title: Neutrophil-lymphocyte ratio reflects hepatocellular carcinoma recurrence after liver transplantation via inflammatory microenvironment.
abstract: OBJECTIVE
  Although the Milan criteria (MC) have been used to select liver transplantation candidates among patients with hepatocellular carcinoma (HCC), many patients exceeding the MC have shown good prognosis. Preoperative neutrophil-lymphocyte ratio (NLR) is a predictor of patient prognosis, but its mechanism has never been clarified.
  
  
  METHODS
  We assessed outcomes in 158 patients who had undergone living-donor liver transplantation (LDLT) for HCC. Recurrence-free survival (RFS) was determined in patients with high (≥ 4) and low (<4) NLR. Levels of expression of vascular endothelial growth factor (VEGF), interleukin (IL)-8, IL-17, CD68, and CD163 were measured.
  
  
  RESULTS
  The 5-year RFS rate was significantly lower in patients with high (n=26) than with low (n=132) NLR (30.3% vs. 89.0%, p<0.0001), in patients with high (n=15) than with low (n=79) NLR who met the MC (73.6% vs. 100%, p=0.0008) and in patients with high (n=11) than with low (n=53) NLR who exceeded the MC (0% vs. 76.1%, p=0.0002). Tumor expression of VEGF, IL8, IL-17, CD68, and CD163 was similar in the high and low NLR groups, but serum and peritumoral IL-17 levels were significantly higher in the high-NLR group (p=0.01 each). The density of peritumoral CD163 correlated with the density of peritumoral IL-17-producing cells (p=0.04) and was significantly higher in the high-NLR group (p=0.005).
  
  
  CONCLUSIONS
  NLR predicts outcomes after LDLT for HCC via the inflammatory tumor microenvironment. Combined with the MC, NLR may be a new criterion for LDLT candidates with HCC.
authors.affiliation: Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Motomura
authors.forename: Ken
authors.initials: K
authors.lastname: Shirabe
authors.forename: Yohei
authors.initials: Y
authors.lastname: Mano
authors.forename: Jun
authors.initials: J
authors.lastname: Muto
authors.forename: Takeo
authors.initials: T
authors.lastname: Toshima
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Umemoto
authors.forename: Takasuke
authors.initials: T
authors.lastname: Fukuhara
authors.forename: Hideaki
authors.initials: H
authors.lastname: Uchiyama
authors.forename: Toru
authors.initials: T
authors.lastname: Ikegami
authors.forename: Tomoharu
authors.initials: T
authors.lastname: Yoshizumi
authors.forename: Yuji
authors.initials: Y
authors.lastname: Soejima
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Maehara
mesh_terms: D000328:Adult; D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000276:immunology / Q000401:mortality / Q000601:surgery; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D020381:Interleukin-17 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D053208:Kaplan-Meier Estimate; D008113:Liver Neoplasms / Q000276:immunology / Q000401:mortality / Q000601:surgery; D016031:Liver Transplantation / Q000401:mortality*; D018655:Lymphocyte Count; D008214:Lymphocytes / Q000166:cytology*; D008264:Macrophages / Q000166:cytology; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000276:immunology* / Q000401:mortality; D009504:Neutrophils / Q000166:cytology*; D011237:Predictive Value of Tests; D011300:Preoperative Care; D011379:Prognosis; D012307:Risk Factors; D059016:Tumor Microenvironment / Q000276:immunology; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D055815:Young Adult
chemical_list: C508606:CXCL8 protein, human; D020381:Interleukin-17; D016209:Interleukin-8; D042461:Vascular Endothelial Growth Factor A