关键词: Biomarkers CHE CHE, covert hepatic encephalopathy Cognitive deficit Complications of cirrhosis GFAP GFAP, glial fibrillary acidic protein HE HE, hepatic encephalopathy HE2, grade 2 hepatic encephalopathy MELD, model for end-stage liver disease MHE, minimal hepatic encephalopathy OHE, overt hepatic encephalopathy OR, odds ratio PHES, psychometric hepatic encephalopathy score Psychometric hepatic encephalopathy score ROC, receiver operating characteristic SiMoA, single-molecule array WBC, white blood cell sGFAP, serum glial fibrillary acidic protein

来  源:   DOI:10.1016/j.jhepr.2023.100671   PDF(Pubmed)

Abstract:
UNASSIGNED: Blood biomarkers facilitating the diagnosis of covert hepatic encephalopathy (CHE) in patients with cirrhosis are lacking. Astrocyte swelling is a major component of hepatic encephalopathy. Thus, we hypothesised that glial fibrillary acidic protein (GFAP), the major intermediate filament of astrocytes, might facilitate early diagnosis and management. This study aimed to investigate the utility of serum GFAP (sGFAP) levels as a biomarker of CHE.
UNASSIGNED: In this bicentric study, 135 patients with cirrhosis, 21 patients with ongoing harmful alcohol use and cirrhosis, and 15 healthy controls were recruited. CHE was diagnosed using psychometric hepatic encephalopathy score. sGFAP levels were measured using a highly sensitive single-molecule array (SiMoA) immunoassay.
UNASSIGNED: In total, 50 (37%) people presented with CHE at study inclusion. Participants with CHE displayed significantly higher sGFAP levels than those without CHE (median sGFAP, 163 pg/ml [IQR 136; 268] vs. 106 pg/ml [IQR 75; 153]; p <0.001) or healthy controls (p <0.001). sGFAP correlated with results in psychometric hepatic encephalopathy score (Spearman\'s ρ = -0.326, p <0.001), model for end-stage liver disease score (Spearman\'s ρ = 0.253, p = 0.003), ammonia (Spearman\'s ρ = 0.453, p = 0.002), and IL-6 serum levels (Spearman\'s ρ = 0.323, p = 0.006). Additionally, sGFAP levels were independently associated with the presence of CHE in multivariable logistic regression analysis (odds ratio 1.009; 95% CI 1.004-1.015; p <0.001). sGFAP levels did not differ between patients with alcohol-related cirrhosis vs. patients with non-alcohol-related cirrhosis or between patients with ongoing alcohol use vs. patients with discontinued alcohol use.Conclusions: sGFAP levels are associated with CHE in patients with cirrhosis. These results suggest that astrocyte injury may already occur in patients with cirrhosis and subclinical cognitive deficits and that sGFAP could be explored as a novel biomarker.
UNASSIGNED: Blood biomarkers facilitating the diagnosis of covert hepatic encephalopathy (CHE) in patients with cirrhosis are lacking. In this study, we were able to demonstrate that sGFAP levels are associated with CHE in patients with cirrhosis. These results suggest that astrocyte injury may already occur in patients with cirrhosis and subclinical cognitive deficits and that sGFAP could be explored as a novel biomarker.
摘要:
未经证实:缺乏促进肝硬化患者隐性肝性脑病(CHE)诊断的血液生物标志物。星形胶质细胞肿胀是肝性脑病的主要组成部分。因此,我们假设胶质纤维酸性蛋白(GFAP),星形胶质细胞的主要中间细丝,可能有助于早期诊断和管理。本研究旨在探讨血清GFAP(sGFAP)水平作为CHE生物标志物的实用性。
未经评估:在这项双中心研究中,135例肝硬化患者,21名患有持续有害饮酒和肝硬化的患者,招募了15名健康对照。使用心理测量学肝性脑病评分诊断CHE。使用高度敏感的单分子阵列(SiMoA)免疫测定来测量sGFAP水平。
未经批准:总共,50人(37%)在纳入研究时出现CHE。有CHE的参与者显示sGFAP水平显著高于没有CHE的参与者(sGFAP中位数,163pg/ml[IQR136;268]vs.106pg/ml[IQR75;153];p<0.001)或健康对照(p<0.001)。sGFAP与心理测量学肝性脑病评分结果相关(Spearman’sρ=-0.326,p<0.001),终末期肝病评分模型(Spearman’sρ=0.253,p=0.003),氨(斯皮尔曼的ρ=0.453,p=0.002),和IL-6血清水平(斯皮尔曼ρ=0.323,p=0.006)。此外,在多变量逻辑回归分析中,sGFAP水平与CHE的存在独立相关(比值比1.009;95%CI1.004-1.015;p<0.001)。酒精相关性肝硬化患者的sGFAP水平与非酒精相关性肝硬化患者或持续饮酒患者与停止饮酒的患者。结论:sGFAP水平与肝硬化患者CHE相关。这些结果表明,星形胶质细胞损伤可能已经发生在肝硬化和亚临床认知缺陷的患者中,并且sGFAP可以作为一种新的生物标志物进行探索。
未经证实:缺乏促进肝硬化患者隐性肝性脑病(CHE)诊断的血液生物标志物。在这项研究中,我们能够证明sGFAP水平与肝硬化患者的CHE相关.这些结果表明,星形胶质细胞损伤可能已经发生在肝硬化和亚临床认知缺陷的患者中,并且sGFAP可以作为一种新的生物标志物进行探索。
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