Somatostatin as Inflow Modulator in Liver-transplant Recipients With Severe Portal Hypertension: A Randomized Trial

Roberto Ivan Troisi, Aude Vanlander, Mariano Cesare Giglio, Jurgen Van Limmen, Luigia Scudeller, Bjorn Heyse, Luc De Baerdemaeker, Alexander Croo, Dirk Voet, Marleen Praet, Anne Hoorens, Giulia Antoniali, Erika Codarin, Gianluca Tell, Hendrik Reynaert, Isabelle Colle, Mauricio Sainz-Barriga

Research output: Contribution to journalArticle

Abstract

OBJECTIVE: To investigate the safety and efficacy of somatostatin as liver inflow modulator in patients with end-stage liver disease (ESLD) and clinically significant portal hypertension (CSPH) undergoing liver transplantation (LT) (ClinicalTrials.gov number,01290172).

BACKGROUND: In LT, portal hyperperfusion can severely impair graft function and survival, mainly in cases of partial LT.

METHODS: Thirty-three patients undergoing LT for ESLD and CSPH were randomized double-blindly to receive somatostatin or placebo (2:1). The study drug was administered intraoperatively as 5-mL bolus (somatostatin: 500 μg), followed by a 2.5 mL/h infusion (somatostatin: 250 μg/h) for 5 days. Hepatic and systemic hemodynamics were measured, along with liver function tests and clinical outcomes. The ischemia-reperfusion injury (IRI) was analyzed through histological and protein expression analysis.

RESULTS: Twenty-nine patients (18 receiving somatostatin, 11 placebo) were included in the final analysis. Ten patients responded to somatostatin bolus, with a significant decrease in hepatic venous portal gradient (HVPG) and portal flow of -28.3% and -29.1%, respectively. At graft reperfusion, HVPG was lower in patients receiving somatostatin (-81.7% vs -58.8%; P = 0.0084), whereas no difference was observed in the portal flow (P = 0.4185). Somatostatin infusion counteracted the decrease in arterial flow (-10% vs -45%; P = 0.0431). There was no difference between the groups in the severity of IRI, incidence of adverse events, long-term complications, graft, and patient survival.

CONCLUSIONS: Somatostatin infusion during LT in patients with CSPH is safe, reduces the HVPG, and preserves the arterial inflow to the graft. This study establishes the efficacy of somatostatin as a liver inflow modulator.

Original languageEnglish
JournalAnnals of Surgery
DOIs
Publication statusE-pub ahead of print - Sep 21 2018

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Portal Hypertension
Somatostatin
Liver
Liver Transplantation
End Stage Liver Disease
Graft Survival
Reperfusion Injury
Placebos
Transplant Recipients
Transplants
Liver Function Tests
Reperfusion
Hemodynamics
Safety
Incidence

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Somatostatin as Inflow Modulator in Liver-transplant Recipients With Severe Portal Hypertension : A Randomized Trial. / Troisi, Roberto Ivan; Vanlander, Aude; Giglio, Mariano Cesare; Van Limmen, Jurgen; Scudeller, Luigia; Heyse, Bjorn; De Baerdemaeker, Luc; Croo, Alexander; Voet, Dirk; Praet, Marleen; Hoorens, Anne; Antoniali, Giulia; Codarin, Erika; Tell, Gianluca; Reynaert, Hendrik; Colle, Isabelle; Sainz-Barriga, Mauricio.

In: Annals of Surgery, 21.09.2018.

Research output: Contribution to journalArticle

Troisi, RI, Vanlander, A, Giglio, MC, Van Limmen, J, Scudeller, L, Heyse, B, De Baerdemaeker, L, Croo, A, Voet, D, Praet, M, Hoorens, A, Antoniali, G, Codarin, E, Tell, G, Reynaert, H, Colle, I & Sainz-Barriga, M 2018, 'Somatostatin as Inflow Modulator in Liver-transplant Recipients With Severe Portal Hypertension: A Randomized Trial', Annals of Surgery. https://doi.org/10.1097/SLA.0000000000003062
Troisi, Roberto Ivan ; Vanlander, Aude ; Giglio, Mariano Cesare ; Van Limmen, Jurgen ; Scudeller, Luigia ; Heyse, Bjorn ; De Baerdemaeker, Luc ; Croo, Alexander ; Voet, Dirk ; Praet, Marleen ; Hoorens, Anne ; Antoniali, Giulia ; Codarin, Erika ; Tell, Gianluca ; Reynaert, Hendrik ; Colle, Isabelle ; Sainz-Barriga, Mauricio. / Somatostatin as Inflow Modulator in Liver-transplant Recipients With Severe Portal Hypertension : A Randomized Trial. In: Annals of Surgery. 2018.
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title = "Somatostatin as Inflow Modulator in Liver-transplant Recipients With Severe Portal Hypertension: A Randomized Trial",
abstract = "OBJECTIVE: To investigate the safety and efficacy of somatostatin as liver inflow modulator in patients with end-stage liver disease (ESLD) and clinically significant portal hypertension (CSPH) undergoing liver transplantation (LT) (ClinicalTrials.gov number,01290172).BACKGROUND: In LT, portal hyperperfusion can severely impair graft function and survival, mainly in cases of partial LT.METHODS: Thirty-three patients undergoing LT for ESLD and CSPH were randomized double-blindly to receive somatostatin or placebo (2:1). The study drug was administered intraoperatively as 5-mL bolus (somatostatin: 500 μg), followed by a 2.5 mL/h infusion (somatostatin: 250 μg/h) for 5 days. Hepatic and systemic hemodynamics were measured, along with liver function tests and clinical outcomes. The ischemia-reperfusion injury (IRI) was analyzed through histological and protein expression analysis.RESULTS: Twenty-nine patients (18 receiving somatostatin, 11 placebo) were included in the final analysis. Ten patients responded to somatostatin bolus, with a significant decrease in hepatic venous portal gradient (HVPG) and portal flow of -28.3{\%} and -29.1{\%}, respectively. At graft reperfusion, HVPG was lower in patients receiving somatostatin (-81.7{\%} vs -58.8{\%}; P = 0.0084), whereas no difference was observed in the portal flow (P = 0.4185). Somatostatin infusion counteracted the decrease in arterial flow (-10{\%} vs -45{\%}; P = 0.0431). There was no difference between the groups in the severity of IRI, incidence of adverse events, long-term complications, graft, and patient survival.CONCLUSIONS: Somatostatin infusion during LT in patients with CSPH is safe, reduces the HVPG, and preserves the arterial inflow to the graft. This study establishes the efficacy of somatostatin as a liver inflow modulator.",
author = "Troisi, {Roberto Ivan} and Aude Vanlander and Giglio, {Mariano Cesare} and {Van Limmen}, Jurgen and Luigia Scudeller and Bjorn Heyse and {De Baerdemaeker}, Luc and Alexander Croo and Dirk Voet and Marleen Praet and Anne Hoorens and Giulia Antoniali and Erika Codarin and Gianluca Tell and Hendrik Reynaert and Isabelle Colle and Mauricio Sainz-Barriga",
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T1 - Somatostatin as Inflow Modulator in Liver-transplant Recipients With Severe Portal Hypertension

T2 - A Randomized Trial

AU - Troisi, Roberto Ivan

AU - Vanlander, Aude

AU - Giglio, Mariano Cesare

AU - Van Limmen, Jurgen

AU - Scudeller, Luigia

AU - Heyse, Bjorn

AU - De Baerdemaeker, Luc

AU - Croo, Alexander

AU - Voet, Dirk

AU - Praet, Marleen

AU - Hoorens, Anne

AU - Antoniali, Giulia

AU - Codarin, Erika

AU - Tell, Gianluca

AU - Reynaert, Hendrik

AU - Colle, Isabelle

AU - Sainz-Barriga, Mauricio

PY - 2018/9/21

Y1 - 2018/9/21

N2 - OBJECTIVE: To investigate the safety and efficacy of somatostatin as liver inflow modulator in patients with end-stage liver disease (ESLD) and clinically significant portal hypertension (CSPH) undergoing liver transplantation (LT) (ClinicalTrials.gov number,01290172).BACKGROUND: In LT, portal hyperperfusion can severely impair graft function and survival, mainly in cases of partial LT.METHODS: Thirty-three patients undergoing LT for ESLD and CSPH were randomized double-blindly to receive somatostatin or placebo (2:1). The study drug was administered intraoperatively as 5-mL bolus (somatostatin: 500 μg), followed by a 2.5 mL/h infusion (somatostatin: 250 μg/h) for 5 days. Hepatic and systemic hemodynamics were measured, along with liver function tests and clinical outcomes. The ischemia-reperfusion injury (IRI) was analyzed through histological and protein expression analysis.RESULTS: Twenty-nine patients (18 receiving somatostatin, 11 placebo) were included in the final analysis. Ten patients responded to somatostatin bolus, with a significant decrease in hepatic venous portal gradient (HVPG) and portal flow of -28.3% and -29.1%, respectively. At graft reperfusion, HVPG was lower in patients receiving somatostatin (-81.7% vs -58.8%; P = 0.0084), whereas no difference was observed in the portal flow (P = 0.4185). Somatostatin infusion counteracted the decrease in arterial flow (-10% vs -45%; P = 0.0431). There was no difference between the groups in the severity of IRI, incidence of adverse events, long-term complications, graft, and patient survival.CONCLUSIONS: Somatostatin infusion during LT in patients with CSPH is safe, reduces the HVPG, and preserves the arterial inflow to the graft. This study establishes the efficacy of somatostatin as a liver inflow modulator.

AB - OBJECTIVE: To investigate the safety and efficacy of somatostatin as liver inflow modulator in patients with end-stage liver disease (ESLD) and clinically significant portal hypertension (CSPH) undergoing liver transplantation (LT) (ClinicalTrials.gov number,01290172).BACKGROUND: In LT, portal hyperperfusion can severely impair graft function and survival, mainly in cases of partial LT.METHODS: Thirty-three patients undergoing LT for ESLD and CSPH were randomized double-blindly to receive somatostatin or placebo (2:1). The study drug was administered intraoperatively as 5-mL bolus (somatostatin: 500 μg), followed by a 2.5 mL/h infusion (somatostatin: 250 μg/h) for 5 days. Hepatic and systemic hemodynamics were measured, along with liver function tests and clinical outcomes. The ischemia-reperfusion injury (IRI) was analyzed through histological and protein expression analysis.RESULTS: Twenty-nine patients (18 receiving somatostatin, 11 placebo) were included in the final analysis. Ten patients responded to somatostatin bolus, with a significant decrease in hepatic venous portal gradient (HVPG) and portal flow of -28.3% and -29.1%, respectively. At graft reperfusion, HVPG was lower in patients receiving somatostatin (-81.7% vs -58.8%; P = 0.0084), whereas no difference was observed in the portal flow (P = 0.4185). Somatostatin infusion counteracted the decrease in arterial flow (-10% vs -45%; P = 0.0431). There was no difference between the groups in the severity of IRI, incidence of adverse events, long-term complications, graft, and patient survival.CONCLUSIONS: Somatostatin infusion during LT in patients with CSPH is safe, reduces the HVPG, and preserves the arterial inflow to the graft. This study establishes the efficacy of somatostatin as a liver inflow modulator.

U2 - 10.1097/SLA.0000000000003062

DO - 10.1097/SLA.0000000000003062

M3 - Article

C2 - 30256226

JO - Annals of Surgery

JF - Annals of Surgery

SN - 0003-4932

ER -