Neutrophil-lymphocyte ratio reflects hepatocellular carcinoma recurrence after liver transplantation via inflammatory microenvironment

J Hepatol. 2013 Jan;58(1):58-64. doi: 10.1016/j.jhep.2012.08.017. Epub 2012 Aug 25.


Background & aims: 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.

MeSH terms

  • Adult
  • Aged
  • Carcinoma, Hepatocellular* / immunology
  • Carcinoma, Hepatocellular* / mortality
  • Carcinoma, Hepatocellular* / surgery
  • Disease-Free Survival
  • Female
  • Humans
  • Interleukin-17 / metabolism
  • Interleukin-8 / metabolism
  • Kaplan-Meier Estimate
  • Liver Neoplasms* / immunology
  • Liver Neoplasms* / mortality
  • Liver Neoplasms* / surgery
  • Liver Transplantation / mortality*
  • Lymphocyte Count
  • Lymphocytes / cytology*
  • Macrophages / cytology
  • Male
  • Middle Aged
  • Neoplasm Recurrence, Local / immunology*
  • Neoplasm Recurrence, Local / mortality
  • Neutrophils / cytology*
  • Predictive Value of Tests
  • Preoperative Care
  • Prognosis
  • Risk Factors
  • Tumor Microenvironment / immunology
  • Vascular Endothelial Growth Factor A / metabolism
  • Young Adult


  • CXCL8 protein, human
  • Interleukin-17
  • Interleukin-8
  • Vascular Endothelial Growth Factor A