Circulating Lipids Are Associated with Alcoholic Liver Cirrhosis and Represent Potential Biomarkers for Risk Assessment

Abstract

Liver disease is the greatest cause of death related to alcohol and a major public health problem. While excessive alcohol intake results in hepatosteatosis in most individuals, this can progress in some to more severe forms of liver disease including fibrosis and cirrhosis. An ongoing challenge in the management of alcoholic liver disease is the identification of liver injury early in the disease process such that intervention strategies can prevent serious long term outcomes. Given that excessive alcohol consumption results in dysregulation of lipid metabolism we applied lipid profiling technology to characterise and compare serum lipid profiles from excessive chronic drinkers with no liver disease to those with advanced alcoholic cirrhosis. In a cohort of 59 excessive drinkers (31 with liver cirrhosis and 28 with no evidence of liver disease) we used electrospray ionisation tandem mass spectrometry to measure over 300 individual lipid species in serum, including species of the major phospholipid, sphingolipid, glycerolipid and sterol classes. Six of the 25 lipid classes and subclasses were significantly associated with alcoholic liver cirrhosis; these included dihexosylceramide, trihexosylceramide, alkylphosphatidylcholine, lysoalkylphosphatidylcholine, phosphatidylinositol and free cholesterol. Multivariate classification models created with only clinical characteristics gave an optimal model with an AUC of 0.847 and an accuracy of 79.7%. The addition of lipid measurements to the clinical characteristics resulted in models of improved performance with an AUC of 0.892 and accuracy of 81.8%. The gain in AUC and accuracy of the combined models highlight the potential of serum lipids as markers of liver injury in alcoholic liver disease.

Baicalin Ameliorates Liver Injury Induced by Chronic plus Binge Ethanol Feeding by Modulating Oxidative Stress and Inflammation via CYP2E1 and NRF2 in Mice

“…Liver steatosis is a basic hallmark in alcoholic liver disease, and alcohol-induced metabolic alterations lead to increased fatty acid synthesis and decrease fat metabolism [ 22 ]. Circulating lipids are also associated with ALD and proposed as biomarkers in risk assessment [ 23 ]. We have demonstrated increased fat deposition in chronic plus ethanol-fed mice liver by Nile red staining and triglyceride content.…”

Mitochondrial dysfunction-related lipid changes occur in nonalcoholic fatty liver disease progression

“…this has proven to be very difficult because the correlations between blood and liver lipid species drastically decrease after the transition from NAFL to NASH (5). We previously used lipidomics to compare serum lipid profiles from excessive chronic drinkers without liver disease to those with advanced alcoholic cirrhosis, and showed that circulating lipids associate with alcoholic liver cirrhosis and represent potential biomarkers for risk assessment (6). The aim of the current study was to gain a more comprehensive understanding of the hepatic and plasma lipidomic changes in morbidly obese subjects with NAFL or NASH compared with morbidly obese subjects without NAFLD, and to gain insight into lipid species that are linked to disease progression through the different stages of NAFLD.…”

Leptin as a Key Player in Insulin Resistance of Liver Cirrhosis? A Cross-Sectional Study in Liver Transplant Candidates

“…However, a negative correlation with HbA1c indicates an at least partly preserved effect of adiponectin on glucose homeostasis. Since we found no association with indices of insulin sensitivity and beta-cell function, this effect is most likely attributable to the specific effect of adiponectin on the hepatic glucose production via identified regulatory pathways for glucose and lipid metabolism at transcriptional levels [51,52].…”