Plasma eicosanoids as noninvasive biomarkers of liver fibrosis in patients with nonalcoholic steatohepatitis

Cyrielle Caussy; Jen-Chieh Chuang; Andrew Billin; Tao Hu; Ya Wang; G Mani Subramanian; C Stephen Djedjos; Robert P Myers; Edward A Dennis; Rohit Loomba

doi:10.1177/1756284820923904

Plasma eicosanoids as noninvasive biomarkers of liver fibrosis in patients with nonalcoholic steatohepatitis

Therap Adv Gastroenterol. 2020 May 26:13:1756284820923904. doi: 10.1177/1756284820923904. eCollection 2020.

Authors

Affiliations

¹ Univ Lyon, CarMen Laboratory, INSERM, INRA, INSA Lyon, Université Claude Bernard Lyon 1, Pierre-Bénite, France.
² Gilead Sciences, Inc., Foster City, CA, USA.
³ Department of Pharmacology and Department of Chemistry and Biochemistry, University of California San Diego, 9500 Gilman Drive, MC 0601, La Jolla, CA 92093-0601, USA.
⁴ Division of Gastroenterology, Department of Medicine and Division of Epidemiology, Department of Family and Preventive Medicine, NAFLD Research Center, Division of Gastroenterology and Epidemiology, University of California San Diego, 9500 Gilman Drive, MC 0887, La Jolla, CA 92093-0887 USA.

Abstract

Background: Eicosanoid and related docosanoid polyunsaturated fatty acids (PUFAs) and their oxygenated derivatives have been proposed as noninvasive lipidomic biomarkers of nonalcoholic steatohepatitis (NASH). Therefore, we investigated associations between plasma eicosanoids and liver fibrosis to evaluate their utility in diagnosing and monitoring NASH-related fibrosis.

Methods: Our analysis used baseline eicosanoid data from 427 patients with biopsy-confirmed nonalcoholic fatty liver disease (NAFLD), and longitudinal measurements along with liver fibrosis staging from 63 patients with NASH and stage 2/3 fibrosis followed for 24 weeks in a phase II trial.

Results: At baseline, four eicosanoids were significantly associated with liver fibrosis stage: 11,12-DIHETE, tetranor 12-HETE, adrenic acid, and 14, 15-DIHETE. Over 24 weeks of follow up, a combination of changes in seven eicosanoids [5-HETE, 7,17-DHDPA, adrenic acid, arachidonic acid (AA), eicosapentaenoic acid (EPA), 16-HDOHE, and 9-HODE) had good diagnostic accuracy for the prediction of ⩾1 stage improvement in fibrosis (AUROC: 0.74; 95% CI: 0.62-0.87), and a combination of four eicosanoids (7,17-DHDPA, 14,15-DIHETRE, 9-HOTRE, and free adrenic acid) accurately predicted improvement in hepatic collagen content (AUROC: 0.72; 95% CI: 0.50-0.77).

Conclusion: This study provides preliminary evidence that plasma eicosanoids may serve as noninvasive biomarkers of liver fibrosis and may predict liver fibrosis improvement in NASH.

Keywords: HETE; HETRE; NAFLD; NASH; adrenic acid; arachidonic acid; eicosanoids; fibrosis; lipidomics; liver.