Effect of obeticholic acid on liver regeneration following portal vein embolization in an experimental model

P. B. Olthof*, F. Huisman, F. G. Schaap, K. P. van Lienden, R. J. Bennink, R. F. van Golen, M. Heger, J. Verheij, P. L. Jansen, S. W. Olde Damink, T. M. van Gulik

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

BackgroundThe bile salt-activated transcription factor farnesoid X receptor (FXR) is a key mediator of proliferative bile salt signalling, which is assumed to play a role in the early phase of compensatory liver growth. The aim of this study was to evaluate the effect of a potent FXR agonist (obeticholic acid, OCA) on liver growth following portal vein embolization (PVE).

MethodsRabbits were allocated to receive daily oral gavage with OCA (10mg/kg) or vehicle (control group) starting 7days before PVE (n=18 per group), and continued until 7days after PVE. PVE of the cranial liver lobes was performed using polyvinyl alcohol particles and coils on day 0. Caudal liver volume (CLV) was analysed by CT volumetry on days -7, -1, +3 and +7. Liver function was determined by measuring mebrofenin uptake using hepatobiliary scintigraphy. Additional parameters analysed were plasma aminotransferase levels, and histological scoring of haematoxylin and eosin- and Ki-67-stained liver sections.

ResultsThree days after PVE of the cranial lobes, the increase in CLV was 22-fold greater in the OCA group than in controls (mean(s.d.) 561(203) versus 261(154) per cent respectively; P

ConclusionOCA accelerated liver regeneration after PVE in a rabbit model. OCA treatment might increase the efficacy of PVE and, thereby, resectability.

Original languageEnglish
Pages (from-to)590-599
Number of pages10
JournalBritish Journal of Surgery
Volume104
Issue number5
DOIs
Publication statusPublished - Apr 2017

Keywords

  • FARNESOID-X RECEPTOR
  • HEPATOCELLULAR-CARCINOMA
  • HEPATIC RESECTION
  • HEPATECTOMY
  • GROWTH
  • MICE
  • FXR
  • PROLIFERATION
  • HYPERTROPHY
  • LIGATION

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