Kulkarni Anand V, Sharma Mithun, Kumar Pramod, Simhadri Venu, Sowmya Tirumalige R, Mitnala Sasikala, Nageshwar Reddy Duvvuru, Nagaraja Rao Padaki
Department of Hepatology, Asian Institute of Gastroenterology, Hyderabad, India.
Department of Research, Asian Healthcare Foundation, Hyderabad, India.
J Clin Exp Hepatol. 2021 Mar-Apr;11(2):201-208. doi: 10.1016/j.jceh.2020.07.010. Epub 2020 Jul 28.
Alcohol is the leading cause of acute-on-chronic liver failure (ACLF). Several severity scores predict the outcome of ACLF. However, there is a lack of simple biomarkers in predicting the outcome of these sick patients. Fatty acid-binding proteins (FABPs) are small cytosolic proteins that play a major role in lipid metabolism, energy homeostasis, and inflammation, but, have not been investigated in alcohol-induced ACLF (A-ACLF).
The primary objective was to assess the correlation between serum adipocyte-FABP (A-FABP) and liver-FABP (L-FABP) levels on mortality at day 90. Secondary objectives were to compare the levels between controls and A-ACLF, correlate L-FABP, and A-FABP levels on the development of organ failure/sepsis at day 90.
In this prospective observational pilot study, we included patients with A-ACLF and age-matched healthy controls. FABP's were analyzed by enzyme-linked immunosorbent assay method. The patients were followed up for 90 days.
Twenty-five patients with A-ACLF (mean age: 40years; mean model for end-stage liver disease NA: 29.8; median Modified Maddrey's discriminant function [mDF]: 95) and 12 controls (mean age: 36.83yrs) were included in the study. A-FABP and L-FABP levels were significantly high in patients with A-ACLF than controls. Forty-four percent of patients with A-ACLF developed sepsis, 48% developed organ failure, and 44% expired by day 90. On multivariate Cox regression analysis, A-FABP (hazard ratio [HR]: 1.27 1.08-1.5; = 0.003), Asian Pacific Association for the Study of Liver ACLF research consortium score HR 3.31.15-9.54; = 0.02, L-FABP HR 0.69 0.52-0.91; = 0.009 and serum protein levels HR 0.03 0.003-0.36; = 0.005 predicted mortality. A-FABP 1.17 1.07-1.29; = 0.001, and serum bilirubin 1.05 0.99-1.12; = 0.06 predicted development of organ failure and only mDF HR 1.04 1.01-1.07; = 0.009 predicted the development of sepsis on multivariate analysis. Fifteen patients received steroid therapy, of which 13.34% were nonresponders.
In a selected group of patients with A-ACLF, A-FABP is highly sensitive at predicting mortality and outcome. If validated in a large, diverse sample, A-FABP can be used as a simple biomarker for prognostication in A-ACLF.
酒精是急性慢性肝衰竭（ACLF）的主要病因。有几种严重程度评分可预测ACLF的预后。然而，在预测这些患病患者的预后方面缺乏简单的生物标志物。脂肪酸结合蛋白（FABP）是一类小的胞质蛋白，在脂质代谢、能量稳态和炎症中起主要作用，但尚未在酒精性ACLF（A-ACLF）中进行研究。
主要目的是评估血清脂肪细胞FABP（A-FABP）和肝脏FABP（L-FABP）水平与90天时死亡率之间的相关性。次要目的是比较对照组和A-ACLF患者之间的水平，将L-FABP和A-FABP水平与90天时器官衰竭/脓毒症的发生情况相关联。
在这项前瞻性观察性试点研究中，我们纳入了A-ACLF患者和年龄匹配的健康对照。通过酶联免疫吸附测定法分析FABP。对患者进行90天的随访。
本研究纳入了25例A-ACLF患者（平均年龄：40岁；平均终末期肝病模型评分[NA]：29.8；改良Maddrey判别函数[mDF]中位数：95）和12例对照（平均年龄：36.83岁）。A-ACLF患者的A-FABP和L-FABP水平显著高于对照组。44%的A-ACLF患者发生脓毒症，48%发生器官衰竭，44%在90天时死亡。多因素Cox回归分析显示，A-FABP（风险比[HR]：1.27，95%置信区间[CI]：1.08 - 1.5；P = 0.003）、亚太肝脏研究协会ACLF研究联盟评分（HR：3.31，95%CI：1.15 - 9.54；P = 0.02）、L-FABP（HR：0.69，95%CI：0.52 - 0.91；P = 0.009）和血清蛋白水平（HR：0.03，95%CI：0.003 - 0.36；P = 0.005）可预测死亡率。A-FABP（HR：1.17，95%CI：1.07 - 1.29；P = 0.001）和血清胆红素（HR：1.05，95%CI：0.99 - 1.12；P = 0.06）可预测器官衰竭的发生，多因素分析中只有mDF（HR：1.04，95%CI：1.01 - 1.07；P = 0.009）可预测脓毒症的发生。15例患者接受了类固醇治疗，其中13.34%无反应。
在一组选定的A-ACLF患者中，A-FABP在预测死亡率和预后方面高度敏感。如果在大量、多样化的样本中得到验证，A-FABP可作为A-ACLF预后评估的简单生物标志物。
