A scoring model based on neutrophil to lymphocyte ratio predicts recurrence of HBV-associated hepatocellular carcinoma after liver transplantation

Abstract

Background: Neutrophil to lymphocyte ratio (NLR) has been proposed to predict prognosis of hepatocellular carcinoma (HCC). However, the cut-off values are empirical. We determined the optimal cut-off value to predict HCC recurrence after liver transplantation (LT) and further established a scoring model based on NLR.

Methodology/principal findings: We analyzed the outcome of 101 HBV-associated HCC patients undergoing LT. Preoperative risk factors for tumor recurrence were evaluated by univariate analysis. By using ROC analysis, NLR≥3 was considered elevated. The disease-free survival (DFS) and overall survival (OS) for patients with high NLR was significantly worse than that for patients with normal NLR (the 5-year DFS and OS of 28.5% and 19.5% vs. 64.9% and 61.8%, respectively; P<0.001). Univariate analysis revealed that tumor size >5 cm, tumor number >3, macrovascular invasion, AFP≥400 µg/L, NLR≥3, and HBV-DNA level >5 log10 copies/mL were preoperative predictors of DFS. Cox regression analysis showed macrovascular invasion, tumor number, and high NLR were independent prognostic factors. We then established a preoperative prognostic score based on multivariate analysis. Each factor was given a score of 1. Area under the ROC curve of the score was 0.781. All nine patients with score 3 developed recurrence within 6 months after LT. Of 71 patients without vascular invasion, three patients with both tumor number >3 and NLR≥3 developed recurrence within 14 months after LT while the 5-year DFS and OS for patients with a score of 0 or 1 were 68.1% and 62.8%, respectively.

Conclusions/significance: Preoperative elevated NLR significantly increases the risk of recurrence in patients underwent LT for HCC. Patients with both NLR≥3 and tumor number >3 are not a good indication for LT. Our score model may aid in the selection of patients that would most benefit from transplantation for HCC.

Figure 1. Kaplan-Meier survival curves for patients with high or normal NLR.

There was a significant difference in DFS and OS between patients with low and high NLR. The 5-yr DFS (A) and OS (B) for patients with normal or high NLR were 64.9%, 28.5%, and 61.8%, 19.5%, respectively (both P<0.001).

Figure 2. Disease-free survival for patients classified according to NLR and the different criteria.

(A) The Kaplan-Meier curves for patients classified according to the Milan, UCSF and HangZhou criteria showed patients within Milan had significantly better DFS than patients outside UCSF but within HangZhou criteria (log rank test, P = 0.001). (B) Among patients beyond Milan criteria, a significant difference in DFS existed between patients with normal and elevated NLR (log rank test, P = 0.015).

Figure 3. Disease-free survival for patients classified according to the preoperative prognostic score.

(A) The Kaplan-Meier curves showed there was a significant difference in DFS among four groups of patients with score 0 to 3. (B) A significant difference in DFS existed when patients were reclassified into two groups (score 0 or 1, and 2 or 3).

Figure 4. The prognostic value of the preoperative prognostic score model for patients without vascular invasion.

The Kaplan-Meier curves showed there was a significant difference in DFS (A) and OS (B) between patients with a score of 2 and patients with a score of 0 or 1.