IL-8+ neutrophils drive inexorable inflammation in severe alcohol-associated hepatitis [scRNA-seq]

Patients with alcohol-associated liver cirrhosis (AC) may develop severe alcohol-associated hepatitis (sAH), but the mechanisms underlying the transition from AC to sAH still remain unclear. We performed single cell RNA (scRNA) sequencing analysis of livers and peripheral white blood cells (WBC) from sAH and AC patients. We found that the significant difference between sAH and AC was that sAH livers had a markedly higher number of neutrophil subsets than AC livers. Thus, we further focused on the neutrophil cluster and found two distinct sAH-specific liver neutrophils are notably characterized by heightened expression of CXCL8 (IL-8) defined as IL-8+ neutrophils blood. Our current study has demonstrated that sAH had self-sustaining IL-8+ neutrophil accumulation that likely drives inexorable liver inflammation and failure in sAH. Based on our study, we believe targeting IL-8+ neutrophils is a promising therapeutic strategy for sAH. We performed scRNA sequencing analysis of 6 liver tissues and 7 peripheral white blood cells (WBC) from sAH and AC patients, including 5 sAH livers, 4 sAH WBCs; 1 AC liver, and 3 AC WBCs.