"A randomized, double-blind study of the effects of omega-3 fatty acids (Omegaven) on outcome after major liver resection".
BACKGROUND
The body is dependent on the exogenous supply of omega-3 polyunsaturated fatty acids (n3-PUFA). These essential fatty acids are key players in regulating metabolic signaling but also exert anti-inflammatory and anti-carcinogenic properties. The liver is a major metabolic organ involved in fatty acid metabolism. Under experimental conditions, n3-PUFA exert beneficial effect on hepatic steatosis, regeneration and inflammatory insults such as ischemic injury after surgery. Some of these effects have also been observed in human subjects. However, it is unclear whether perioperative administration of n3-PUFA is sufficient to protect the liver from ischemic injury. Therefore, we designed a randomized controlled trial (RCT) assessing n3-PUFA (pre-) conditioning strategies in patients scheduled for liver surgery.


METHODS
The Omegaven trial is a multi-centric, double-blind, randomized, placebo- controlled trial applying two single doses of Omegaven or placebo on 258 patients undergoing major liver resection. Primary endpoints are morbidity and mortality one month after hospital discharge, defined by the Clavien- Dindo classification of surgical complications (Ann Surg 240(2):205-13, 2004) as well as the Comprehensive Complication Index (CCI) (Ann Surg 258(1):1-7, 2013). Secondary outcome variables include length of Intensive Care Unit (ICU) and hospital stay, postoperative liver function tests, fatty acid and eicosanoid concentration, inflammatory markers in serum and in liver tissue. An interim analysis is scheduled after the first 30 patients per randomization group.


CONCLUSIONS
Long-term administration of n3-PUFA have a beneficial effect on metabolism and hepatic injury. Patients often require surgery without much delay, thus long-term n3-PUFA uptake is not possible. Also, lack of compliance may lead to incomplete n3-PUFA substitution. Hence, perioperative Omegaven™ may provide an easy and controllable way to ensure hepaative application of tic protection.


BACKGROUND
ClinicalTrial.gov: ID: NCT01884948 , registered June 14, 2013; Institution Ethical Board Approval: KEK-ZH-Nr. 2010-0038; Swissmedic Notification: 2012DR3215.
Swiss Hepato-Pancreato-Biliary (HPB) and Transplantation Center, University Hospital Zurich, Zurich, Switzerland. michael.linecker@usz.ch.|Department of Surgery & Transplantation, University Hospital Zurich, Raemistrasse 100, CH-8091, Zurich, Switzerland. michael.linecker@usz.ch.
Michael
M
Linecker
Swiss Hepato-Pancreato-Biliary (HPB) and Transplantation Center, University Hospital Zurich, Zurich, Switzerland. perparim.limani@usz.ch.|Department of Surgery & Transplantation, University Hospital Zurich, Raemistrasse 100, CH-8091, Zurich, Switzerland. perparim.limani@usz.ch.
Perparim
P
Limani
Center of General Surgery and Liver Transplantation, Fundeni Institute Bucharest, Bucharest, Romania. florinbotea@gmail.com.
Florin
F
Botea
Center of General Surgery and Liver Transplantation, Fundeni Institute Bucharest, Bucharest, Romania. irinel.popescu220@gmail.com.
Irinel
I
Popescu
Department of Liver and Pancreatic Surgery, Moscow Clinical Scientific Center, Moscow, Russia. r.alikhanov@mknc.ru.
Ruslan
R
Alikhanov
Department of Liver and Pancreatic Surgery, Moscow Clinical Scientific Center, Moscow, Russia. m.efanov@mknc.ru.
Michail
M
Efanov
Department of Liver and Pancreatic Surgery, Moscow Clinical Scientific Center, Moscow, Russia. drpoul@yandex.ru.
Pavel
P
Kim
Department of Liver and Pancreatic Surgery, Moscow Clinical Scientific Center, Moscow, Russia. i.hatkov@mknc.ru.
Igor
I
Khatkov
Swiss Hepato-Pancreato-Biliary (HPB) and Transplantation Center, University Hospital Zurich, Zurich, Switzerland. draptis@btinternet.com.|Department of Surgery & Transplantation, University Hospital Zurich, Raemistrasse 100, CH-8091, Zurich, Switzerland. draptis@btinternet.com.
Dimitri Aristotele
DA
Raptis
Swiss Hepato-Pancreato-Biliary (HPB) and Transplantation Center, University Hospital Zurich, Zurich, Switzerland. christoph.tschuor@usz.ch.|Department of Surgery & Transplantation, University Hospital Zurich, Raemistrasse 100, CH-8091, Zurich, Switzerland. christoph.tschuor@usz.ch.
Christoph
C
Tschuor
Department of Anesthesiology, University Hospital Zurich, Zurich, Switzerland. beatrice.beck@usz.ch.
Beatrice
B
Beck-Schimmer
Department of Anesthesiology, University Hospital Zurich, Zurich, Switzerland. john.bonvini@usz.ch.
John
J
Bonvini
Swiss Hepato-Pancreato-Biliary (HPB) and Transplantation Center, University Hospital Zurich, Zurich, Switzerland. andrea.wirsching@usz.ch.|Department of Surgery & Transplantation, University Hospital Zurich, Raemistrasse 100, CH-8091, Zurich, Switzerland. andrea.wirsching@usz.ch.
Andrea
A
Wirsching
Swiss Hepato-Pancreato-Biliary (HPB) and Transplantation Center, University Hospital Zurich, Zurich, Switzerland. philipp.kron@usz.ch.|Department of Surgery & Transplantation, University Hospital Zurich, Raemistrasse 100, CH-8091, Zurich, Switzerland. philipp.kron@usz.ch.
Philipp
P
Kron
Swiss Hepato-Pancreato-Biliary (HPB) and Transplantation Center, University Hospital Zurich, Zurich, Switzerland. ksenija.slankamenac@usz.ch.|Department of Surgery & Transplantation, University Hospital Zurich, Raemistrasse 100, CH-8091, Zurich, Switzerland. ksenija.slankamenac@usz.ch.
Ksenija
K
Slankamenac
Swiss Hepato-Pancreato-Biliary (HPB) and Transplantation Center, University Hospital Zurich, Zurich, Switzerland. bostjan.humar@usz.ch.|Department of Surgery & Transplantation, University Hospital Zurich, Raemistrasse 100, CH-8091, Zurich, Switzerland. bostjan.humar@usz.ch.
Bostjan
B
Humar
Swiss Hepato-Pancreato-Biliary (HPB) and Transplantation Center, University Hospital Zurich, Zurich, Switzerland. rolf.graf@usz.ch.|Department of Surgery & Transplantation, University Hospital Zurich, Raemistrasse 100, CH-8091, Zurich, Switzerland. rolf.graf@usz.ch.
Rolf
R
Graf
Swiss Hepato-Pancreato-Biliary (HPB) and Transplantation Center, University Hospital Zurich, Zurich, Switzerland. henrik.petrowsky@usz.ch.|Department of Surgery & Transplantation, University Hospital Zurich, Raemistrasse 100, CH-8091, Zurich, Switzerland. henrik.petrowsky@usz.ch.
Henrik
H
Petrowsky
Swiss Hepato-Pancreato-Biliary (HPB) and Transplantation Center, University Hospital Zurich, Zurich, Switzerland. clavien@access.uzh.ch.|Department of Surgery & Transplantation, University Hospital Zurich, Raemistrasse 100, CH-8091, Zurich, Switzerland. clavien@access.uzh.ch.
Pierre-Alain
PA
Clavien
D000410:Alanine Transaminase / Q000097:blood; D001219:Aspartate Aminotransferases / Q000097:blood; D004311:Double-Blind Method; D015777:Eicosanoids / Q000097:blood; D005227:Fatty Acids / Q000097:blood; D015525:Fatty Acids, Omega-3 / Q000008:administration & dosage* / Q000378:metabolism; D005395:Fish Oils / Q000008:administration & dosage*; D006498:Hepatectomy / Q000009:adverse effects* / Q000401:mortality; D006801:Humans; D007362:Intensive Care Units; D019194:Ischemic Preconditioning / Q000379:methods; D007902:Length of Stay; D008111:Liver Function Tests; D011446:Prospective Studies; D015427:Reperfusion Injury / Q000209:etiology / Q000517:prevention & control*; D012107:Research Design; D014280:Triglycerides
D015777:Eicosanoids; D005227:Fatty Acids; D015525:Fatty Acids, Omega-3; D005395:Fish Oils; D014280:Triglycerides; C568345:fish oil triglycerides; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase