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

Takashi Motomura, Ken Shirabe, Yohei Mano, Jun Muto, Takeo Toshima, Yuichiro Umemoto, Takasuke Fukuhara, Hideaki Uchiyama, Toru Ikegami, Tomoharu Yoshizumi, Yuji Soejima, Yoshihiko Maehara

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Abstract

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.

Original languageEnglish
Pages (from-to)58-64
Number of pages7
JournalJournal of Hepatology
Volume58
Issue number1
DOIs
Publication statusPublished - Jan 1 2013

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Liver Transplantation
Hepatocellular Carcinoma
Neutrophils
Lymphocytes
Recurrence
Interleukin-17
Living Donors
Interleukin-8
Vascular Endothelial Growth Factor A
Tumor Microenvironment
Survival Rate
Survival
Serum

All Science Journal Classification (ASJC) codes

  • Hepatology

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Neutrophil-lymphocyte ratio reflects hepatocellular carcinoma recurrence after liver transplantation via inflammatory microenvironment. / Motomura, Takashi; Shirabe, Ken; Mano, Yohei; Muto, Jun; Toshima, Takeo; Umemoto, Yuichiro; Fukuhara, Takasuke; Uchiyama, Hideaki; Ikegami, Toru; Yoshizumi, Tomoharu; Soejima, Yuji; Maehara, Yoshihiko.

In: Journal of Hepatology, Vol. 58, No. 1, 01.01.2013, p. 58-64.

Research output: Contribution to journalArticle

Motomura, T, Shirabe, K, Mano, Y, Muto, J, Toshima, T, Umemoto, Y, Fukuhara, T, Uchiyama, H, Ikegami, T, Yoshizumi, T, Soejima, Y & Maehara, Y 2013, 'Neutrophil-lymphocyte ratio reflects hepatocellular carcinoma recurrence after liver transplantation via inflammatory microenvironment', Journal of Hepatology, vol. 58, no. 1, pp. 58-64. https://doi.org/10.1016/j.jhep.2012.08.017
Motomura, Takashi ; Shirabe, Ken ; Mano, Yohei ; Muto, Jun ; Toshima, Takeo ; Umemoto, Yuichiro ; Fukuhara, Takasuke ; Uchiyama, Hideaki ; Ikegami, Toru ; Yoshizumi, Tomoharu ; Soejima, Yuji ; Maehara, Yoshihiko. / Neutrophil-lymphocyte ratio reflects hepatocellular carcinoma recurrence after liver transplantation via inflammatory microenvironment. In: Journal of Hepatology. 2013 ; Vol. 58, No. 1. pp. 58-64.
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abstract = "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.",
author = "Takashi Motomura and Ken Shirabe and Yohei Mano and Jun Muto and Takeo Toshima and Yuichiro Umemoto and Takasuke Fukuhara and Hideaki Uchiyama and Toru Ikegami and Tomoharu Yoshizumi and Yuji Soejima and Yoshihiko Maehara",
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T1 - Neutrophil-lymphocyte ratio reflects hepatocellular carcinoma recurrence after liver transplantation via inflammatory microenvironment

AU - Motomura, Takashi

AU - Shirabe, Ken

AU - Mano, Yohei

AU - Muto, Jun

AU - Toshima, Takeo

AU - Umemoto, Yuichiro

AU - Fukuhara, Takasuke

AU - Uchiyama, Hideaki

AU - Ikegami, Toru

AU - Yoshizumi, Tomoharu

AU - Soejima, Yuji

AU - Maehara, Yoshihiko

PY - 2013/1/1

Y1 - 2013/1/1

N2 - 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.

AB - 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.

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