P. B. Olthof1, F. Huisman1, K. Van Lienden2, R. F. Van Golen1, M. Heger1, J. Verheij3, F. F. Schaap4, P. L. Jansen4, S. W. Olde Damink4, T. Van Gulik1 1Academic Medical Center,Surgery,Amsterdam, ZUID-HOLLAND, Netherlands 2Academic Medical Center,Radiology,Amsterdam, ZUID-HOLLAND, Netherlands 3Academic Medical Center,Pathology,Amsterdam, ZUID-HOLLAND, Netherlands 4NUTRIM School Of Nutrition And Translational Research In Metabolism, Maastricht University,Surgery,Maastricht, LIMBURG, Netherlands
Introduction: Portal vein embolization (PVE) is used to increase future remnant liver volume in patients scheduled for major liver surgery. The bile salt-activated transcription factor farnesoid X-receptor (FXR) is a key mediator of bile salt signaling, an event implicated in the early phase of liver regeneration following partial hepatectomy. The aim of this study was to evaluate the effect of a potent FXR agonist (obeticholic acid, OCA) on PVE-induced liver hypertrophy.
Methods: Twenty-four rabbits (female, 2.9±0.4kg) were given a daily oral gavage with OCA (10mg/kg) or vehicle starting 7 days pre-PVE until 7 days post-PVE of the cranial liver lobes. Effectiveness of the embolization procedure (coils, PVA particles) was confirmed by portography. Caudal liver volume (CLV) was analyzed by CT-volumetric analysis at days -7, -1, +3 and +7. Rabbits were sacrificed at day +3 and +7.
Results:Three days after PVE the increase in CLV was 2.0-fold (59.3 ± 19.2% vs. 29.7 ± 16.1, p=0.0013) greater in the OCA group compared to controls. No differences in CLV increase were measured after 7 days. OCA had no effect on volume of the atrophic cranial lobes at the respective time points. Likewise, OCA did not cause spontaneous liver growth, as liver volume before PVE was proportional to body weight increase over the days before PVE.
Conclusion:Obeticholic acid accelerated liver regeneration in a rabbit model of PVE by 2.0-fold over the first 3 days. The ultimate increase in CLV is the same in both groups. OCA treatment has potential in extending resectability as well as the prevention of postoperative liver failure.