Blood neutrophil-to-lymphocyte ratio (NLR) is one index representing systemic inflammation, and high preoperative NLR has been suggested as an independent prognostic factor in HCC. However, the NLR cutoff value with the highest prognostic significance is not consistent, and the mechanism of this phenomenon remains unclear. Preoperative NLR was calculated from complete blood counts obtained before 14 days from operation day in 234 patients who underwent curative resection for primary HCC. The presence of tumor necrosis and degree of tumor-infiltrating lymphocytes (TILs) was determined histologically. High preoperative NLR (≥ 2.5) was observed in 28 (12.0%) of 234 HCCs and was significantly associated with younger age, larger tumor size, high Edmonson grade, microvascular invasion, major portal invasion, advanced AJCC T or BCLC stage, and low albumin level. Patients with high preoperative NLR showed shorter disease-specific survival (DSS) (p = 0.002) and a tendency for shorter recurrence-free survival (RFS) (p = 0.096). High preoperative NLR was associated with presence of tumor necrosis and low TIL. On multivariable analysis, preoperative NLR was an independent prognostic factor for DSS (hazard ratio: 2.050 (95% confidence interval 1.139-3.691), p = 0.017). However, the independent prognostic effect of NLR for DSS disappeared when tumor necrosis and TILs were added as co-variables. High NLR is an independent prognostic factor in patients with HCC who undergo curative resection. The prognostic effect of high NLR might originate from the prognostic effect of tumor necrosis or TILs.
Keywords: Hepatocellular carcinoma; Necrosis; Neutrophil to lymphocyte ratio; Prognosis; Systemic inflammation; Tumor-infiltrating lymphocytes.