Alcohol-associated hepatitis (AH) is the acute deterioration of alcohol-related liver disease (ArLD) with rapid onset or worsening of jaundice, which, in severe cases, may transition to acute-on-chronic liver failure (ACLF) with extremely high short-term mortality, increasing with the number and severity of hepatic and extra-hepatic organ dysfunction. Systemic inflammation is a hallmark, driving acute decompensation (AD) towards ACLF. Diagnosis and treatment are insufficient and challenging, especially due to the complex, multifactorial and as yet not fully understood pathogenesis. In patients with AH, this inflammation is characterised by increased levels of circulating and hepatic neutrophils, which are essential immune cells responsible for pathogen defence. However, the exact role of neutrophils in AH remains controversial, with ongoing debate over whether their hyperactivation exacerbates liver damage or helps to resolve the disease. Current treatment for AH primarily relies on steroids, but their use is restricted in cases of bacterial infections. Consequently, there is a clinical need to better understand the mechanisms underlying AH and the associated organ dysfunction. Moreover, early detection and treatment of bacterial infections are critical to improve patient outcomes. These challenges, coupled with its rising prevalence in Germany and other Western countries, highlight a significant gap in patient care.1 Chronic alcohol consumption is associated with gut dysbiosis, leading to alterations in the composition of bacteria, viruses and fungi. Several bacterial metabolites were identified to foster liver disease progression. Among them, cytolysin, an endotoxin secreted by Enterococcus faecalis, is associated with higher hepatic inflammation and higher short-term mortality in patients with AH.2 …

中文翻译：

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酒精相关性肝炎：一种嗜中性粒细胞疾病？


酒精相关性肝炎 （AH） 是酒精相关性肝病 （ArLD） 的急性恶化，伴有黄疸的快速发作或恶化，在严重的情况下，可能会转变为慢加急性肝衰竭 （ACLF），短期死亡率极高，随着肝和肝外器官功能障碍的数量和严重程度而增加。全身炎症是一个标志，导致急性失代偿 （AD） 走向 ACLF。诊断和治疗不足且具有挑战性，特别是由于复杂、多因素且尚未完全了解的发病机制。在 AH 患者中，这种炎症的特征是循环和肝脏中性粒细胞水平升高，中性粒细胞是负责病原体防御的重要免疫细胞。然而，中性粒细胞在 AH 中的确切作用仍然存在争议，关于它们的过度激活是加剧肝损伤还是有助于解决疾病，一直存在争议。目前 AH 的治疗主要依赖于类固醇，但其使用仅限于细菌感染。因此，临床需要更好地了解 AH 和相关器官功能障碍的潜在机制。此外，细菌感染的早期检测和治疗对于改善患者预后至关重要。这些挑战，再加上它在德国和其他西方国家日益流行，凸显了患者护理方面的巨大差距。长期饮酒与肠道菌群失调有关，导致细菌、病毒和真菌的组成发生变化。已确定几种细菌代谢物可促进肝病进展。 其中，溶细胞素是粪肠球菌分泌的一种内毒素，与 AH 患者较高的肝脏炎症和较高的短期死亡率有关。2 …