Journal of Hepatology ( IF 26.8 ) Pub Date : 2021-09-13 , DOI: 10.1016/j.jhep.2021.08.031 Adrià Juanola 1 , Isabel Graupera 2 , Chiara Elia 3 , Salvatore Piano 4 , Cristina Solé 5 , Marta Carol 2 , Martina Pérez-Guasch 1 , Octavi Bassegoda 1 , Laia Escudé 1 , Ana-Belén Rubio 1 , Marta Cervera 1 , Laura Napoleone 1 , Emma Avitabile 1 , Ann T Ma 1 , Núria Fabrellas 6 , Elisa Pose 1 , Manuel Morales-Ruiz 7 , Wladimiro Jiménez 8 , Ferran Torres 9 , Gonzalo Crespo 1 , Elsa Solà 2 , Pere Ginès 2
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Background & Aims
Decompensated cirrhosis (DC) is associated with high mortality, mainly owing to the development of acute-on-chronic liver failure (ACLF). Identifying the patients with DC who are at high risk of mortality and ACLF development is an unmet clinical need. Liver fatty acid-binding protein (L-FABP) is expressed in several organs and correlates with liver and systemic inflammation. Herein, we aimed to assess the prognostic value of L-FABP in patients with DC.
Methods
A prospective series of 444 patients hospitalized for DC was divided into 2 cohorts: study cohort (305 patients) and validation cohort (139 patients). L-FABP was measured in urine and plasma samples collected at admission. Neutrophil gelatinase-associated lipocalin (NGAL) was also measured in urine samples for comparison.
Results
Urine but not plasma L-FABP correlated with 3-month survival on univariate analysis. On multivariate analysis, urine L-FABP and model for end-stage liver disease (MELD)-Na were the only independent predictors of prognosis. Urine L-FABP levels were higher in patients with ACLF than in those without and also predicted the development of ACLF, together with MELD-Na, during follow-up. In patients with ACLF, urine L-FABP correlated with liver, coagulation, and circulatory failure. Urine L-FABP levels were also increased in patients with acute kidney injury, particularly in those with acute tubular necrosis. The ability of urinary L-FABP to predict survival and ACLF development was confirmed in the validation cohort. Urine NGAL predicted outcome on univariate but not multivariate analysis.
Conclusions
Urinary L-FABP levels are independently associated with the 3-month clinical course in patients with DC, in terms of mortality and ACLF development. Urinary L-FABP is a promising prognostic biomarker for patients with DC.
Lay summary
Increased levels of liver fatty acid-binding protein (L-FABP), a protein related to lipid metabolism, have been associated with liver-related diseases. The present study analyzed urinary L-FABP levels in 2 independent groups of patients with decompensated cirrhosis and showed that higher urinary L-FABP levels correlated with increased mortality and risk of acute-on-chronic liver failure development. Therefore, urinary L-FABP levels could be useful as a new tool to predict complications in patients with decompensated cirrhosis.
中文翻译：
尿 L-FABP 是失代偿期肝硬化患者 ACLF 和死亡率的有希望的预后生物标志物
背景与目标
失代偿期肝硬化 (DC) 与高死亡率相关，主要是由于慢加急性肝衰竭 (ACLF) 的发展。识别具有高死亡率和 ACLF 发展风险的 DC 患者是一个未满足的临床需求。肝脏脂肪酸结合蛋白 (L-FABP) 在多个器官中表达，并与肝脏和全身炎症相关。在此，我们旨在评估 L-FABP 在 DC 患者中的预后价值。
方法
444 名因 DC 住院的患者的前瞻性系列分为 2 个队列：研究队列（305 名患者）和验证队列（139 名患者）。在入院时收集的尿液和血浆样本中测量 L-FABP。还在尿液样本中测量了中性粒细胞明胶酶相关载脂蛋白 (NGAL) 以进行比较。
结果
在单变量分析中，尿液而非血浆 L-FABP 与 3 个月生存率相关。在多变量分析中，尿 L-FABP 和终末期肝病模型 (MELD)-Na 是预后的唯一独立预测因子。ACLF 患者的尿 L-FABP 水平高于无 ACLF 患者，并且在随访期间与 MELD-Na 一起预测了 ACLF 的发展。在 ACLF 患者中，尿液 L-FABP 与肝脏、凝血和循环衰竭相关。急性肾损伤患者的尿 L-FABP 水平也升高，尤其是急性肾小管坏死患者。在验证队列中证实了尿 L-FABP 预测存活和 ACLF 发展的能力。尿液 NGAL 预测单变量而非多变量分析的结果。
结论
就死亡率和 ACLF 发展而言，尿 L-FABP 水平与 DC 患者的 3 个月临床过程独立相关。尿 L-FABP 是 DC 患者有前途的预后生物标志物。
总结
肝脏脂肪酸结合蛋白 (L-FABP) 水平升高，这是一种与脂质代谢相关的蛋白质，与肝脏相关疾病有关。本研究分析了 2 组独立的失代偿期肝硬化患者的尿 L-FABP 水平，结果表明，较高的尿 L-FABP 水平与死亡率和慢性加急性肝衰竭发展风险增加相关。因此，尿 L-FABP 水平可作为预测失代偿期肝硬化患者并发症的新工具。
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