A 3-month course of long-acting repeatable octreotide (sandostatin LAR) improves portal hypertension in patients with cirrhosis: a randomized controlled study.
OBJECTIVE
In patients with cirrhosis, acute octreotide administration may transiently decrease the hepatic venous pressure gradient (HVPG). Information on long-term effects of octreotide is limited and controversial. We evaluated portal and systemic hemodynamics following a prolonged administration of long-acting octreotide in patients with cirrhosis.


METHODS
Eighteen cirrhotic patients (alcoholic 12; age 55 yr [44-69]; Pugh's score 7.8; HVPG 17.3 mmHg [12-22]), no steatohepatitis on histology, were randomized to intramuscular octreotide 20 mg (group A) q 4 wk for 3 months or placebo (group B) in a double-blind fashion. At baseline and 3 months, we measured the HVPG, systemic hemodynamics, endothelin-1 (ET-1), and vascular endothelial growth factor (VEGF) in hepatic venous blood.


RESULTS
Patients remained compensated except for one episode of infection in each group. At 3 months, the HVPG decreased in group A but not in group B (16.5 +/- 1.3 to 11.8 +/- 1.5 mmHg, P < 0.01; 18.2 +/- 1 to 17 +/- 1.1 mmHg, P= 0.4). Systemic hemodynamics and liver function remained unchanged. In group A, but not in group B, VEGF decreased (21.2 +/- 4.7 to 13.7 +/- 3.5 pg/mL, P < 0.01; 22.5 +/- 7.8 to 19.2 +/- 5.4 pg/mL, P= 0.4). ET-1 remained stable. Changes in HVPG and VEGF were correlated (r = 0.49, P < 0.05).


CONCLUSIONS
Three months of long-acting octreotide in selected cirrhotic patients with portal hypertension decreases the HVPG independent of systemic hemodynamics and liver function. The decrease in VEGF blood levels suggests an improvement in splanchnic hyperemia.
Spahr
Laurent
L
Transplantation Unit, University Hospital, Geneva, Switzerland.
Giostra
Emiliano
E
Frossard
Jean-Louis
JL
Morard
Isabelle
I
Mentha
Gilles
G
Hadengue
Antoine
A
D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D001706:Biopsy; D003692:Delayed-Action Preparations; D004311:Double-Blind Method; D019332:Endothelin-1 / Q000097:blood; D005260:Female; D005500:Follow-Up Studies; D005765:Gastrointestinal Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D006801:Humans; D006975:Hypertension, Portal / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D007124:Immunoenzyme Techniques; D007273:Injections, Intramuscular; D008103:Liver Cirrhosis / Q000097:blood / Q000150:complications* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D015282:Octreotide / Q000008:administration & dosage* / Q000493:pharmacokinetics; D017082:Portal Pressure / Q000502:physiology; D011863:Radioimmunoassay; D012189:Retrospective Studies; D013997:Time Factors; D016896:Treatment Outcome; D014579:Urotensins / Q000097:blood; D042461:Vascular Endothelial Growth Factor A / Q000097:blood
D015415:Biomarkers; D003692:Delayed-Action Preparations; D019332:Endothelin-1; D005765:Gastrointestinal Agents; D014579:Urotensins; D042461:Vascular Endothelial Growth Factor A; C029677:urotensin II; D015282:Octreotide