Alcohol-associated hepatitis: a neutrophile disease?

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 …