Patient Plasma‐Induced Neutrophil Dysfunction Is Associated With Infection Risk and Mortality in Patients With Acute Decompensation of Cirrhosis
作者:Supachaya Sriphoosanaphan, Jane Macnaughtan, Haw Lu, Rohit Sawhney, Qianwen Zhao, Su Lin, Rocío Gallego‐Durán, Emmanuel Wey, Nathan Davies, Rajeshwar P. Mookerjee, Rajiv Jalan · 发表于:Alimentary Pharmacology & Therapeutics · 年份:2025 · DOI:10.1111/apt.70480 · 被引用次数:2 · 研究领域:Liver Disease and Transplantation、Sepsis Diagnosis and Treatment、Immune Response and Inflammation
BACKGROUND AND AIMS: Bacterial infection is a major cause of morbidity and mortality in patients with acute decompensation (AD) of cirrhosis. This study aimed to investigate patient plasma-induced dysfunction of healthy neutrophils (PIND) as a predictor of subsequent infection and mortality in patients with AD. METHODS: One hundred sixty AD patients (117 AD-NoACLF and 43 AD-ACLF), with a predominantly alcohol-related liver disease, were prospectively recruited. Plasma from 21 healthy controls and 74 patients with stable compensated cirrhosis was used as controls. Patient plasma was co-incubated with neutrophils from healthy donors to assess neutrophil function, including reactive oxygen species (ROS) production and phagocytic capacity, and CD62L surface expression. RESULTS: Plasma from AD patients induced a primed state in healthy neutrophils, characterised by increased constitutive and N-formyl-Met-Leu-Phe (fMLP)-induced ROS production. However, effector functions were impaired, with significantly reduced phorbol 12-myristate 13-acetate (PMA)-induced ROS production, phagocytic capacity and CD62L expression. Escherichia coli- induced ROS production predicted subsequent infection in the total AD and AD-NoACLF cohorts (p = 0.043 and p = 0.013, respectively), while PMA-induced ROS production predicted 90-day mortality in the AD-NoACLF group (p = 0.041). None of the neutrophil function assays were predictive of clinical outcomes in AD-ACLF patients. CONCLUSIONS: Plasma from patie...