Elevated AAC is rapidly reversed by transplantation and to a lesser degree by standard Ceritinib hemofiltration. Disclosures: Julia Wendon – Consulting: Pulsion, Excalenz William Bernal – Consulting: Vital Therapies Inc The following

people have nothing to disclose: Vishal C. Patel, Beatriz Mateos Muhoz, Elizabeth Sizer, Charalambos G. Antoniades, Christopher Willars, Georg Auzinger Background: Impaired neutrophil function has been demonstrated in acute liver failure and serves as a biomarker involved in organ dysfunction and increase susceptibility to sepsis. However, its role in acute-on-chronic liver failure (ACLF) remains completely unknown. Patients and methods: We assessed phenotypic and functional alterations of neutrophils and their contribution in hepatic injury in 17 hepatitis B virus-related ACLF (HBV-ACLF), 19 alcohol–related ACLF (alcoholic-ACLF), and 42 chronic hepatitis B (CHB) patients in comparison to 18 healthy controls (HC).Neutrophil phagocytic activity (NPA) was determined by the uptake of opsonized E. coli and reactive oxygen species (ROS) production with or without E. coli stimulation.CXCR-1 and CXCR-2 expression was analyzed by flowcytometry, immunohistochemistry (IHC) and qRT-PCR. Results: Percentage

of neutrophils was higher in both HBV and alcoholic-ACLF patients than CHB and HC (Table). Contrarily, NPA was significantly impaired in ACLF along with significant increase in ROS. Flowcytometry and IHC showed up-regulated CXCR-1 and 2 in ACLF. In ACLF, intrahepatic HSP assay CXCR-1 and 2 gene expression was higher more than 6 fold (p<0.00) with a significant increase in pro-inflammatory cytokines (IL-6, IL-17, IL-23, CXCL-8, CCL-20 and GM-CSF). Role of neutrophils in hepatic injury was determined by co-culturing of LPS stimulated

neutrophils or their supernatant with HepG2 cells. As compared to controls, activated neutrophils from ACLF significantly induced early apoptosis (p<0.04, 0.05) and necrosis (p<0.00, 0.00) of HepG2 cells by direct contact as well as cytokine/ ROS dependent mechanisms. Conclusions: ACLF patients have increased frequency of neutrophils, with high expression of migration receptors CXCR1/CXCR2. These activated neutrophils produce high ROS but have impaired phagocytic activity with high MCE pro-inflammatory cytokine propagating hepatic injury and liver failure. Neutrophil functional markers represent a powerful tool for drug targets and clinical management of ACLF patients. Phenotypic and functional characterization of neutrophils in different diseased groups Disclosures: The following people have nothing to disclose: Arshi Khanam, Nirupma Trehan Pati, Peggy Riese, Archana Rastogi, Carlos A. Guzman, Shiv K. Sarin The type II bacterial clustered, regularly interspaced, palindromic repeats (CRISPR)-associated (Cas) system has been engineered into a powerful genome editing tool consisting of the Cas9 nuclease and a single guide RNA (sgRNA).