Prognostic Significance of the Neutrophil-to-Lymphocyte Ratio in Primary Liver Cancer: A Meta-Analysis

<div><p>The neutrophil-to-lymphocyte ratio (NLR) is a useful biomarker that reflects systemic inflammation responses. However, the prognostic value of the NLR in patients with primary liver cancer (PLC) remains controversial. We performed a meta-analysis of 26 studies (comprising 4,461 patients) to evaluate the association between the pre-treatment NLR and clinical outcomes of overall survival (OS) and disease-free survival (DFS) in patients with PLC. The correlation between NLR and tumor characteristics or other inflammation-related parameters was also assessed. Data were synthesized using the random-effects model of DerSimonian and Laird, and the hazard ratio (HR) or odds ratio (OR) with 95% confidence interval (CI) was used to estimate effect size. Our analysis indicated that a high NLR predicted poor OS (HR, 2.102; 95% CI: 1.741–2.538) and DFS (HR, 2.474; 95% CI: 1.855–3.300) for PLC. A high NLR was associated with the presence of tumor vascular invasion (OR: 1.889, 95% CI: 1.487–2.400; <i>p</i><0.001) and an elevated alpha-fetoprotein level (OR: 1.536; 95% CI: 1.152–2.048; <i>p</i> = 0.003). Thus, we conclude that a high NLR indicates a poor prognosis for patients with PLC and may also be predictive for PLC invasion and metastasis. Subgroup analysis suggested that the predictive role of NLR in cholangiocarcinoma is limited, and a further large study to confirm these findings is warranted.</p></div

Stratified forest plots of the association between the NLR and OS.

<p>(A) Subgroup analysis in patients who received different treatments. (B) Subgroup analysis in studies with an NLR cut-off value less than or greater than 5. (C) Subgroup analysis was based on the region in which the study was reported, including 13 Eastern studies and 8 Western studies. Green represents the subgroup pooled effective size, whereas red represents the overall pooled effective size. NLR  =  neutrophil-to-lymphocyte ratio; OS  =  overall survival; CI  =  confidence interval; TL  =  transplantation; *, the different study by Pinato.</p

Forest plots of the association between the NLR and survival of patients with primary liver cancer.

<p>A random-effects model was used. (A) Forest plot of the association between the NLR and OS of 21 studies. (B) Forest plot of the association between the NLR and DFS of 17 studies. Blue represents the HR estimate of each study, whereas red represents the overall pooled effective size. NLR  =  neutrophil-to-lymphocyte ratio; OS  =  overall survival; DFS  =  disease-free survival; *, the different study by Gomez; **, the different study by Wang.</p

Search flow diagram for studies included in the meta-analysis.

<p>Search flow diagram for studies included in the meta-analysis.</p

Baseline characteristics of the twenty-six studies included in the meta-analysis.

<p>*, included 3 ICC; NLR, neutrophil-to-lymphocyte ratio; NOS, Newcastle–Ottawa Scale; NP, not reported; OS, overall survival; DFS, disease-free survival.</p

Forest plots of the association between the NLR and tumor characteristics.

<p>(A) The association between the NLR and vascular invasion. (B) The association between the NLR and an elevated AFP level. Green represents the subgroup pooled effective size, whereas red represents the overall pooled effective size. NLR  =  neutrophil-to-lymphocyte ratio; AFP  =  alpha feto-protein; CI  =  confidence interval; *, the different study by Gomez; **, the different study by Wang.</p

Meta-regression between the NLR cut-off value and lnhr.

<p>NLR  =  neutrophil-to-lymphocyte ratio; lnhr  =  log of the hazard ratio.</p