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An elevated neutrophil-to-lymphocyte ratio predicts a poor postoperative survival in primary hepatocellular carcinoma patients with a normal preoperative serum level of alpha-fetoprotein

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Abstract

Purpose

Although alpha-fetoprotein (AFP) is a useful prognostic marker in patients with hepatocellular carcinoma (HCC), a recent study has shown that the preoperative neutrophil-to-lymphocyte ratio (NLR) is also associated with the postoperative survival in such patients.

Objective

To investigate the significance of the NLR in patients with primary HCC (p-HCC) showing a normal preoperative AFP.

Methods

Among 478 p-HCC patients undergoing curative surgery, 112 who had a normal AFP (< 8 ng/ml) were enrolled. The patients were divided into two groups: group A, who did not have an elevated NLR (≤ 3.2); and group B, who had an elevated NLR (> 3.2). Uni- and multivariate analyses were performed to compare clinical features with the overall survival (OS).

Results

A multivariate analysis of the clinical features showed that the NLR (> 3.2/≤ 3.2) (hazard ratio 2.366; 95% CI 1.069–5.235; P = 0.034) was closely associated with the OS, along with the age (> 65/≤ 65 years) (P = 0.033). Group B had a significantly lower survival ratio than group A in terms of not only the OS (P = 0.013), but also the cancer-specific survival (P = 0.002) and relapse-free survival (P = 0.039).

Conclusions

An elevated NLR (> 3.2) is predictive of a poor survival in patients with primary HCC (p-HCC) showing normal AFP levels.

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Abbreviations

AFP:

Alpha-fetoprotein (α-fetoprotein)

ALT:

Alanine aminotransferase

AST:

Aspartate aminotransferase

CH:

Chronic hepatitis

CRP:

C-reactive protein

CSS:

Cancer-specific survival

GPS:

Glasgow Prognostic Score

HBV:

Hepatitis B virus

HCC:

Hepatocellular carcinoma

HCV:

Hepatitis C virus

ICG R15:

Indocyanine green retention ratio at 15 min

NL:

Normal liver

NLR:

Neutrophil-to-lymphocyte ratio

LC:

Liver cirrhosis

OS:

Overall survival

PIVKA II:

Protein induced by vitamin K absence or antagonists II

RFS:

Relapse-free survival

ROC curve:

Receiver operating characteristic curve

SIR:

Systematic inflammatory response

Va:

Hepatic arterial infiltration

Vp:

Portal venous infiltration

Vv:

Hepatic venous infiltration

WBC:

White blood cell

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Correspondence to Mitsuru Ishizuka.

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Supplementary material 1 (DOC 68 KB)

595_2019_1781_MOESM2_ESM.tif

Supplementary Fig. 1. The relationship between the NLR (NLR ≤3.2 and NLR &#x003E;3.2 from top to bottom) and the overall survival in patients undergoing surgery for primary HCC with a preoperative serum level of alpha-fetoprotein &#x003E;8 ng/ml (TIF 178 KB)

595_2019_1781_MOESM3_ESM.tif

Supplementary Fig. 2. The relationship between the NLR (NLR ≤3.2 and NLR &#x003E;3.2 from top to bottom) and the cancer-specific survival in patients undergoing surgery for primary HCC with a preoperative serum level of alpha-fetoprotein &#x003E;8 ng/ml (TIF 145 KB)

595_2019_1781_MOESM4_ESM.tif

Supplementary Fig. 3. The relationship between the NLR (NLR ≤3.2 and NLR &#x003E;3.2 from top to bottom) and the relapse-free survival in patients undergoing surgery for primary HCC with a preoperative serum level of alpha-fetoprotein &#x003E;8 ng/ml (TIF 131 KB)

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Shiraki, T., Ishizuka, M., Kubota, K. et al. An elevated neutrophil-to-lymphocyte ratio predicts a poor postoperative survival in primary hepatocellular carcinoma patients with a normal preoperative serum level of alpha-fetoprotein. Surg Today 49, 661–669 (2019). https://doi.org/10.1007/s00595-019-01781-1

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