Serum nucleosomes have been suggested to be markers for cell death and apoptosis. Increased hepatocyte apoptosis can be demonstrated in acute liver failure (ALF) as well as acute-on-chronic liver failure (ACLF). We investigated the relevance of nucleosomes in the setting of acute hepatic failure. Further, we studied the effects of the molecular adsorbent recirculating system (MARS) on this marker of cell death. We measured serum nucleosome concentrations with ELISA in 12 patients with ACLF and 7 patients suffering from ALF, with 14 patients experiencing stable chronic hepatic failure (CHF) as controls. In a subset of 8 ACLF and ALF patients treated with MARS, nucleosomes were determined immediately before and after the first MARS session. Baseline nucleosome serum concentrations were significantly increased in ACLF and ALF patients as compared with CHF patients (P = .0161 and P = .0037, respectively). There was no significant difference between the ALF and ACLF groups. Moreover, serum nucleosome levels did not change significantly during MARS treatment in ALF and ACLF patients. Serum nucleosome levels therefore may be useful to discern acute from chronic hepatic failure or to monitor the course and the severity of the disease. Our results, however, warrant further larger clinical studies regarding the clearance of nucleosome in artificial liver-assist devices and to assess their role in acute hepatic failure.