Evaluation of Efficacy and Safety of Somatostatin Used as Inflow Modulator in Liver Transplantation.

• To elucidate pathophysiological pathways in non-cirrhotic grafted livers. [ Time Frame: 35 days ] [ Designated as safety issue: No ]
• To evaluate the reduction of ischemia-reperfusion injury (cytoprotective effect) [ Time Frame: 1 hour after reperfusion and 5 days ] [ Designated as safety issue: No ]
• To evaluate the efficacy of Somatostatin in the prevention of the small-for-size syndrome (SFSS) in partial liver transplantation. [ Time Frame: after 35 days ] [ Designated as safety issue: No ]

• To elucidate pathophysiological pathways in non-cirrhotic grafted livers. [ Time Frame: 35 days ] [ Designated as safety issue: No ]
• To evaluate the reduction of ischemia-reperfusion injury (cytoprotective effect) [ Time Frame: after 5 days ] [ Designated as safety issue: No ]
• To evaluate the efficacy of Somatostatin in the prevention of the small-for-size syndrome (SFSS) in partial liver transplantation. [ Time Frame: after 35 days ] [ Designated as safety issue: No ]

This study is a 5 day, single-center, randomized, double blind, placebo-controlled study to evaluate the efficacy and safety of Somatostatin used as inflow modulator in liver transplantation. Patient systemic and hepatic dynamics will be collected and recorded at predefined time-points. To evaluate the ischemia-reperfusion injury, it is planned to perform liver biopsies at two different time-points to compare the liver structure and proteomic variations.

• Drug: Administration of Somatostatin

  6 mg will be diluted in saline in a 60 cc syringe to be infused over 24 h (250 mcg/h). The treatment will be started during the hepatectomy phase, after 1st measurement of native arterial and portal flow and pressure and given a clinically significant portal hypertension (CSPH) with a hepatic venous pressure gradient (HVPG) >= 10 mmHg.

  5 cc will be injected in 2 minutes as a single bolus of 500 mcg. Somatostatin will be given a second time at the beginning of the warm ischemia time as a continuous infusion of 250 mcg/h(infusion rate 2,5 cc/h). This will allow the time needed for reaching a stable plasma concentration at reperfusion and minimizing risks of secondary effects. After portal revascularization of the liver graft, a new measurement of portal flow and pressure will be performed. Provided a portal vein flow (PVF) >= 90 ml/min * 100 g LW, the remaining 55 cc will be infused for the following 22 h. 6 mg per day of continuous infusion will be continued for 5 days.

• Drug: Administration of placebo

  The placebo treatment will be started during the hepatectomy phase, after the 1st measurement of native arterial and portal flow and pressure and given a clinically significant portal hypertension (CSPH) with a hepatic venous pressure gradient (HVPG) >= 10 mmHg.

  5 cc of the 60 cc solution will be injected in 2 minutes as a single bolus of 500 mcg. The placebo will be given a 2nd time at the beginning of the warm ischemia time as a continuous infusion of 250 mcg/h (infusion rate 2,5 cc/h). This will allow the time needed for reaching a stable plasma concentration at reperfusion and minimizing risks of secondary effects. After portal revascularization of the liver graft, a new measurement of portal flow and pressure will be performed. Provided a portal vein flow (PVF) >= 90 ml/min * 100 gram LW, the remaining 55 cc will be infused for the following 22 h. 6 mg per day of continuous infusion will be continued everyday to complete 5 days of therapy.

• Experimental: Somatostatin
  Patients in this group receive treatment with Somatostatin for 5 days.
  Intervention: Drug: Administration of Somatostatin
• Placebo Comparator: Placebo
  Patients in this group receive a placebo for 5 days.
  Intervention: Drug: Administration of placebo

Inclusion Criteria:

• Ability and willingness to provide written informed consent
• Cirrhotic patients with established clinically significant portal hypertension (CSPH) defined as an increase in hepatic venous pressure gradient >= 10 mmHg
• Recipients who are 18-70 years of age receiving a primary liver transplant from a brain dead donor or living donor
• Whole liver grafts and partial liver grafts can be included

Exclusion Criteria:

• Patients who are recipients of multiple solid organ transplants, or have previously received an organ or tissue transplant that may not be completely resolved by thrombectomy
• HIV positive patients
• Patients with known history of portal thrombosis or diagnosed at the time of transplantation that may not be completely resolved by thrombectomy.
• Patients included in the preoperative assessment without a CSPH at the time of the first intraoperative measurement of portal pressure
• Patients with low portal perfusion (=< 90 ml/min*100 g of LV) measured at the time of operation. Portal flows above this limit can be excluded in the eventuality that, after infusion, the portal perfusion falls below this limit
• Patients with porto-pulmonary hypertension
• Patients with known cardiac arrhythmias
• Recipients of cardiac-dead donors
• Fulminant hepatic failure patients