Serum metabolites detect the presence of advanced fibrosis in derivation and validation cohorts of patients with non-alcoholic fatty liver disease
Serum metabolites detect the presence of advanced fibrosis in derivation and validation cohorts of patients with non-alcoholic fatty liver disease
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DOI：
10.1136/gutjnl-2018-317584
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发表时间：
2019-10-01
期刊：
影响因子：
24.5
通讯作者：
Loomba, Rohit
中科院分区：
文献类型：
--
作者：
Caussy, Cyrielle;Ajmera, Veeral H.;Loomba, Rohit
目的非酒精性脂肪性肝病（NAFLD）的非侵入性和准确的疾病严重程度筛查诊断测试仍然是一个主要的未满足的需求。因此，我们的目的是研究血清代谢物的组合是否能准确预测晚期纤维化的存在。这是一项前瞻性衍生队列的横断面分析，包括156例活检证实的NAFLD患者和两个验证队列，其中(1)142例患者使用MRI弹性成像（MRE）评估，(2)59例活检证实的NAFLD患者使用非靶向血清代谢组谱分析。在衍生队列中，23名参与者（15%）患有晚期纤维化，经过假发现率调整后，分析的652种代谢物中有32种与晚期纤维化显著相关。在前10位代谢产物中，鉴定出8种脂质（5 α -雄酮-3-单硫酸酯、孕二醇-3-葡萄糖醛酸酯、硫酸雄酮、硫酸表雄酮、棕榈油酸酯、硫酸脱氢异雄酮、5 α -雄酮-3-二硫酸酯、糖胆酸酯）、1种氨基酸（牛磺酸）和1种碳水化合物（焦糖）。前10个代谢物组的受试者工作特征曲线下的联合面积（AUROC）高于FIB-4和NAFLD纤维化评分（NFS），用于检测晚期纤维化：分别为0.94 （95% CI 0.897 ~ 0.982）和0.78 (95% CI 0.674 ~ 0.891), p=0.002和0.84 (95% CI 0.724 ~ 0.929), p=0.017。在MRE或肝活检评估的独立验证队列中，前10个代谢物组的AUROC仍然很好：c统计量分别为0.94和0.84。结论：10种血清代谢物的组合在一个衍生品和两个独立验证队列中显示出出色的晚期纤维化检测能力，其诊断准确性高于fib -4指数和NFS。这项概念验证研究表明，一种非侵入性的基于血液的诊断测试可以为晚期纤维化的检测提供出色的性能特征。
Objective Non-invasive and accurate diagnostic tests for the screening of disease severity in non-alcoholic fatty liver disease (NAFLD) remain a major unmet need. Therefore, we aimed to examine if a combination of serum metabolites can accurately predict the presence of advanced fibrosis.Design This is a cross-sectional analysis of a prospective derivation cohort including 156 well-characterised patients with biopsy-proven NAFLD and two validation cohorts, including (1) 142 patients assessed using MRI elastography (MRE) and(2) 59 patients with biopsy-proven NAFLD with untargeted serum metabolome profiling.Results In the derivation cohort, 23 participants (15%) had advanced fibrosis and 32 of 652 analysed metabolites were significantly associated with advanced fibrosis after false-discovery rate adjustment. Among the top 10 metabolites, 8 lipids (5alpha-androstan-3beta monosulfate, pregnanediol-3-glucuronide, androsterone sulfate, epiandrosterone sulfate, palmitoleate, dehydroisoandrosterone sulfate, 5alpha-androstan-3beta disulfate, glycocholate), one amino acid (taurine) and one carbohydrate (fucose) were identified. The combined area under the receiver operating characteristic curve (AUROC) of the top 10 metabolite panel was higher than FIB-4 and NAFLD Fibrosis Score (NFS) for the detection of advanced fibrosis: 0.94 (95% CI 0.897 to 0.982) versus 0.78 (95% CI 0.674 to 0.891), p=0.002 and versus 0.84 (95% CI 0.724 to 0.929), p=0.017, respectively. The AUROC of the top 10 metabolite panel remained excellent in the independent validation cohorts assessed by MRE or liver biopsy: c-statistic of 0.94 and 0.84, respectively.Conclusion A combination of 10 serum metabolites demonstrated excellent discriminatory ability for the detection of advanced fibrosis in an derivation and two independent validation cohorts with greater diagnostic accuracy than the FIB-4-index and NFS. This proof-of-concept study demonstrates that a non-invasive blood-based diagnostic test can provide excellent performance characteristics for the detection of advanced fibrosis.