The study investigates the mechanisms underlying the progression from alcohol-associated cirrhosis (AC) to severe alcohol-associated hepatitis (sAH). Using single-cell RNA-Seq (scRNA-Seq) analysis, the researchers identified a significant increase in the number of neutrophils, particularly IL-8+ neutrophils, in sAH livers compared to AC livers. These IL-8+ neutrophils exhibit unique gene profiles and are characterized by heightened expression of CXCL8, a key chemokine for neutrophil activation. The study also found that IL-8+ neutrophils in sAH are driven by upregulation of IL-1β, TNF-α, and transcription factors such as REL and FOS. Additionally, the accumulation of IL-8+ neutrophils is associated with increased levels of chemokines like CXCL8, CXCL6, and CXCL5. The findings suggest that targeting IL-8+ neutrophils could be a promising therapeutic strategy for sAH by blocking IL-8 signaling or the inflammatory signals that induce IL-8.The study investigates the mechanisms underlying the progression from alcohol-associated cirrhosis (AC) to severe alcohol-associated hepatitis (sAH). Using single-cell RNA-Seq (scRNA-Seq) analysis, the researchers identified a significant increase in the number of neutrophils, particularly IL-8+ neutrophils, in sAH livers compared to AC livers. These IL-8+ neutrophils exhibit unique gene profiles and are characterized by heightened expression of CXCL8, a key chemokine for neutrophil activation. The study also found that IL-8+ neutrophils in sAH are driven by upregulation of IL-1β, TNF-α, and transcription factors such as REL and FOS. Additionally, the accumulation of IL-8+ neutrophils is associated with increased levels of chemokines like CXCL8, CXCL6, and CXCL5. The findings suggest that targeting IL-8+ neutrophils could be a promising therapeutic strategy for sAH by blocking IL-8 signaling or the inflammatory signals that induce IL-8.