Dasgupta Anushka, Jones Tiffanie K, Giannini Heather, Bennett Rachel, Emre Gulus, Ittner Caroline A G, Turner Alexandra, Esperanza Mika, Housel Kaitlyn, Miano Todd, Erlich Matthew, Anderson Brian J, Shashaty Michael G S, Meyer Nuala J, Reilly John P
College of Arts and Sciences, University of Pennsylvania, Philadelphia, PA, USA.
Division of Pulmonary, Allergy, and Critical Care, Perelman School of Medicine, University of Pennsylvania, 5042 Gates Building, 3400 Spruce Street, Philadelphia, PA, 19104, USA.
Crit Care. 2025 May 19;29(1):199. doi: 10.1186/s13054-025-05423-6.
The pre-existing diagnosis of cirrhosis is a complicating factor in the progression and prognosis of sepsis; however, the unique epidemiology, sepsis characteristics, and underlying mechanisms of immune dysregulation in sepsis among patients with cirrhosis remain incompletely understood. Our primary objective was to identify clinical outcomes and biological characteristics that differ between patients with and without cirrhosis among critically ill patients with sepsis.
We analyzed data from a prospective cohort of critically ill patients presenting to single center with sepsis. Subjects were followed for 6 days for the development of acute respiratory distress syndrome (ARDS) and acute kidney injury (AKI), and 30 days for mortality. Inflammatory, endothelial, and coagulopathic proteins were measured in plasma collected at ICU admission in a subset of patients. We determined associations of cirrhosis with outcomes using multivariable logistic regression adjusting for pre-specified confounders. We tested differences in plasma protein levels by cirrhosis diagnosis using the Wilcoxon Rank-sum test.
We enrolled 2962 subjects, 371 (13%) of whom had a pre-existing diagnosis of cirrhosis. Patients with cirrhosis had higher severity of illness scores, were more likely to have an abdominal source of sepsis, and had more significant clinically measured coagulation abnormalities relative to patients without cirrhosis. In multivariate analysis, cirrhosis was associated with higher AKI risk (adjusted OR 1.65; 95% CI 1.21 to 2.26; P = 0.002), and 30-day mortality (adjusted OR 1.38; 95% CI 1.05 to 1.82; P = 0.022). There was no significant difference in risk for ARDS (adjusted OR 1.02; 95% CI 0.69 to 1.50; P = 0.92). Cirrhosis was associated with higher plasma levels of angiopoietin-2 (P < 0.001), von Willebrand factor (P < 0.001), and soluble thrombomodulin (P < 0.001), as well as lower levels of interleukin (IL)-10 (P < 0.001), IL-1β (P = 0.008), and IL-1RA (P = 0.036). There were no significant differences in levels of IL-6 (P = 0.30).
We identified associations between pre-existing cirrhosis and endothelial injury, AKI, and mortality in sepsis. Patients with pre-existing cirrhosis who develop sepsis may display a unique phenotype of endothelial dysfunction that requires unique targeted approaches.
肝硬化的既往诊断是脓毒症进展和预后的一个复杂因素；然而，肝硬化患者脓毒症的独特流行病学、脓毒症特征及免疫失调的潜在机制仍未完全明确。我们的主要目的是确定脓毒症重症患者中肝硬化患者与非肝硬化患者之间存在差异的临床结局和生物学特征。
我们分析了一家单中心收治的脓毒症重症患者前瞻性队列的数据。对受试者随访6天观察急性呼吸窘迫综合征（ARDS）和急性肾损伤（AKI）的发生情况，随访30天观察死亡率。在一部分患者入重症监护病房（ICU）时采集的血浆中检测炎症、内皮和凝血相关蛋白。我们使用多变量逻辑回归对预先指定的混杂因素进行调整，以确定肝硬化与结局之间的关联。我们使用Wilcoxon秩和检验来检测肝硬化诊断对血浆蛋白水平的差异。
我们纳入了2962名受试者，其中371名（13%）有肝硬化的既往诊断。与非肝硬化患者相比，肝硬化患者的疾病严重程度评分更高，更有可能有腹部脓毒症来源，且临床测量的凝血异常更显著。在多变量分析中，肝硬化与更高的AKI风险（校正比值比1.65；95%置信区间1.21至2.26；P = 0.002）和30天死亡率（校正比值比1.38；95%置信区间1.05至1.82；P = 0.022）相关。ARDS风险无显著差异（校正比值比1.02；95%置信区间0.69至1.50；P = 0.92）。肝硬化与更高的血浆血管生成素-2水平（P < 0.001）、血管性血友病因子水平（P < 0.001）和可溶性血栓调节蛋白水平（P < 0.001）相关，同时与更低的白细胞介素（IL）-10水平（P < 0.001）、IL-1β水平（P = 0.008）和IL-1受体拮抗剂水平（P = 0.036）相关。IL-6水平无显著差异（P = 0.30）。
我们确定了既往肝硬化与脓毒症中的内皮损伤、AKI和死亡率之间的关联。发生脓毒症的既往肝硬化患者可能表现出独特的内皮功能障碍表型，需要采取独特的针对性方法。
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