Alcohol-associated hepatitis (sAH) is a severe form of alcohol-related liver disease with high mortality and limited treatment options. A study identifies that IL-8⁺ neutrophils play a critical role in the progression from alcohol-associated cirrhosis (AC) to sAH. Using single-cell RNA sequencing, researchers found that sAH livers have significantly higher numbers of neutrophils compared to AC livers, with these neutrophils expressing high levels of IL-8. These IL-8⁺ neutrophils are associated with increased TNF-α, IFN-γ, and inflammatory pathways, contributing to sustained neutrophil activation and liver inflammation. The study also shows that IL-8 is upregulated in sAH due to increased expression of IL-1β and TNF-α, as well as transcription factors like REL and FOS. Additionally, the expression of neutrophil chemokines such as CXCL8 (IL-8), CXCL6, and CXCL5 is elevated in sAH livers, with CXCL8 primarily expressed by neutrophils and CXCL6 by hepatocytes. These findings suggest that targeting IL-8⁺ neutrophils could be a promising therapeutic strategy for sAH by blocking IL-8 signaling through anti-IL-8 antibodies or CXCR1/2 antagonists. The study highlights the importance of neutrophil infiltration and IL-8 signaling in the pathogenesis of sAH, emphasizing the need for further research into these mechanisms.Alcohol-associated hepatitis (sAH) is a severe form of alcohol-related liver disease with high mortality and limited treatment options. A study identifies that IL-8⁺ neutrophils play a critical role in the progression from alcohol-associated cirrhosis (AC) to sAH. Using single-cell RNA sequencing, researchers found that sAH livers have significantly higher numbers of neutrophils compared to AC livers, with these neutrophils expressing high levels of IL-8. These IL-8⁺ neutrophils are associated with increased TNF-α, IFN-γ, and inflammatory pathways, contributing to sustained neutrophil activation and liver inflammation. The study also shows that IL-8 is upregulated in sAH due to increased expression of IL-1β and TNF-α, as well as transcription factors like REL and FOS. Additionally, the expression of neutrophil chemokines such as CXCL8 (IL-8), CXCL6, and CXCL5 is elevated in sAH livers, with CXCL8 primarily expressed by neutrophils and CXCL6 by hepatocytes. These findings suggest that targeting IL-8⁺ neutrophils could be a promising therapeutic strategy for sAH by blocking IL-8 signaling through anti-IL-8 antibodies or CXCR1/2 antagonists. The study highlights the importance of neutrophil infiltration and IL-8 signaling in the pathogenesis of sAH, emphasizing the need for further research into these mechanisms.