脆弱性是生理储备下降的临床表型，在肝硬化病人中是异质性健康结果的强力决定因素。目前仅有唯一一项针对肝硬化的脆弱性测评指标：肝脆弱指数（LFI），但该测试需要亲自进行，可能无法适用于临床场景。我们致力于探索血清/血浆蛋白生物标志物，以区分受肝硬化影响的病人中脆弱和强壮两类人群。研究对象包括140名等待肝移植的肝硬化成人，他们在门诊接受过LFI评估，并且有可用的血清/血浆样本。我们选择了70对病人，这些病人脆弱度水平相反（LFI > 4.4代表脆弱， LFI < 3.2代表强壮），并通过年龄、性别、病因、肝癌和MELDNa匹配。我们选取了与脆弱性有生物学相关的25种生物标志物，并送到单个实验室进行ELISA检测。条件逻辑回归用于检验生物标志物与脆弱性的关联。从25种检测的生物标志物中，我们发现了7种蛋白质在脆弱和强壮两类病人中表达不同。在这7种蛋白中，我们观察到了6种蛋白的左右差异：a）脆弱群体的生长分化因子-15（3682vs. 2249 pg / mL），白细胞介素-6（17.4vs. 6.4 pg / mL），肿瘤坏死因子-alpha受体1（2062vs. 1627 pg / mL），富含亮氨酸的α-2糖蛋白（44.0 vs. 38.6 ug / mL），肌肉分化信号分子（4066 vs. 6006 ng / mL）的中位数值高于强壮群体的中位数值；b）脆弱群体中α-2 Heremans-Schmid糖蛋白（0.11 vs. 0.13 mg / mL）和游离总睾酮（1.2 vs. 2.4 ng / mL）中位数值低于强壮群体。这些生物标志物反映了脆弱状态下多种生理紊乱，包括炎症、肌肉骨骼和内分泌代谢系统。这些数据为后续的确认性研究和发展一个基于实验室的肝硬化脆弱指数，从而改善其诊断和预后提供了基础。 版权所有©2023美国肝脏疾病研究协会。

Frailty, a clinical phenotype of decreased physiologic reserve, is a strong determinant of adverse health outcomes in patients with cirrhosis. The only cirrhosis-specific frailty metric is the Liver Frailty Index (LFI) which must be administered in person and may not be feasible for every clinical scenario. We sought to discover candidate serum/plasma protein biomarkers that could differentiate frail from robust patients with cirrhosis.Included were 140 adults with cirrhosis awaiting liver transplantation in the ambulatory setting with LFI assessments and available serum/plasma samples. We selected 70 pairs of patients on opposite ends of the frailty spectrum (LFI> 4.4 for frail and LFI<3.2 for robust) who were matched by age, sex, etiology, HCC, and MELDNa. Twenty-five biomarkers with biologically plausible associations with frailty were analyzed by ELISA by a single laboratory. Conditional logistic regression was used to examine their association with frailty. Of the 25 biomarkers analyzed, we identified 7 proteins that were differentially expressed between frail and robust. We observed differences in 6 of the 7 proteins in the expected direction: a) higher median values in frail versus robust with growth-differentiation factor-15 (3682 vs. 2249 pg/mL), interleukin-6 (17.4 vs. 6.4 pg/mL), tumor necrosis factor-alpha receptor 1 (2062 vs. 1627 pg/mL), leucine-rich alpha-2 glycoprotein (44.0 vs. 38.6 ug/mL), and myostatin (4066 vs. 6006 ng/mL), and b) lower median values in frail versus robust with alpha-2-Heremans-Schmid glycoprotein (0.11 vs. 0.13 mg/mL) and free total testosterone (1.2 vs. 2.4 ng/mL).These biomarkers represent inflammatory, musculoskeletal, and endocrine/metabolic systems, reflecting the multiple physiologic derangements observed in frailty. These data lay the foundation for confirmatory work and development of a laboratory frailty index for patients with cirrhosis to improve diagnosis and prognostication.Copyright © 2023 American Association for the Study of Liver Diseases.