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Serum metabolic disturbances associated with acute-on-chronic liver failure in patients with underlying alcoholic liver diseases: An elaborative NMR-based metabolomics study
Umesh Kumar1, Supriya Sharma2, Manjunath Durgappa3, Nikhil Gupta4, Ritu Raj4, Alok Kumar3, Prabhat Narayan Sharma3, VP Krishna3, R Venkatesh Kumar2, Anupam Guleria4, Vivek Anand Saraswat3, Gaurav Pande3, Dinesh Kumar4
1 Department of Clinical Metabolomics, 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
2 Department of Gastrosurgery, Sanjay Gandhi Postgraduate Institute of Medical Sciences (SGPGIMS), Lucknow, Uttar Pradesh, India
3 Department of Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences (SGPGIMS), Lucknow, Uttar Pradesh, India
4 Department of Clinical Metabolomics, Centre of Biomedical Research (CBMR), Sanjay Gandhi Postgraduate Institute of Medical Sciences (SGPGIMS), Lucknow, Uttar Pradesh, India
Correspondence Address:
Dinesh Kumar,
Centre of Biomedical Research (CBMR), SGPGIMS Campus, Lucknow 226014, Uttar Pradesh, ORCID:0000-0001-8079-6739
India
Gaurav Pande,
Department of Gastroeneterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences (SGPGIMS), Lucknow 226014, Uttar Pradesh
India
 Source of Support: None, Conflict of Interest: None DOI: 10.4103/JPBS.JPBS_333_20
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Objectives: 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. Materials and Methods: 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. Results: 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. The markedly decreased serum levels of branched-chain-amino-acids (valine, leucine, and isoleucine) and elevated levels of trimethylamine N-oxide (TMAO) and methionine were found significantly correlated with clinical scores used to assess the severity of hepatic impairment 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. Conclusion: 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. |
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