Date Published: January 31, 2019
Publisher: Public Library of Science
Author(s): Katharina Maria Schwarzkopf, Alexander Queck, Dominique Thomas, Carlo Angioni, Chengcong Cai, Ylva Freygang, Sabrina Rüschenbaum, Gerd Geisslinger, Stefan Zeuzem, Christoph Welsch, Christian Markus Lange, Juan J. Loor.
Liver cirrhosis is associated with profound immunodysfunction, i.e. a parallel presence of chronic systemic inflammation and immunosuppression, which can result in acute-on-chronic liver failure (ACLF). Omega-3 fatty acids are precursors of pro-resolving mediators and support the resolution of inflammation.
The aim of this study was to determine plasma levels of omega-3 fatty acids in patients with liver cirrhosis and ACLF.
Patients with liver cirrhosis with and without ACLF were enrolled in a prospective cohort study and analyzed post-hoc for the present sub-study. Clinical data and biomaterials were collected at baseline and at day 7, 28 and after 3 months of follow-up. Plasma concentrations of arachidonic acid (ARA) and docosahexaenoic acid (DHA), which represent key omega-6 and -3 fatty acids, respectively, were quantified and associated with markers of systemic inflammation and severity of liver cirrhosis.
A total of 117 patients were included in the present analyses. Of those, 26 (22.2%), 51 (43.6%) and 40 (34.2%) patients had compensated or decompensated liver cirrhosis, and ACLF. Plasma levels of ARA and DHA were similar in patients with compensated cirrhosis, decompensated cirrhosis, and ACLF. Furthermore, no significant association between plasma ARA or DHA and C-reactive protein or peripheral blood leukocytes were observed (P>0.05).
In our study plasma levels of key omega-3 and omega-6 fatty acid are neither associated with the severity of liver cirrhosis nor with liver-cirrhosis-associated systemic inflammation.
Polyunsaturated fatty acids (PUFA) are important for the structure and function of cell membranes and have additional important functions in regulating immune and inflammatory responses as precursors of eicosanoids, resolvins and other lipid mediators. Eicosanoids (for example prostaglandins and leukotrienes) which are derived from arachidonic acid (ARA) and associated omega-6 PUFAs exhibit pro-inflammatory and pro-coagulatory functions. In contrast, eicosanoids, resolvins and other mediators derived from omega-3 fatty acids such as docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) support the resolution of inflammation [1,2]. Hence, the balance between proinflammatory and proresolving eicosanoids appears to be of pivotal importance for the regulation and appropriate termination of inflammatory response [2,3]. The ratio of omega-6/omega-3 PUFAs is an important health determinant and a shift in the balance towards omega-3 PUFAs leads to a lower death rate in cardiovascular disease [4–6]. A role for omega-3 PUFAs in ameliorating rheumatoid arthritis, asthma as well as diabetes and cancer has also been described [8–10]. In liver disease, omega-3 PUFAs may reduce hepatic lipogenesis, inflammation and hepatic fibrosis[11–13]. A recent meta-analysis conducted by Yan et al. suggests that omega-3 PUFA supplementation may decrease liver fat and hepatic enzyme parameters in patients with non-alcoholic fatty liver disease.
In the present post-hoc-analysis of a prospective cohort study of patients with compensated liver cirrhosis, decompensated liver cirrhosis, or ACLF, plasma levels of ARA and DHA and their ratio are neither associated with the severity of liver disease/survival, nor with the magnitude of liver cirrhosis-associated systemic inflammation. This finding is in contrast to the well-known increase of eicosanoids, i.e. the downstream metabolites of ARA/DHA, in patients with progressive liver disease.