Kumar Umesh, Sharma Supriya, Durgappa Manjunath, Gupta Nikhil, Raj Ritu, Kumar Alok, Sharma Prabhat N, Krishna V P, Kumar R Venkatesh, Guleria Anupam, Saraswat Vivek A, Pande Gaurav, Kumar Dinesh
Centre of Biomedical Research (CBMR), Sanjay Gandhi Postgraduate Institute of Medical Sciences (SGPGIMS), Lucknow, Uttar Pradesh, India.
Department of Zoology, Babasaheb Bhimrao Ambedkar University (BBAU), Lucknow, Uttar Pradesh, India.
J Pharm Bioallied Sci. 2021 Apr-Jun;13(2):276-282. doi: 10.4103/JPBS.JPBS_333_20. Epub 2020 Dec 16.
Acute-on-chronic liver failure (ACLF), which develops in patients with underlying alcoholic liver disease (ALD), is characterized by acute deterioration of liver function and organ failures are secondary to that. The clear understanding of metabolic pathways perturbed in ALD-ACLF patients can greatly decrease the mortality and morbidity of patients through predicting outcome, guiding treatment, and monitoring response to treatment. The purpose of this study was to investigate the metabolic disturbances associated with ACLF using nuclear magnetic resonance (NMR)-based serum metabolomics approach and further to assess if the serum metabolic alterations are affected by the severity of hepatic impairment.
The serum-metabolic profiles of 40 ALD-ACLF patients were compared to those of 49 age and sex-matched normal-control (NC) subjects making composite use of both multivariate and univariate statistical tests.
Compared to NC, the sera of ACLF patients were characterized by significantly decreased serum levels of several amino acids (except methionine and tyrosine), lipid, and membrane metabolites suggesting a kind of nutritional deficiency and disturbed metabolic homeostasis in ACLF. Twelve serum metabolic entities (including BCAA, histidine, alanine, threonine, and glutamine) were found with AUROC (i.e., area under ROC curve) value >0.9 suggesting their potential in clinical diagnosis and surveillance.
Overall, the study revealed important metabolic changes underlying the pathophysiology of ACLF and those related to disease progression would add value to standard clinical scores of severity to predict outcome and may serve as surrogate endpoints for evaluating treatment response.
慢性酒精性肝病（ALD）患者发生的慢加急性肝衰竭（ACLF），其特征为肝功能急性恶化，器官功能衰竭继发于此。清楚了解ALD-ACLF患者中受干扰的代谢途径，可通过预测预后、指导治疗和监测治疗反应，极大降低患者的死亡率和发病率。本研究的目的是使用基于核磁共振（NMR）的血清代谢组学方法研究与ACLF相关的代谢紊乱，并进一步评估血清代谢改变是否受肝功能损害严重程度的影响。
综合运用多变量和单变量统计检验，将40例ALD-ACLF患者的血清代谢谱与49例年龄和性别匹配的正常对照（NC）受试者的血清代谢谱进行比较。
与NC相比，ACLF患者血清中几种氨基酸（蛋氨酸和酪氨酸除外）、脂质和膜代谢物的水平显著降低，提示ACLF存在某种营养缺乏和代谢稳态紊乱。发现12种血清代谢物（包括支链氨基酸、组氨酸、丙氨酸、苏氨酸和谷氨酰胺）的ROC曲线下面积（AUROC）值>0.9，表明它们在临床诊断和监测中的潜力。
总体而言，该研究揭示了ACLF病理生理学背后的重要代谢变化，与疾病进展相关的变化将为预测预后的标准临床严重程度评分增加价值，并可作为评估治疗反应的替代终点。
