Association of Metabolomic Change and Treatment Response in Patients with Non-Alcoholic Fatty Liver Disease

Abstract

Non-alcoholic fatty liver disease (NAFLD) is the major cause of chronic liver disease, yet cost-effective and non-invasive diagnostic tools to monitor the severity of the disease are lacking. We aimed to investigate the metabolomic changes in NAFLD associated with therapeutic responses. It was conducted in 63 patients with NAFLD who received either ezetimibe plus rosuvastatin or rosuvastatin monotherapy. The treatment response was determined by MRI performed at baseline and week 24. The metabolites were measured at baseline and week 12. In the combination group, a relative decrease in xanthine was associated with a good response to liver fat decrease, while a relative increase in choline was associated with a good response to liver stiffness. In the monotherapy group, the relative decreases in triglyceride (TG) 20:5_36:2, TG 18:1_38:6, acetylcarnitine (C2), fatty acid (FA) 18:2, FA 18:1, and docosahexaenoic acid were associated with a decrease in liver fat, while hexosylceramide (d18:2/16:0) and hippuric acid were associated with a decrease in liver stiffness. Models using the metabolite changes showed an AUC of >0.75 in receiver operating curve analysis for predicting an improvement in liver fat and stiffness. This approach revealed the physiological impact of drugs, suggesting the mechanism underlying the development of this disease.

Hepatoprotective efficacy and interventional mechanism of the panaxadiol saponin component in high-fat diet-induced NAFLD mice

“…However, in patients with hyperlipidemia, the concentrations of PA and OA were increased in different degrees, resulting in the accumulation of a large amount of TG in hepatocytes and accelerating the progression of fatty liver disease. 66 In vitro , PA or OA as inducers are often used to mimic hepatocyte injury caused by excessive fatty acids. However, some studies have shown that unsaturated OA is less toxic than saturated PA, and OA can even prevent PA-induced hepatotoxicity.…”

The Aging Human Liver: The Weal and Woe of Evolutionary Legacy

“…Due to the extensive body of evidence supporting an association of dementia and NAFLD, we would thus propose to investigate how the kinetics of hippuric acid relates to the age-dependent dynamic progression of NAFLD and dementia and its associated characteristic organokine changes. While Stern and colleagues had shown that the concentration of hippurate drops most prominently in aged patients suffering from dementia [108], it has been demonstrated that, conversely, elevated levels of hippuric acid correlate with improved metabolic health and hepatic steatosis [112,113,114,115]. Thus, although the exact relationship between the concentration of hippuric acid and metabolic disease is not clear at this time, the level of hippurate obviously is an indicator of hepatic function and/or can reduce the degree of liver damage [115].…”

“…While Stern and colleagues had shown that the concentration of hippurate drops most prominently in aged patients suffering from dementia [108], it has been demonstrated that, conversely, elevated levels of hippuric acid correlate with improved metabolic health and hepatic steatosis [112,113,114,115]. Thus, although the exact relationship between the concentration of hippuric acid and metabolic disease is not clear at this time, the level of hippurate obviously is an indicator of hepatic function and/or can reduce the degree of liver damage [115]. Perspectively, these correlations could be a starting point to aim for arriving at an improved management of those cases of dementia that develop against a background of chronic age-dependent hepatometabolic disease.…”

Proteomics and Metabolomics in Biomedicine

“…Metabolomics approaches have been largely adopted to investigate the changes in nonalcoholic fatty liver disease associated with therapeutic responses [27], to identify known and novel circulating metabolites and metabolic pathways associated with coronary heart disease [28], to find alterations in acylcarnitine levels in the brain of mice with neonatal hypoxic-ischemic brain injury [29], to explore the causes of low serum 25-hydroxyvitamin D after living donor liver transplantation [30], and to analyze the fecal lipidomic profiles of individuals with metabolic syndrome [31]. Moreover, with an application to cancer research, Buszewska-Forajta et al explored the possibility of using citric acid as a potential biomarker for prostate cancer [32].…”