肝病患者肠道微生物和脂类成分产生的血清代谢物水平与急

StephenW

Serum Levels of Metabolites Produced by Intestinal Microbes and Lipid Moieties Independently Associated With Acute-on-Chronic Liver Failure and Death in Patients With Cirrhosis

    Jasmohan S. Bajaj
    K. Rajender Reddy
    Jacqueline G. O’Leary
    Masoumeh Sikaroodi
    Guadalupe Garcia-Tsao
    Patrick M. Gillevet
    Show all authors

Published:July 17, 2020DOI:https://doi.org/10.1053/j.gastro.2020.07.019
PlumX Metrics

    Graphical abstract
    Keywords
    References
    Supplementary References
    Article Info

Background & Aims
Inpatients with cirrhosis have high rates of acute-on-chronic failure (ACLF) development and high mortality within 30 days of admission to the hospital. Better biomarkers are needed to predict these outcomes. We performed metabolomic analyses of serum samples from patients with cirrhosis at multiple centers to determine whether metabolite profiles might identify patients at high risk for ACLF and death.
Methods
We performed metabolomic analyses, using liquid chromatography, of serum samples collected at time of admission to 12 North American tertiary hepatology centers from 602 patients in the North American Consortium for the Study of End-Stage Liver Disease sites from 2015 through 2017 (mean age, 56 years; 61% men; mean model for end-stage liver disease score, 19.5). We performed analysis of covariance, adjusted for model for end-stage liver disease at time of hospital admission, serum levels of albumin and sodium, and white blood cell count, to identify metabolites that differed between patients who did vs did not develop ACLF and patients who did vs did not die during hospitalization and within 30 days. We performed random forest analysis to identify specific metabolite(s) that were associated with outcomes and area under the curve (AUC) analyses to analyze them in context of clinical parameters. We analyzed microbiomes of stool samples collected from 133 patients collected at the same time and examined associations with serum metabolites.
Results
Of the 602 patients analyzed, 88 developed ACLF (15%), 43 died in the hospital (7%), and 72 died within 30 days (12%). Increased levels of compounds of microbial origin (aromatic compounds, secondary or sulfated bile acids, and benzoate) and estrogen metabolites, as well as decreased levels of phospholipids, were associated with development of ACLF, inpatient, and 30-day mortality and were also associated with fecal microbiomes. Random forest analysis and logistic regression showed that levels of specific microbially produced metabolites identified patients who developed ACLF with an AUC of 0.84 (95% confidence interval [CI] 0.78–0.88; P = .001), patients who died while in the hospital with an AUC of 0.81 (95% CI 0.74–0.85; P = .002), and patients who died within 30 days with an AUC of 0.77 (95% CI 0.73–0.81; P = .02). The metabolites were significantly additive to clinical parameters for predicting these outcomes. Metabolites associated with outcomes were also correlated with microbiomes of stool samples.
Conclusions
In an analysis of serum metabolites and fecal microbiomes of patients hospitalized with cirrhosis at multiple centers, we associated metabolites of microbial origin and lipid moieties with development of ACLF and death as an inpatient or within 30 days, after controlling for clinical features.

StephenW

肝病患者肠道微生物和脂类成分产生的血清代谢物水平与急性肝功能衰竭和死亡独立相关

    Jasmohan S.Bajaj
    K·拉杰德·雷迪
    杰奎琳·G·奥莱里
    Masoumeh Sikaroodi
    瓜达卢佩·加西亚·曹
    帕特里克·吉列维
    显示所有作者

发布时间：2020年7月17日DOI：https：//doi.org/10.1053/j.gastro.2020.07.019
PlumX指标

    图形概要
    关键词
    参考文献
    补充参考
    文章信息

背景与目标
肝硬化住院患者入院后30天内，急性慢性衰竭（ACLF）发生率较高，死亡率很高。需要更好的生物标志物来预测这些结果。我们在多个中心对肝硬化患者的血清样本进行了代谢组学分析，以确定代谢物谱是否可以识别出患有ACLF和死亡的高风险患者。
方法
我们使用液相色谱法对从2015年至2017年（研究对象为平均年龄，12岁以下）的北美结直肠疾病研究站点联盟中的602名患者进入12个北美三级肝病中心收治的血清样本进行了代谢组学分析56岁；男性占61％；终末期肝病平均模型得分：19.5）。我们进行了协方差分析，并针对入院时的终末期肝病模型，白蛋白和钠的血清水平以及白细胞计数进行了调整，以识别出患有或未患有ACLF的患者与患者之间差异的代谢产物谁vs谁在住院期间和30天内没有死亡。我们进行了随机森林分析，以鉴定与代谢物和曲线下面积（AUC）分析相关的特定代谢物，并根据临床参数对其进行分析。我们分析了从同时收集的133名患者中收集的粪便样本的微生物组，并检查了与血清代谢物的关联。
结果
在分析的602例患者中，有88例发展为ACLF（15％），其中43例在医院死亡（7％），72例在30天内死亡（12％）。微生物来源的化合物（芳香族化合物，仲或硫酸化胆汁酸和苯甲酸酯）和雌激素代谢物水平的升高以及磷脂水平的降低与ACLF的发生，住院和30天死亡率有关，并且也与粪便微生物群。随机森林分析和逻辑回归分析表明，特定微生物产生的代谢产物水平可确定患有ACLF且AUC为0.84（95％置信区间[CI] 0.78–0.88； P = .001）的患者，在医院死亡的患者。 AUC为0.81（95％CI 0.74–0.85; P = .002），而在30天内死亡的患者的AUC为0.77（95％CI 0.73-0.81; P = .02）。代谢物是临床参数的重要添加剂，可预测这些结果。与结果相关的代谢产物也与粪便样本的微生物组相关。
结论
在对多中心肝硬化住院患者的血清代谢产物和粪便微生物群进行分析后，我们将微生物来源和脂质部分的代谢产物与住院患者或控制临床特征后30天之内的住院或30天内ACLF的发生和死亡相关联。