von Meijenfeldt FA, Stravitz RT, Zhang J, et al. - Supporting the first time, evidence for the creation of neutrophil extracellular traps (NETs) in patients with severe acute liver injury (ALI) or acute liver failure (ALF) is presented. Elevated plasma levels of MPO-DNA complexes in ALF patients were linked to a worse outcome, implying that NET formation contributes to disease progression.

• In total, 676 patients with ALF or severe ALI were selected from the US ALF Study Group Registry between 2011 and 2018, of whom 308 patients (45.6%) had acetaminophen-induced ALF.

• Cell-free DNA levels were 7.1-fold higher and MPO-DNA complexes 2.5-fold higher in ALF patients compared with healthy controls.

• Cell-free DNA levels were not related to 21-day transplant-free survival, but they were higher in patients who had more severe disease on admission, as indicated by several laboratory and clinical markers.

• MPO-DNA levels were 30% greater in ALF patients who died or needed an urgent liver transplant.

• In 12/18 evaluable patients, liver tissue from ALF patients stained positive for NETs.