Acetaminophen Use Linked to Adverse Outcomes in Acute Hepatitis A

Adults with acute hepatitis A who receive treatment with acetaminophen have adverse outcomes, including renal replacement therapy and hepatic encephalopathy.

Treatment with acetaminophen is associated with adverse outcomes among individuals with acute hepatitis A (AHA), according to study findings published in Digestive and Liver Disease.

Researchers sourced data from health insurance claims of individuals diagnosed with AHA. The researchers also collected information on patients’ exposure to acetaminophen and assessed complications.

The study defined exposure to acetaminophen as any prescription claims for acetaminophen-containing drugs during the AHA episode. Participants were assessed for adverse outcomes, defined as implementing renal replacement therapy, encephalopathy and/or brain edema, respiratory failure, and liver transplantation.

Investigators identified 43,500 eligible individuals from the data. They used Fisher’s exact test and the Mann-Whitney test to address and categorize variables. They performed univariable and used multivariable logistic regression analyses, and they performed propensity score matching using psmatch2 of STATA. SAS 9.4 or STATA ver. 14.2 were used for statistical analysis.

[O]ur nationwide cohort of AHA revealed an association between APAP exposure and increased adverse outcomes compared to NSAID control.

Adverse outcomes were identified in 593 of 43,500 patients (1.4%). Renal replacement therapy was the most common adverse event (n=418), followed by hepatic encephalopathy and/or brain edema (n=208), mechanical ventilation (n=178), and liver transplantation (n=55).

The researchers noted that exposure to acetaminophen or nonsteroidal anti-inflammatory drugs (NSAIDs) was associated with an increase in adverse outcomes (odds ratio [OR], 5.66; 95% CI, 5.63-5.69) and for acetaminophen and NSAIDs exposure (OR, 2.90; 95% CI, 2.88-2.92).

Investigators examined participants who had exclusive exposure to acetaminophen (n=9,134) vs those with exclusive exposure to NSAIDs (n=2,636). The acetaminophen-only group showed a higher proportion of hospitalization than the NSAID-only group (98.8% vs 92.4%; P <.0001). The acetaminophen-only groups had more adverse outcomes than the NSAID-only group (2.7% vs 2.0%; P = .030).

The results were consistent when controlling for variables such as age, sex, and other health conditions.

Study limitations include a lack of specificity about participants and potential inaccuracies in the data due to the nature of drawing information from claims data.

“In conclusion, our nationwide cohort of AHA revealed an association between APAP [acetaminophen] exposure and increased adverse outcomes compared to NSAID control,” study authors wrote.


Park GC, Chung JW, Jang ES, Kim J-W. Association between adverse outcomes of hepatitis A and acetaminophen use: a population-based cohort study. Dig Liver Dis. Published online April 21, 2023. doi:10.1016/j.dld.2023.03.017