Association between adverse outcomes of hepatitis A and acetaminophen use: A population-based cohort study.

Abstract

Acetaminophen (APAP) may cause acute liver injury with therapeutic doses in high-risk conditions such as chronic alcohol consumption or malnutrition. In acute hepatitis A (AHA), however, the safety of APAP has not been fully established. This study examined the potential association between APAP use and clinical outcomes of AHA in a nationwide and hospital-based cohort. Adult patients with AHA were identified from claims data of South Korean national healthcare insurance between 2008 and 2016 (n=43,500). Logistic regression models were used to compare the risk of adverse outcomes (renal replacement therapy, hepatic encephalopathy and/or brain edema, mechanical ventilation, and liver transplantation) in patients exposed to APAP against control and patients exposed to NSAIDs. A propensity score (PS)-matched hospital-based AHA cohort (n=146) was assessed for biochemical profiles after exposure to APAP or NSAIDs. AHA patients were exposed to APAP or NSAIDs in 26.4% and 11.5% of cases, respectively. Compared to NSAID treatment, APAP exposure was associated with a higher incidence of hospitalization (98.8% vs. 92.4%; p<0.0001). APAP exposure was independently associated with increased adverse outcomes (odds ratio [OR]=5.66, p<0.0001 against control; OR =1.67, p=0.0015 against NSAIDs). PS-matched hospital cohort showed higher peak serum bilirubin levels (7.0vs. 5.3mg/dL; p=0.03) and a longer time to recovery of jaundice after APAP use than with NSAID use. APAP exposure was associated with increased adverse outcomes in a nationwide AHA cohort.