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

ABSTRACT

BACKGROUND/AIMS: Acute viral hepatitis (AVH) comprises 11% of acute liver failure (ALF) in North America while acetaminophen (APAP) toxicity represents 46%. Use of APAP to treat prodromal hepatitis symptoms is common. It is unknown if concurrent APAP use impacts liver injury in AVH-induced ALF. PATIENTS AND METHODS: In this prospective, multicenter cohort study, 356 patients meeting criteria for AVH including hepatitis A, B, EBV, and HSV, all leading to ALF (hepatic encephalopathy (HE) after acute illness, INR ≥ 1.5), or acute liver injury (ALI, INR >2.0, no HE) 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: 205/356 (57.5%) of AVH-ALF patients had evidence of APAP use 87/356 (24%) demonstrated High or Medium exposures. The High/Medium group's aminotransferase and bilirubin levels resembled a mixed APAP-viral injury. Mortality was highest (51.6%, 21.4%, 28.8%, 30.5% and transplant-free survival (TFS) lowest (22.6%, 44.6%, 41.5%, 40.4%) in the High Exposure group compared to Medium, Low, and No Exposure groups. However, the specific comparisons of mortality and TFS between the High and No Exposure groups were not statistically different even after adjusting for baseline patient characteristics differences. CONCLUSIONS: APAP use in AVH-ALF is common and may negatively impact outcomes compared to little or no APAP exposure. Prospective studies of the most safe and effective dose of APAP to use in patients with AVH are needed.