Association of Acetaminophen (Paracetamol) Use With Severity and Outcomes in Patients With Viral Hepatitis-Associated Acute Liver Failure

William M Lee; Carson Barnard; Jody A Rule; Babak J Orandi; Laura P James; R Todd Stravitz; Valerie Durkalski; Robert J Fontana; Acute Liver Failure Study Group

doi:10.14309/ajg.0000000000002941

Association of Acetaminophen (Paracetamol) Use With Severity and Outcomes in Patients With Viral Hepatitis-Associated Acute Liver Failure

Am J Gastroenterol. 2024 Jul 12. doi: 10.14309/ajg.0000000000002941. Online ahead of print.

Authors

William M Lee¹, Carson Barnard¹, Jody A Rule¹, Babak J Orandi², Laura P James³, R Todd Stravitz⁴, Valerie Durkalski⁵, Robert J Fontana⁶; Acute Liver Failure Study Group

Affiliations

¹ Division of Digestive and Liver Diseases, UT Southwestern Medical Center, Dallas, Texas, USA.
² Departments of Surgery and Medicine, New York University, New York, New York, USA.
³ Arkansas Children's Hospital, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA.
⁴ Section of Hepatology, Virginia Commonwealth University, Richmond, Virginia, USA.
⁵ Department of Public Health, Medical University of South Carolina, Charleston, South Carolina, USA.
⁶ Division of Gastroenterology and Hepatology, University of Michigan Medical School, Ann Arbor, Michigan, USA .

PMID: 38994834
DOI: 10.14309/ajg.0000000000002941

Abstract

Introduction: Acute viral hepatitis (AVH) comprises 11% of acute liver failure (ALF) in North America while acetaminophen (APAP) toxicity represents 46%. The use of APAP to treat prodromal hepatitis symptoms is common. It is unknown if concurrent APAP use impacts liver injury in AVH-induced ALF.

Methods: In this prospective, multicenter cohort study, 356 patients meeting criteria for AVH including hepatitis A, B, Epstein-Barr virus, and herpes simplex virus, all leading to ALF (hepatic encephalopathy after acute illness, international normalized ratio ≥1.5), or acute liver injury (acute liver injury, international normalized ratio >2.0, no hepatic encephalopathy) were reviewed for evidence of APAP use: APAP ingestion history or measurement of serum APAP level or APAP-CYS adducts, a specific biomarker released into blood with APAP injury. Patients were grouped by APAP exposure level, from high (measurable APAP levels or toxic APAP-CYS), medium (therapeutic APAP-CYS), low (history of APAP ingestion only and/or barely detectable APAP-CYS), or no exposure recorded.

Results: Two hundred five of 356 patients (57.5%) with AVH-ALF had evidence of APAP use: 87 out of 356 (24%) demonstrated high or medium exposures. The aminotransferase and bilirubin levels of high/medium group resembled a mixed APAP-viral injury. Mortality was the highest (51.6%, 21.4%, 28.8%, and 30.5%), and transplant-free survival was the lowest (22.6%, 44.6%, 41.5%, and 40.4%) in the high exposure group compared with medium, low, and no exposure groups. However, the specific comparisons of mortality and transplant-free survival between the high exposure and no exposure groups were not statistically different even after adjusting for baseline patient characteristics differences.

Discussion: APAP use in AVH-ALF is common and may negatively impact outcomes compared with little or no APAP exposure. Prospective studies of the safest and effective dose of APAP to use in patients with AVH are needed.

Abstract

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