Acetaminophen syn. Paracetamol: Acute Liver Injury and Acute on Chronic Liver Failure with Case Analysis and Causality Assessment Using RUCAM

Abstract

The use of acetaminophen, also known as paracetamol, may affect the liver in variable ways, either as an asymptomatic liver adaptation in the sense of tolerance or an acute liver injury due to an idiosyncratic toxicity or intrinsic toxicity, an acute liver failure (ALF) confined to cases without preexisting liver disease, or an acute on chronic liver failure (ACLF) in patients with preexisting chronic liver disease. This broad spectrum is not uncommon among hepatotoxins such as other drugs or herbs, requiring clear diagnostic differentiation of the disease stages. With respect to acetaminophen, the intrinsic liver injury type is the most common form followed by ALF, both occurring after an overdose. In this case series, causality for acetaminophen was established at variable degrees using the liver specific causality assessment method RUCAM (Roussel Uclaf Causality Assessment Method). As expected, no case of ACLF due to acetaminophen was found in the scientific literature because in cohort studies of ALF the cases were intentionally restricted to those without preexisting liver diseases. Nevertheless, it is conceivable that some patients had preexisting liver disease like alcoholic liver disease and experienced ACLF caused by acetaminophen overdose. In future cases of patients with ALF caused by acetaminophen, preexisting liver disease should be systematically sought for, assisted by RUCAM in its updated version to assess causality. Overall, ACLF due to acetaminophen overdose must be recognized and clearly differentiated from ALF on healthy liver because both conditions may show differences in clinical outcome and possibly require different therapeutic options, assuming a less favorable course of ACLF compared to ALF. Members of all Acute Liver Failure Study Groups should be encouraged to initiate a prospective study on acetaminophen induced ACLF.