Hepatology. 2020 Dec 11. doi: 10.1002/hep.31678. Online ahead of print.
INTRODUCTION: Because of the extensive use of this drug, further evaluation of acute liver injury with therapeutic doses of acetaminophen (≤6g/day) is required.
AIMS: characterize the acute liver injury (ALI) with therapeutic doses (TD) of acetaminophen and determine the host factors associated with disease severity and the predictors of outcome.
DESIGN: All patients admitted with severe acetaminophen-related acute liver injury in our center were included from 2002 to 2019, either due to therapeutic doses or overdose. ALITD was defined as acetaminophen intake <6g/day.
RESULTS: 311/400 patients with acetaminophen-related ALI had overdose and 89 had taken therapeutic doses. The host factors associated with ALITD were fasting ≥1 day (47.5% of ALITD patients vs. 26% in overdose, p=0.001), excess drinking (93.3 vs. 48.5%, p<0.0001) and repeated acetaminophen use (4 vs. 1 day, p<0.0001). Patients with ALITD were older (44 vs. 30.7 years, p<0.0001) and had more severe liver injury. In the overall population, the independent predictors of disease severity were older age, longer duration of acetaminophen intake and excess drinking. 30-day survival was lower in ALITD than in overdose: 87.2±3.6 vs. 94.6±1.3%, p=0.02. Age and the presence of at least one of the King's College Hospital criteria were independent predictors of 30-day survival while the pattern of drug intoxication, excess drinking and bilirubin were not.
CONCLUSION: Acute liver injury with therapeutic doses of acetaminophen is associated with more severe liver injury than overdose. It only occurs in patients with excess drinking and/or fasting. A warning should be issued about the repeated use of nontoxic doses of acetaminophen in patients with those risk factors.