Because of the extensive use of this drug, further evaluation of acute liver injury with therapeutic doses of acetaminophen (≤6g/day) is required.
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.
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.
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.
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.