World Journal of Surgery

, Volume 42, Issue 11, pp 3715–3725 | Cite as

Impact of Enteral Nutrition with an Immunomodulating Diet Enriched with Hydrolyzed Whey Peptide on Infection After Liver Transplantation

  • Naoko Kamo
  • Toshimi KaidoEmail author
  • Yuhei Hamaguchi
  • Ryuji Uozumi
  • Shinya Okumura
  • Atsushi Kobayashi
  • Hisaya Shirai
  • Shintaro Yagi
  • Hideaki Okajima
  • Shinji Uemoto
Original Scientific Report



Infection is a leading cause of death after liver transplantation (LT). Therefore, prevention of infection is crucial for improving outcomes after LT. We examined the impact of early enteral nutrition with an immunomodulating diet (IMD) enriched with hydrolyzed whey peptide (HWP) formulation on infection after living donor LT (LDLT), focusing on sarcopenia.


This study enrolled 279 consecutive patients who underwent primary LDLT at our institute between January 2008 and April 2015. Early enteral nutrition with the IMD enriched with HWP formulation and a conventional elemental diet were started within the first 24 h after surgery for 164 (IMD-HWP) and 115 (conventional) patients. Sequential changes in nutritional parameters, and the incidences of acute cellular rejection (ACR) and bacteremia were compared between the IMD-HWP and control groups. The comparison was made between those members of each group that did or did not exhibit sarcopenia. Risk factors for post-transplant bacteremia were also assessed.


Postoperative nutritional parameters and the incidence of ACR were comparable between the groups, except for the prealbumin level. The incidence of bacteremia was significantly lower in the IMD-HWP group, and among patients without sarcopenia in the IMD-HWP group compared with the conventional group (24.4 vs. 41.7%; P = 0.002 and 20.8 vs. 39.0%; P = 0.040, respectively). Independent risk factor for bacteremia comprised bleeding ≥10,000 mL (P = 0.025). In contrast, enteral nutrition without HWP formulation was not significantly associated with bacteremia. However, enteral nutrition without HWP formulation (P = 0.080), MELD scores (P = 0.097), and ABO incompatibility (P = 0.088) showed a trend toward increased incidence of bacteremia, although they did not reach statistical significance in the multivariate analysis.


Postoperative immunonutrition with an IMD enriched with HWP formulation was closely involved with post-transplant bacteremia.



Acute cellular rejection


Branched-chain amino acids


Cold ischemic time


Computed tomography


Living donor


Liver transplantation


Graft/recipient body weight ratio


Model for end-stage liver disease


Immunomodulating diet


Hydrolyzed whey peptide


Odds ratio


Skeletal muscle mass index


Total lymphocyte count


Warm ischemic time



The authors would like to thank Ms. Mayumi Kawashima for her help with collecting the data for this study and Dr. Amr Badawy for English editing.

Compliance with ethical standards

Conflict of interest

None of the authors have any conflicts of interest and any grants to declare.


  1. 1.
    Selberg O, Böttcher J, Tusch G et al (1997) Identification of high and low-risk patients before liver transplantation: a prospective cohort study of nutritional and metabolic parameters in 150 patients. Hepatology 25:652–657CrossRefGoogle Scholar
  2. 2.
    Sanchez AJ, Aranda-Michel J (2006) Nutrition for the liver transplant patient. Liver Transpl 12:1310–1316CrossRefGoogle Scholar
  3. 3.
    Stickel F, Inderbitzin D, Candinas D (2008) Role of nutrition in liver transplantation for end-stage chronic liver disease. Nutr Rev 66:47–54CrossRefGoogle Scholar
  4. 4.
    Kaido T, Egawa H, Tsuji H et al (2009) In-hospital mortality in adult recipients of living donor liver transplantation: experience of 576 consecutive cases at a single center. Liver Transpl 15:1420–1425CrossRefGoogle Scholar
  5. 5.
    Weimann A, Braga M, Harsanyi L et al (2006) ESPEN guidelines on enteral nutrition: surgery including organ transplantation. Clin Nutr 2:224–244CrossRefGoogle Scholar
  6. 6.
    Cerantola Y, Hübner M, Grass F et al (2011) Immunonutrition in gastrointestinal surgery. Br J Surg 98:37–48CrossRefGoogle Scholar
  7. 7.
    Marik PE, Zaloga GP (2010) Immunonutrition in high-risk surgical patients: a systematic review and analysis of the literature. JPEN J Parenter Enter Nutr 34:378–386CrossRefGoogle Scholar
  8. 8.
    Osland E, Hossain MB, Khan S et al (2014) Effect of timing of pharmaconutrition (immunonutrition) administration on outcomes of elective surgery for gastrointestinal malignancies: a systematic review and meta-analysis. JPEN J Parenter Enter Nutr 38:53–69CrossRefGoogle Scholar
  9. 9.
    Mazaki T, Ishii Y, Murai I (2015) Immunoenhancing enteral and parenteral nutrition for gastrointestinal surgery: a multiple-treatments meta-analysis. Ann Surg 261:662–669CrossRefGoogle Scholar
  10. 10.
    Song GM, Tian X, Zhang L et al (2015) Immunonutrition support for patients undergoing surgery for gastrointestinal malignancy: preoperative, postoperative, or perioperative? A Bayesian network meta-analysis of randomized controlled trials. Med Baltim 94:e1225CrossRefGoogle Scholar
  11. 11.
    Marshall K (2004) Therapeutic applications of whey protein. Altem Med Rev 9:136–156Google Scholar
  12. 12.
    Kaido T, Mori A, Ogura Y et al (2010) Impact of enteral nutrition using a new immuno-modulating diet after liver transplantation. Hepatogastroenterology 57:1522–1525PubMedGoogle Scholar
  13. 13.
    Kaido T, Ogura Y, Ogawa K et al (2012) Effect of post-transplant enteral nutrition with an immunomodulating diet containing hydrolyzed whey peptide after liver transplantation. World J Surg 36:1666–1671. CrossRefPubMedGoogle Scholar
  14. 14.
    Lei Q, Wang X, Zheng H et al (2015) Peri-operative immunonutrition in patients undergoing liver transplantation: a meta-analysis of randomized controlled trials. Asia Pac J Clin Nutr 24:583–590PubMedGoogle Scholar
  15. 15.
    Plank LD, Mathur S, Gane EJ et al (2015) Perioperative immunonutrition in patients undergoing liver transplantation: a randomized double-blind trial. Hepatology 61:639–647CrossRefGoogle Scholar
  16. 16.
    Peng PD, van Vledder MG, Tsai S et al (2011) Sarcopenia negatively impacts short-term outcomes in patients undergoing hepatic resection for colorectal liver metastasis. HBP Oxf 13:439–446CrossRefGoogle Scholar
  17. 17.
    van Vledder MG, Levolger S, Ayez N et al (2012) Body composition and outcome in patients undergoing resection of colorectal liver metastases. Br J Surg 99:550–557CrossRefGoogle Scholar
  18. 18.
    Kaido T, Mori A, Ogura Y et al (2012) Pre- and perioperative factors affecting infection after living donor liver transplantation. Nutrition 28:1104–1108CrossRefGoogle Scholar
  19. 19.
    Kaido T, Ogawa K, Fujimoto Y et al (2013) Impact of sarcopenia on survival in patients undergoing living donor liver transplantation. Am J Transpl 13:1549–1556CrossRefGoogle Scholar
  20. 20.
    Ito T, Kiuchi T, Egawa H et al (2003) Surgery-related morbidity in living donors of right-lobe liver graft: lessons from the first 200 cases. Transplantation 76:158–163CrossRefGoogle Scholar
  21. 21.
    Morioka D, Egawa H, Kasahara M et al (2007) Outcomes of adult-to-adult living donor liver transplantation: a single institution’s experience with 335 consecutive cases. Ann Surg 245:315–325CrossRefGoogle Scholar
  22. 22.
    Fukumitsu K, Hammad A, Kaido T et al (2015) Validation of steroid-free immunosuppression regimen after liver transplantation. J Clin Gastroenterol Treat 1:1–4CrossRefGoogle Scholar
  23. 23.
    Hamaguchi U, Kaido Toshimi, Okumura S et al (2017) Impact of skeletal muscle mass index, intramuscular adipose tissue content, and visceral to subcutaneous adipose tissue area ratio on early mortality of living donor liver transplantation. Transplantation 101:565–574CrossRefGoogle Scholar
  24. 24.
    Calder P (2007) Immunonutrition in surgical and critically ill patients. Br J Nutr 98(Suppl 1):S133–S139PubMedGoogle Scholar
  25. 25.
    Kume H, Okazaki K, Yamaji T et al (2012) A newly designed enteral formula containing whey peptides and fermented milk product protects mice against concanavalin A-induced hepatitis by suppressing overproduction of inflammatory cytokines. Clin Nutr 31:283–289CrossRefGoogle Scholar
  26. 26.
    Jobara K, Kaido T, Hori T et al (2014) Whey-hydrolyzed peptide-enriched immunomodulating diet prevents progression of liver cirrhosis in rats. Nutrition 30:1195–1207CrossRefGoogle Scholar

Copyright information

© Société Internationale de Chirurgie 2018

Authors and Affiliations

  • Naoko Kamo
    • 1
  • Toshimi Kaido
    • 1
    Email author
  • Yuhei Hamaguchi
    • 1
  • Ryuji Uozumi
    • 2
  • Shinya Okumura
    • 1
  • Atsushi Kobayashi
    • 1
  • Hisaya Shirai
    • 1
  • Shintaro Yagi
    • 1
  • Hideaki Okajima
    • 1
  • Shinji Uemoto
    • 1
  1. 1.Division of Hepato-Biliary-Pancreatic and Transplant Surgery, Department of Surgery, Graduate School of MedicineKyoto UniversityKyotoJapan
  2. 2.Department of Biomedical Statistics and BioinformaticsKyoto University Graduate School of MedicineKyotoJapan

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