Preoperative serum brain-derived neurotrophic factor as a predictive biomarker for sepsis after living-donor liver transplantation.
immune dysfunction
liver cirrhosis
nutrition
prognosis
sarcopenia
Journal
Hepatology research : the official journal of the Japan Society of Hepatology
ISSN: 1386-6346
Titre abrégé: Hepatol Res
Pays: Netherlands
ID NLM: 9711801
Informations de publication
Date de publication:
Jan 2023
Jan 2023
Historique:
revised:
17
08
2022
received:
22
05
2022
accepted:
28
08
2022
pubmed:
4
9
2022
medline:
4
9
2022
entrez:
3
9
2022
Statut:
ppublish
Résumé
Although the survival rate after living-donor liver transplantation (LDLT) is improving, sepsis still limits the prognosis. Immune dysfunction and sarcopenia are often observed in LDLT patients, and increase susceptibility to infection. Brain-derived neurotrophic factor (BDNF) is a myokine produced by immune cells and skeletal muscle. We aimed to determine whether serum BDNF could be a feasible biomarker for sepsis of LDLT patients. We measured serum samples from 124 patients who underwent LDLT and 9 healthy volunteers for BDNF. We examined its correlation with incidence rate of sepsis. To clarify the source of BDNF, we examined its expression in lymphocytes, skeletal muscle cells, and hepatocytes. Patients who experienced sepsis showed worse short-term survival. Preoperative serum BDNF was lower in LDLT patients compared with healthy volunteers, and was also lower in Child-Pugh C compared with Child-Pugh A or B. Serum BDNF was inversely correlated with Model for End-Stage Liver Disease and controlling nutritional status (CONUT) scores, but had a weak positive correlation with skeletal muscle mass index (SMI). Multivariate analysis revealed that serum BDNF was independently associated with sepsis. Preoperative serum BDNF was a better predictor of sepsis in LDLT patients than CONUT score or SMI. Serum BDNF was positively correlated with lymphocyte counts, especially T cells. In vitro, T cells and skeletal muscle cells produced BDNF. Preoperative serum BDNF could be a predictive biomarker for sepsis after LDLT, by reflecting the systemic condition including hepatic function, nutritional status, and immune status.
Types de publication
Journal Article
Langues
eng
Pagination
72-83Subventions
Organisme : Japan Agency for Medical Research and Development
ID : 21fk0210094
Organisme : Japan Society for the Promotion of Science
ID : 21K08020
Organisme : National Center for Global Health and Medicine
ID : 20A3001
Informations de copyright
© 2022 The Japan Society of Hepatology.
Références
Yoshizumi T, Ikegami T, Bekki Y, Ninomiya M, Uchiyama H, Iguchi T, et al. Re-evaluation of the predictive score for 6-month graft survival in living donor liver transplantation in the modern era. Liver Transpl. 2014 Mar;20(3):323-32. https://doi.org/10.1002/lt.23804
Imai D, Yoshizumi T, Sakata K, Ikegami T, Itoh S, Harada N, et al. Long-term outcomes and risk factors after adult living donor liver transplantation. Transplantation. 2018 Sep;102(9):e382-e91. https://doi.org/10.1097/tp.0000000000002324
Takeda K, Sawada Y, Kumamoto T, Tanaka K, Endo I. Severe sepsis after living donor liver transplantation: risk factors and outcomes. Transplant Proc. 2016 Jul-Aug;48(6):2124-9. https://doi.org/10.1016/j.transproceed.2016.03.040
Kalafateli M, Mantzoukis K, Choi Yau Y, Mohammad AO, Arora S, Rodrigues S, et al. Malnutrition and sarcopenia predict post-liver transplantation outcomes independently of the model for end-stage liver disease score. J Cachexia Sarcopenia Muscle. 2017 Feb;8(1):113-21. https://doi.org/10.1002/jcsm.12095
Kaido T, Mori A, Ogura Y, Ogawa K, Hata K, Yoshizawa A, et al. Pre- and perioperative factors affecting infection after living donor liver transplantation. Nutrition. 2012 Nov-Dec;28(11-12):1104-8. https://doi.org/10.1016/j.nut.2012.02.007
Toshima T, Shirabe K, Kurihara T, Itoh S, Harimoto N, Ikegami T, et al. Profile of plasma amino acids values as a predictor of sepsis in patients following living donor liver transplantation: special reference to sarcopenia and postoperative early nutrition. Hepatol Res. 2015 Dec;45(12):1170-7. https://doi.org/10.1111/hepr.12484
Masuda T, Shirabe K, Ikegami T, Harimoto N, Yoshizumi T, Soejima Y, et al. Sarcopenia is a prognostic factor in living donor liver transplantation. Liver Transpl. 2014 Apr;20(4):401-7. https://doi.org/10.1002/lt.23811
Shirabe K, Yoshimatsu M, Motomura T, Takeishi K, Toshima T, Muto J, et al. Beneficial effects of supplementation with branched-chain amino acids on postoperative bacteremia in living donor liver transplant recipients. Liver Transpl. 2011 Sep;17(9):1073-80. https://doi.org/10.1002/lt.22324
Carson BP. The potential role of contraction-induced myokines in the regulation of metabolic function for the prevention and treatment of type 2 diabetes. Front Endocrinol (Lausanne). 2017;8:97. https://doi.org/10.3389/fendo.2017.00097
Nelke C, Dziewas R, Minnerup J, Meuth SG, Ruck T. Skeletal muscle as potential central link between sarcopenia and immune senescence. EBioMedicine. 2019 Nov;49:381-8. https://doi.org/10.1016/j.ebiom.2019.10.034
Marosi K, Mattson MP. BDNF mediates adaptive brain and body responses to energetic challenges. Trends Endocrinol Metab. 2014 Feb;25(2):89-98. https://doi.org/10.1016/j.tem.2013.10.006
D'Onofrio M, de Grazia U, Morrone S, Cuomo L, Spinsanti P, Frati L, et al. Expression of neurotrophin receptors in normal and malignant B lymphocytes. Eur Cytokine Netw. 2000;11:283-92.
Gielen A, Khademi M, Muhallab S, Olsson T, Piehl F. Increased brain-derived neurotrophic factor expression in white blood cells of relapsing-remitting multiple sclerosis patients. Scand J Immunol. 2003 May;57(5):493-7. https://doi.org/10.1046/j.1365-3083.2003.01260.x
Matthews VB, Astrom MB, Chan MH, Bruce CR, Krabbe KS, Prelovsek O, et al. Brain-derived neurotrophic factor is produced by skeletal muscle cells in response to contraction and enhances fat oxidation via activation of AMP-activated protein kinase. Diabetologia. 2009 Jul;52(7):1409-18. https://doi.org/10.1007/s00125-009-1364-1
Ignacio de Ulibarri J, Gonzalez-Madrono A, de Villar NG, Gonzalez P, Gonzalez B, Mancha A, et al. CONUT: a tool for controlling nutritional status. First validation in a hospital population. Nutr Hosp. 2005 Jan-Feb;20:38-45.
Takagi K, Domagala P, Polak WG, Buettner S, Ijzermans JNM. Prognostic significance of the controlling nutritional status (CONUT) score in patients undergoing hepatectomy for hepatocellular carcinoma: a systematic review and meta-analysis. BMC Gastroenterol. 2019 Dec 9;19(1):211. https://doi.org/10.1186/s12876-019-1126-6
Harimoto N, Yoshizumi T, Izumi T, Motomura T, Harada N, Itoh S, et al. Clinical outcomes of living liver transplantation according to the presence of sarcopenia as defined by skeletal muscle mass, hand grip, and gait speed. Transplant Proc. 2017 Nov;49(9):2144-52. https://doi.org/10.1016/j.transproceed.2017.09.017
Nishikawa H, Shiraki M, Hiramatsu A, Moriya K, Hino K, Nishiguchi S. Japan Society of Hepatology guidelines for sarcopenia in liver disease (1st edition): recommendation from the working group for creation of sarcopenia assessment criteria. Hepatol Res. 2016 Sep;46(10):951-63. https://doi.org/10.1111/hepr.12774
Yamamoto H, Gurney ME. Human platelets contain brain-derived neurotrophic factor. J Neurosci. 1990 Nov;10(11):3469-78. https://doi.org/10.1523/jneurosci.10-11-03469.1990
Yang ZF, Ho DW, Lau CK, Tam KH, Lam CT, Yu WC, et al. Significance of the serum brain-derived neurotrophic factor and platelets in hepatocellular carcinoma. Oncol Rep. 2006 Dec;16:1237-43. https://doi.org/10.3892/or.16.6.1237
Xu H, Zhou Y, Ko F, Ping J, Zhang J, Zhao C, et al. Female gender and gastrointestinal symptoms, not brain-derived neurotrophic factor, are associated with depression and anxiety in cirrhosis. Hepatol Res. 2017 Mar;47(3):E64-73. https://doi.org/10.1111/hepr.12723
Chevrel G, Hohlfeld R, Sendtner M. The role of neurotrophins in muscle under physiological and pathological conditions. Muscle Nerve. 2006 Apr;33(4):462-76. https://doi.org/10.1002/mus.20444
Nishikawa H, Enomoto H, Ishii A, Iwata Y, Miyamoto Y, Ishii N, et al. Elevated serum myostatin level is associated with worse survival in patients with liver cirrhosis. J Cachexia Sarcopenia Muscle. 2017 Dec;8(6):915-25. https://doi.org/10.1002/jcsm.12212
Yoshio S, Shimagaki T, Hashida R, Kawaguchi T, Tsutsui Y, Sakamoto Y, et al. Myostatin as a fibroblast-activating factor impacts on postoperative outcome in patients with hepatocellular carcinoma. Hepatol Res. 2021 Jul;51(7):803-12. https://doi.org/10.1111/hepr.13667
Kawaguchi T, Yoshio S, Sakamoto Y, Hashida R, Koya S, Hirota K, et al. Impact of decorin on the physical function and prognosis of patients with hepatocellular carcinoma. J Clin Med. 2020 Mar 28;9:936.
Noble EE, Billington CJ, Kotz CM, Wang C. The lighter side of BDNF. Am J Physiol Regul Integr Comp Physiol. 2011 May;300(5):R1053-69. https://doi.org/10.1152/ajpregu.00776.2010