Fatty Acids Lipidome and Oxidative Stress in Liver Transplantation

Fatty Acids Lipidome and Oxidative Stress Markers as Indicators of Liver Transplant Outcome

The purpose of this study is to determine lipid metabolism in chronic liver disease in the attempt to find a useful biomarker of liver function and of prognostic value of graft function in those patients who undergo liver transplant. The present study enrolls subjects with liver cirrhosis (with different ethiology), including subjects eligible for a full-size liver transplantation, and healthy controls.

Liver has a central role in fatty acids metabolism that is impaired in chronic liver diseases. Polyunsaturated fatty acids are reportedly reduced in liver cirrhosis, which is considered a condition of essential fatty acids deficiency. However, there is a paucity of data concerning the level of the multitude of circulating fatty acids in liver cirrhosis. Oxidative stress is involved in the pathogenesis of chronic liver disease and fibrosis. Increased oxidative stress with impaired antioxidant status at the systemic level has been described in different chronic liver diseases and negatively influences graft function after liver transplantation (Poli G. 2000, Loguercio C 2003). 7-Ketocholesterol and 7beta-hydroxycholesterol, prototype molecules of free radical-mediated cholesterol oxidation, are very important oxysterols currently accepted as in vivo reliable markers of oxidative stress. High oxysterols plasma levels are associated with an alteration of normal plasma fatty acid pattern in cystic fibrosis (Iuliano 2009). The Model for End-Stage Liver Disease (MELD) score is a common score used routinely to stage liver function in patients with liver cirrhosis (Al Sibae 2010). After ischemia-reperfusion injury at liver transplantation oxidative stress, hepatic endoplasmic reticulum (ER) stress and cholesterol metabolism are interrelated key processes to preserve graft regeneration and function. A blood sample is obtained in each subject to measure MELD score at the first visit and at liver transplantation. Further blood samples are collected at days seven and 30 post transplantation. Blood samples are also obtained from healthy subjects. Liver biopsy samples are obtained from liver transplant donors. Oxidative stress and fatty acids lipidomics are measured to evaluate the actual plasma concentration in liver cirrhosis patients to be compared with healthy controls. Oxidative stress and fatty acids are also analyzed as a function of disease status, and for its influence on transplant outcomes. Lipid metabolism gene and endoplasmic stress reticulum gene expression are evaluated in liver biopsy specimen to study the influence on graft function.

Liver cirrhosis inclusion criteria:

• subjects with liver cirrhosis eligible for liver transplant, and one MELD score determination performed at least 3 months before liver transplantation

Liver cirrhosis exclusion criteria:

• liver transplant contraindication and re-transplantation
• current use of antioxidants and fatty acids supplements

Healthy controls are recruited recruited among the University personnel, after a review of their medical history.

Exclusion criteria for control participants included the use of drugs that affect fatty acids (systemic corticosteroids, isotretinoin, and ursodiol) and/or oxidative stress (antioxidants and hypolipemic drugs).