Serum Metabolic Disturbances Associated with Acute-on-chronic Liver Failure in Patients with Underlying Alcoholic Liver Diseases

Abstract

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. 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.

Salbutamol Attenuates Diabetic Skeletal Muscle Atrophy by Reducing Oxidative Stress, Myostatin/GDF-8, and Pro-Inflammatory Cytokines in Rats

“…These findings suggest that impaired glucose metabolism and disrupted insulin regulation in diabetes indicate disturbances in fatty acid oxidation [ 68 , 69 ]. An elevated level of circulatory PTR (for oxidative markers) and HTR (for inflammatory markers) indicates that disease-induced oxidative stress and inflammation, and hyper-activation of the immune system led to predicated disease [ 53 , 70 ]. PTR and HTR assess the body’s capacity to convert phenylalanine to tyrosine and the histidine-to-tyrosine ratio.…”

“…Then, 3-hydroxy-butyrate (3HB), acetone, alanine, betaine, acetate, choline, citrate, dimethyl sulfone (DMS), creatine, dimethylamine (DMA), glutamine, glucose, glutamate, glycine, glycerol, isoleucine, isobutyrate (IsoB), leucine, lactate, phenylalanine, methanol, pyruvate, succinate, proline, serine, threonine, valine, tyrosine, histidine, and myoinositol. Following this, the metabolic profiles were utilized to estimate five key metabolic ratios, including the phenylalanine-to-tyrosine ratio (PTR), histidine-to-tyrosine ratio (HTR), and glutamate-to-glutamine ratio (EQR), as discussed in the preceding section [ 52 , 53 ].…”

Difference and clinical value of metabolites in plasma and feces of patients with alcohol-related liver cirrhosis

“…A previous study by Marchesini et al [ 30 ] suggested that the increase of plasma methionine in patients with cirrhosis could be attributed to the damage of liver cells and the decrease in methionine’s metabolic function. In addition, the NMR-based metabolomics analysis by Kumar et al [ 31 ] showed increased serum methionine in patients with acute-on-chronic liver failure. Moreover, our study found that plasma L-phenylalanine, L-tyrosine, and L-methionine were positively correlated with TBil and MDF, suggesting that these three amino acids may be related to the severity of diseases, and are designated as markers of disease progression in the blood.…”