Saha Rohini, Sharma Samriddhi, Mondal Antara, Sati Hem C, Khan Maroof A, Mahajan Sandeep, Datta Sudip, Acharya Pragyan
Department of Biochemistry, All India Institute of Medical Sciences, New Delhi, India.
National Centre for Cell Science, Pune, India.
J Clin Exp Hepatol. 2025 May-Jun;15(3):102491. doi: 10.1016/j.jceh.2024.102491. Epub 2024 Dec 23.
BACKGROUND/AIMS: Acute-on-chronic liver failure (ACLF) is a complication of cirrhosis associated with systemic inflammation and organ dysfunction. In ACLF, the development of acute kidney injury (AKI) is associated with poor outcomes. FABP1, NGAL, Cys C and IL-18 have been shown to correlate with ACLF severity and mortality. Hence, our study aimed to evaluate the association of these biomarkers with organ dysfunctions, particularly AKI, in an Indian ACLF patient cohort.
151 study participants including ACLF (n = 91; with AKI n = 63, no-AKI n = 28), non-liver AKI (n = 30) and healthy controls (n = 30) were recruited. Serum ELISA was performed for biomarker estimation. Data interpolation and graphical representation were performed using GraphPad Prism and statistical analyses performed using STATA 14.0.
FABP1 and Cys C levels were higher in ACLF-AKI patients compared to ACLF no-AKI (-value ≤ 0.0005). Serum Cys C levels were significantly increased in non-liver AKI compared to ACLF-AKI (-value ≤ 0.001). AUROC analysis showed better performance of Cys C (AUC 0.79; 95% CI (0.68-0.89)) compared to serum creatinine (AUC 0.71; 95% CI (0.61-0.82)) in discriminating AKI and no-AKI. Correlation analysis revealed positive correlations of FABP1 with creatinine and urea, Cys C with creatinine, urea and OF-Kidney, NGAL, and IL-18 with general markers of organ dysfunction. Plasma MTs) measured in a subset of ACLF patients were elevated in progression-to-AKI.
Our study showed that in an Indian population of ACLF patients with a high short-term mortality, serum Cys C and FABP1 were elevated in ACLF-AKI, however did not have predictive potential for ACLF-AKI. Cys C levels were significantly higher in non-liver AKI patients vs. ACLF-AKI and correlated with markers of kidney dysfunction whereas NGAL and IL-18 represented higher inflammation and total organ dysfunction. Hence, we conclude that these biomarkers were elevated in ACLF-AKI but did not have predictive potential for AKI in ACLF.
背景/目的：慢加急性肝衰竭（ACLF）是肝硬化的一种并发症，与全身炎症和器官功能障碍相关。在ACLF中，急性肾损伤（AKI）的发生与不良预后相关。已有研究表明，脂肪酸结合蛋白1（FABP1）、中性粒细胞明胶酶相关脂质运载蛋白（NGAL）、胱抑素C（Cys C）和白细胞介素-18（IL-18）与ACLF的严重程度和死亡率相关。因此，我们的研究旨在评估这些生物标志物与印度ACLF患者队列中器官功能障碍，尤其是AKI的相关性。
招募了151名研究参与者，包括ACLF患者（n = 91；其中AKI患者n = 63，无AKI患者n = 28）、非肝性AKI患者（n = 30）和健康对照者（n = 30）。采用血清酶联免疫吸附测定法（ELISA）进行生物标志物检测。使用GraphPad Prism软件进行数据插值和图形表示，并使用STATA 14.0软件进行统计分析。
与ACLF无AKI患者相比，ACLF-AKI患者的FABP1和Cys C水平更高（P值≤0.0005）。与ACLF-AKI患者相比，非肝性AKI患者的血清Cys C水平显著升高（P值≤0.001）。受试者工作特征曲线下面积（AUROC）分析显示，在区分AKI和无AKI方面，Cys C的表现优于血清肌酐（Cys C的AUC为0.79；95%置信区间（CI）为（0.68 - 0.89），血清肌酐 的AUC为0.71；95%CI为（0.61 - 0.82））。相关性分析显示，FABP1与肌酐和尿素呈正相关，Cys C与肌酐、尿素以及急性肾损伤（OF-Kidney）、NGAL和IL-18与器官功能障碍的一般标志物呈正相关。在一部分ACLF患者中检测到的血浆金属硫蛋白（MTs）在进展为AKI时升高。
我们的研究表明，在短期死亡率较高的印度ACLF患者人群中，ACLF-AKI患者的血清Cys C和FABP1升高，但对ACLF-AKI没有预测潜力。非肝性AKI患者的Cys C水平显著高于ACLF-AKI患者，且与肾功能障碍标志物相关，而NGAL和IL-18代表更高的炎症和全身器官功能障碍。因此，我们得出结论，这些生物标志物在ACLF-AKI中升高，但对ACLF中的AKI没有预测潜力。
