liver injury

Risk factors related to the development of acetaminophen (APAP)-induced adverse reactions and liver injury remain uncertain. Sleep disorders have been linked to some health outcomes. This study examined the associations of sleep disorders with APAP-induced adverse reactions or liver injury and the possible mechanisms. From NIS database, adverse reactions, liver injury and sleep disorders were identified. Factors associated with the risk of the total adverse effects or liver injury were examined with logistic regression. From Gene Expression Omnibus database, datasets GSE111828, containing transcriptome data based on RNA-seq analysis from liver samples extracted from mice post APAP administration, and GSE92913, containing transcriptome data based on microarray analysis from liver samples extracted from mice with sleep deprivation, were analyzed. A total of 4372754 patients without and 91314 patients with sleep disorders were eligible for analyses. Both before and after propensity score matching, APAP-induced adverse reactions were higher in patients with sleep disorders than in patients without. In multivariate regression, sleep disorders were associated with higher odds of APAP-induced adverse reactions (adjusted OR [aOR] 2.005, 95 % CI 1.343-2.995) and liver injury (aOR 2.788, 95 % CI 1.310-5.932). Genes that were enriched in bile secretion and retinol metabolism and PPAR signaling pathways were basically down-regulated in livers of mice after APAP administration and livers of mice with sleep deprivation. This study shows that sleep disorders may be novel independent risk factors for APAP-associated adverse reactions and liver injury and provides bioinformation linking sleep disorders to increased risk of APAP-induced liver injury.