title: 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.
authors.affiliation: Baker IDI Heart and Diabetes Institute, Melbourne, Vic 3004, Australia.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Meikle
authors.affiliation: Baker IDI Heart and Diabetes Institute, Melbourne, Vic 3004, Australia.
authors.forename: Piyushkumar A
authors.initials: PA
authors.lastname: Mundra
authors.affiliation: Baker IDI Heart and Diabetes Institute, Melbourne, Vic 3004, Australia.
authors.forename: Gerard
authors.initials: G
authors.lastname: Wong
authors.affiliation: Discipline of Clinical Medicine & Addiction Medicine, Faculty of Medicine, University of Sydney, Sydney, NSW 2006, Australia.
authors.forename: Khairunnessa
authors.initials: K
authors.lastname: Rahman
authors.affiliation: Baker IDI Heart and Diabetes Institute, Melbourne, Vic 3004, Australia.
authors.forename: Kevin
authors.initials: K
authors.lastname: Huynh
authors.affiliation: Baker IDI Heart and Diabetes Institute, Melbourne, Vic 3004, Australia.
authors.forename: Christopher K
authors.initials: CK
authors.lastname: Barlow
authors.affiliation: Garvan Institute of Medical Research, Darlinghurst, NSW 2010, Australia.
authors.forename: Alastair M P
authors.initials: AM
authors.lastname: Duly
authors.affiliation: Discipline of Clinical Medicine & Addiction Medicine, Faculty of Medicine, University of Sydney, Sydney, NSW 2006, Australia; Drug Health Services and Centenary Institute of Cancer Medicine and Cell Biology, Royal Prince Alfred Hospital, Camperdown, NSW 2050, Australia.
authors.forename: Paul S
authors.initials: PS
authors.lastname: Haber
authors.affiliation: Genetic Epidemiology, QIMR Berghofer Medical Research Institute, Herston, Queensland 4029, Australia.
authors.forename: John B
authors.initials: JB
authors.lastname: Whitfield
authors.affiliation: Discipline of Clinical Medicine & Addiction Medicine, Faculty of Medicine, University of Sydney, Sydney, NSW 2006, Australia; Drug Health Services and Centenary Institute of Cancer Medicine and Cell Biology, Royal Prince Alfred Hospital, Camperdown, NSW 2050, Australia.
authors.forename: Devanshi
authors.initials: D
authors.lastname: Seth
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood*; D005260:Female; D006801:Humans; D008055:Lipids / Q000097:blood*; D008104:Liver Cirrhosis, Alcoholic / Q000097:blood*; D008297:Male; D008875:Middle Aged
chemical_list: D015415:Biomarkers; D008055:Lipids