Association of lysophosphatidic acid molecules with liver fibrosis – different roles indicated

Abstract Aim: Lysophosphatidic acid (LPA), which is produced by autotaxin (ATX) known as a marker of liver fibrosis, is a member of the group of lysophospholipids that function as extracellular mediators to activate specific G‐protein‐coupled receptors. This lipid is composed of LPA molecules with varied chemical forms that may have different biological roles. The present cross-sectional study was conducted to investigate the associations of various LPA molecules with liver fibrosis. Methods: Forty-six patients affected by various types of liver disease, including 16 with non-alcoholic fatty liver disease, who underwent an ultrasound-guided liver biopsy were recruited for this study. Liver fibrosis was evaluated using histological grading, as well as shear wave velocity (Vs) and serum level of type Ⅳcollagen 7S (T4c7s). Serum levels of LPA molecules were determined using liquid-chromatography tandem mass-spectrometry (LC-MSMS), while ATX in serum was measured by use of an immunoassay. Results: Total LPA showed a significant positive association with fibrosis severity evaluated based on histological grading, Vs, and T4c7s used as parameters, following adjustment for other confounding factors, including disease type, age, gender, body mass index, and high-sensitivity C-reactive protein. This association was replicated when 16:0-LPA was substituted for total LPA. In contrast, when 20:4-LPA was substituted for total LPA, no significant association with liver fibrosis was observed. Additionally, 20:4-LPA did not demonstrate a significant correlation with serum ATX, in contrast to 16:0-LPA as well as total LPA. Conclusions: Although total LPA concentration was shown to be associated with liver fibrosis, the degree of association varied among the different LPA molecule chemical forms, suggesting different pathophysiological roles of individual LPA molecules. The present findings indicate the importance of analyzing individual LPA molecules for determination of association with liver fibrosis and the usefulness of LC-MSMS for that purpose.