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

doi:10.1002/bjs.10466

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 journal › Article › Academic › peer-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 language	English
Pages (from-to)	590-599
Number of pages	10
Journal	British Journal of Surgery
Volume	104
Issue number	5
DOIs	https://doi.org/10.1002/bjs.10466
Publication status	Published - Apr 2017

Keywords

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

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10.1002/bjs.10466

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@article{f4071a66420349ddaa1f2e25febacf8f,

title = "Effect of obeticholic acid on liver regeneration following portal vein embolization in an experimental model",

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

keywords = "FARNESOID-X RECEPTOR, HEPATOCELLULAR-CARCINOMA, HEPATIC RESECTION, HEPATECTOMY, GROWTH, MICE, FXR, PROLIFERATION, HYPERTROPHY, LIGATION",

author = "Olthof, {P. B.} and F. Huisman and Schaap, {F. G.} and {van Lienden}, {K. P.} and Bennink, {R. J.} and {van Golen}, {R. F.} and M. Heger and J. Verheij and Jansen, {P. L.} and Damink, {S. W. Olde} and {van Gulik}, {T. M.}",

year = "2017",

month = apr,

doi = "10.1002/bjs.10466",

language = "English",

volume = "104",

pages = "590--599",

journal = "British Journal of Surgery",

issn = "0007-1323",

publisher = "Wiley",

number = "5",

}

TY - JOUR

T1 - Effect of obeticholic acid on liver regeneration following portal vein embolization in an experimental model

AU - Olthof, P. B.

AU - Huisman, F.

AU - Schaap, F. G.

AU - van Lienden, K. P.

AU - Bennink, R. J.

AU - van Golen, R. F.

AU - Heger, M.

AU - Verheij, J.

AU - Jansen, P. L.

AU - Damink, S. W. Olde

AU - van Gulik, T. M.

PY - 2017/4

Y1 - 2017/4

N2 - 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; PConclusionOCA accelerated liver regeneration after PVE in a rabbit model. OCA treatment might increase the efficacy of PVE and, thereby, resectability.

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

KW - FARNESOID-X RECEPTOR

KW - HEPATOCELLULAR-CARCINOMA

KW - HEPATIC RESECTION

KW - HEPATECTOMY

KW - GROWTH

KW - MICE

KW - FXR

KW - PROLIFERATION

KW - HYPERTROPHY

KW - LIGATION

U2 - 10.1002/bjs.10466

DO - 10.1002/bjs.10466

M3 - Article

SN - 0007-1323

VL - 104

SP - 590

EP - 599

JO - British Journal of Surgery

JF - British Journal of Surgery

IS - 5

ER -