title: MELD and Child-Pugh Scores Are Related to Immune Status of Intrahepatic Natural Killer Cells in Liver Transplant Candidates.
abstract: BACKGROUND
  The role and phenotypic alterations of intrahepatic natural killer (NK) cells in liver disease were investigated. Although intrahepatic NK cells reportedly functionally deteriorate in the fibrotic liver, it remains unclear how the clinical severity of liver disease affects intrahepatic NK cells in patients with advanced liver failure.
  
  
  METHODS
  We analyzed the phenotypic properties of intrahepatic NK cells by using mononuclear cells extracted from ex vivo liver perfusate effluents from patients who underwent liver transplantation. The relationship between the clinical severity of liver disease and the phenotype of intrahepatic NK cells in these patients was also evaluated. To estimate the immunological responsiveness of intrahepatic NK cells, phenotypic enhancement after interleukin-2 stimulation was analyzed.
  
  
  RESULTS
  Intrahepatic NK cells from patients with advanced liver failure exhibited down-regulated monomodal expression of NKp46, a major activating molecule. Notably, the expression level of NKp46 decreased depending on the severity of liver disease, Model for End-Stage Liver Disease score, and Child-Pugh score rather than the etiology. After in vitro recombinant interleukin-2 stimulation, the enhancement of expression of cytotoxic molecules, NKp44, and tumor necrosis factor-related apoptosis-inducing ligand was significantly impaired in intrahepatic NK cells from patients with liver failure, concurrently with decreased expression of CD122 and interleukin-2 receptor beta.
  
  
  CONCLUSIONS
  Our results suggest that terminal deterioration of liver environments by chronic liver disease impairs the potential of local NK cells, depending on the severity of the deterioration. These influences of advanced liver failure on intrahepatic NK cells may be attributed to multicentric carcinogenesis in patients with liver failure.
authors.affiliation: Gastroenterological and Transplant Surgery, Institute of Biomedical & Health Sciences, Hiroshima University, Hiroshima, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Tanimine
authors.affiliation: Gastroenterological and Transplant Surgery, Institute of Biomedical & Health Sciences, Hiroshima University, Hiroshima, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Tanaka
authors.affiliation: Department of Surgery, Onomichi General Hospital, Hiroshima, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Abe
authors.affiliation: Gastroenterological and Transplant Surgery, Institute of Biomedical & Health Sciences, Hiroshima University, Hiroshima, Japan.
authors.forename: J
authors.initials: J
authors.lastname: Piao
authors.affiliation: Gastroenterological and Transplant Surgery, Institute of Biomedical & Health Sciences, Hiroshima University, Hiroshima, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Ishiyama
authors.affiliation: Gastroenterological and Transplant Surgery, Institute of Biomedical & Health Sciences, Hiroshima University, Hiroshima, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Kobayashi
authors.affiliation: Gastroenterological and Transplant Surgery, Institute of Biomedical & Health Sciences, Hiroshima University, Hiroshima, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Ide
authors.affiliation: Gastroenterological and Transplant Surgery, Institute of Biomedical & Health Sciences, Hiroshima University, Hiroshima, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Ohira
authors.affiliation: Gastroenterological and Transplant Surgery, Institute of Biomedical & Health Sciences, Hiroshima University, Hiroshima, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Tahara
authors.affiliation: Gastroenterological and Transplant Surgery, Institute of Biomedical & Health Sciences, Hiroshima University, Hiroshima, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Shimizu
authors.affiliation: Gastroenterological and Transplant Surgery, Institute of Biomedical & Health Sciences, Hiroshima University, Hiroshima, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Saeki
authors.affiliation: Gastroenterological and Transplant Surgery, Institute of Biomedical & Health Sciences, Hiroshima University, Hiroshima, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Sakai
authors.affiliation: Gastroenterological and Transplant Surgery, Institute of Biomedical & Health Sciences, Hiroshima University, Hiroshima, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Yano
authors.affiliation: Gastroenterological and Transplant Surgery, Institute of Biomedical & Health Sciences, Hiroshima University, Hiroshima, Japan. Electronic address: hohdan@hiroshima-u.ac.jp.
authors.forename: H
authors.initials: H
authors.lastname: Ohdan
mesh_terms: D000328:Adult; D058625:End Stage Liver Disease / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology*; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged