Circulating lipids are associated with alcoholic liver cirrhosis and represent potential biomarkers for risk assessment

Peter J. Meikle, Piyushkumar A Mundra, Gerard Wong, Khairunnessa Rahman, Kevin Huynh, Christopher K. Barlow, Alastair M.P. Duly, Paul S. Haber, John B. Whitfield, Devanshi Seth

Research output: Contribution to journalArticleResearchpeer-review

13 Citations (Scopus)

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 fromexcessive 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 tomeasure 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 inmodels 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.

Original languageEnglish
Article numbere0130346
Number of pages13
JournalPLoS ONE
Volume10
Issue number6
DOIs
Publication statusPublished - 24 Jun 2015
Externally publishedYes

Keywords

  • lipids
  • cirrhosis
  • alcohol consumption
  • liver diseases
  • fatty liver
  • alcoholics
  • cholesterol
  • alcoholic liver disease

Cite this

Meikle, Peter J. ; Mundra, Piyushkumar A ; Wong, Gerard ; Rahman, Khairunnessa ; Huynh, Kevin ; Barlow, Christopher K. ; Duly, Alastair M.P. ; Haber, Paul S. ; Whitfield, John B. ; Seth, Devanshi. / Circulating lipids are associated with alcoholic liver cirrhosis and represent potential biomarkers for risk assessment. In: PLoS ONE. 2015 ; Vol. 10, No. 6.
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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 fromexcessive 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 tomeasure 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 inmodels 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.",
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Circulating lipids are associated with alcoholic liver cirrhosis and represent potential biomarkers for risk assessment. / Meikle, Peter J.; Mundra, Piyushkumar A; Wong, Gerard; Rahman, Khairunnessa; Huynh, Kevin; Barlow, Christopher K.; Duly, Alastair M.P.; Haber, Paul S.; Whitfield, John B.; Seth, Devanshi.

In: PLoS ONE, Vol. 10, No. 6, e0130346, 24.06.2015.

Research output: Contribution to journalArticleResearchpeer-review

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AU - Mundra, Piyushkumar A

AU - Wong, Gerard

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AU - Barlow, Christopher K.

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AB - 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 fromexcessive 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 tomeasure 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 inmodels 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.

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