Randomized Clinical Trial
Copyright ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Hepatol. Mar 27, 2019; 11(3): 305-317
Published online Mar 27, 2019. doi: 10.4254/wjh.v11.i3.305
Preoperative immunonutrition in patients undergoing liver resection: A prospective randomized trial
Kylie Russell, Han-Guang Zhang, Lyn K Gillanders, Adam SJR Bartlett, Helena L Fisk, Philip C Calder, Peter J Swan, Lindsay D Plank
Kylie Russell, Lyn K Gillanders, Nutrition Services, Auckland City Hospital, Auckland 1023, New Zealand
Han-Guang Zhang, Adam SJR Bartlett, Peter J Swan, Lindsay D Plank, Department of Surgery, University of Auckland, Auckland 1023, New Zealand
Adam SJR Bartlett, New Zealand Liver Transplant Unit, Auckland City Hospital, Auckland 1023, New Zealand
Helena L Fisk, Philip C Calder, Human Development and Health, Faculty of Medicine, University of Southampton, Southampton SO171BJ, United Kingdom
Philip C Calder, NIHR Southampton Biomedical Research Centre, University Hospital Southampton NHS Foundation Trust and University of Southampton, Southampton SO166YD, United Kingdom
Author contributions: Russell K, Zhang HG, Gillanders LK, Bartlett AJSR and Plank LD designed the study; Russell K, Zhang HG, Fisk HL, and Plank LD acquired the data; Russell K, Zhang H-G and Plank LD analysed and interpreted the data; Gillanders LK, Bartlett AJSR, Calder PC and Swan PJ contributed to interpretation of the results; Russell K and Plank LD wrote the manuscript; Gillanders LK, Bartlett AJSR, Fisk HL, Calder PC and Swan PJ provided critical revisions of the manuscript; all authors read and approved the final version of the manuscript.
Supported by: Australasian Society for Parenteral and Enteral Nutrition Research Grant and A+ Trust Small Project Grant, No. 5576.
Institutional review board statement: The study was reviewed and approved by the New Zealand Health and Disability Ethics Northern A Committee (NTX/12/06/056).
Clinical trial registration statement: This study is registered with the Australian and New Zealand Clinical Trials Registry (ACTRN12612001151820).
Informed consent statement: All study participants provided written informed consent prior to study enrolment.
Conflict-of-interest statement: None of the authors has any conflicts of interest related to this study.
Data sharing statement: No additional data are available.
CONSORT 2010 statement: The authors have read the CONSORT 2010 Statement and the manuscript was prepared according to the CONSORT 2010 Statement.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Lindsay D Plank, DPhil, Associate Professor, Department of Surgery, University of Auckland, 2 Park Road, Auckland 1023, New Zealand. l.plank@auckland.ac.nz
Telephone: +64-9-9236949 Fax: +64-9-3779656
Received: October 25, 2018
Peer-review started: October 26, 2018
First decision: December 19, 2018
Revised: February 22, 2019
Accepted: March 16, 2019
Article in press: March 16, 2019
Published online: March 27, 2019

Preoperative supplementation with immunonutrients, including arginine and n-3 fatty acids, has been shown in a number of systematic reviews to reduce infectious complications in patients who have undergone gastrointestinal surgery. Limited information, however, is available on the benefits of nutritional supplementation enriched with arginine and n-3 fatty acids in patients undergoing liver resection.


To evaluate the effects of preoperative nutritional supplementation enriched with arginine and n-3 fatty acids on inflammatory and immunologic markers and clinical outcome in patients undergoing liver resection.


Thirty-four patients undergoing liver resection were randomized to either five days of preoperative Impact® [1020 kcal/d, immunonutrition (IMN) group], or standard care [no supplementation, standard care (STD) group]. Nutritional status was measured at study entry by subjective global assessment (SGA). Functional assessments (grip strength, fatigue and performance status) were carried out at study entry, on the day prior to surgery, and on postoperative day (POD) 7 and 30. Inflammatory and immune markers were measured at study entry, on the day prior to surgery, and POD 1, 3, 5, 7, 10 and 30. Postoperative complications were recorded prospectively until POD30.


A total of 32 patients (17 IMN and 15 STD) were analysed. All except four patients were SGA class A. The plasma ratio of (eicosapentaenoic acid plus docosahexaenoic acid) to arachidonic acid was higher in IMN patients on the day prior to surgery and POD 1, 3, 5 and 7 (P < 0.05). Plasma interleukin (IL)-6 concentrations were elevated in the IMN group (P = 0.017 for POD7). No treatment effect was detected for functional measures, immune response (white cell count and total lymphocytes) or markers of inflammation (C-reactive protein, tumour necrosis factor-α, IL-8, IL-10). There were 10 patients with infectious complications in the IMN group and 4 in the STD group (P = 0.087). Median hospital stay was 9 (range 4–49) d in the IMN group and 8 (3-34) d in the STD group (P = 0.476).


In well-nourished patients undergoing elective liver resection, this study failed to show any benefit of preoperative immunonutrition.

Keywords: Liver cancer, Partial hepatectomy, Fish oil, Arginine, Nutritional status, Inflammation

Core tip: Whether immunonutritional supplementation provided preoperatively to patients undergoing liver resection can reduce postoperative inflammation and improve clinical outcome compared to standard care remains unclear. We conducted a prospective randomized trial to clarify this. We found no significant suppression of postoperative inflammation or reduction in infectious complications or length of hospital stay post-surgery through providing preoperative immunonutrition.