Negative Impact of Neutrophil-Lymphocyte Ratio on Outcome After Liver Transplantation for Hepatocellular Carcinoma

Abstract

In Brief Background: The Milan criteria have been adopted by United Network for Organ Sharing (UNOS) to preoperatively assess outcome in patients with hepatocellular carcinoma (HCC) who receive orthotopic liver transplantation (OLT). These criteria rely solely on radiographic appearances of the tumor, providing no measure of tumor biology. Recurrence rates, therefore, remain around 20% for patients within the criteria. The neutrophil-lymphocyte ratio (NLR) is an indicator of inflammatory status previously established as a prognostic indicator in colorectal liver metastases. We aimed to determine whether NLR predicts outcome in patients undergoing OLT for HCC. Design: Analysis of patients undergoing OLT for HCC between 2001 and 2007 at our institution. A NLR ≥5 was considered to be elevated. Results: A total of 150 patients were identified, with 13 patients having an elevated NLR. Of these, 62% developed recurrence compared with 14% with normal NLR (P < 0.0001). The disease-free survival for patients with high NLR was significantly worse than that for patients with normal NLR (1-, 3-, and 5-year survivals of 38%, 25%, and 25% vs. 92%, 85%, and 75%, P < 0.0001). Patients with high NLR also had poorer overall survival (5-year survival, 28% vs. 64%, P = 0.001). Patients within Milan with an elevated NLR had significantly poorer disease-free survival than those with normal NLR within Milan (5-year survival, 30% vs. 81%, P < 0.0001). On univariate analysis, 9 factors including an NLR ≥5 were significant predictors of poor disease-free survival. However, only a raised NLR remained significant on multivariate analysis (P = 0.005, HR: 19.98). Conclusion: Elevated NLR significantly increases the risk for tumor recurrence and recipient death. Preoperative NLR measurement may provide a simple method of identifying patients with poorer prognosis and act as an adjunct to Milan in determining, which patients benefit most from OLT. The Milan criteria assess which patients with hepatocellular carcinoma should receive liver transplants. There remains debate as to the utility of these criteria in predicting outcome as they do not include tumor biology measures. We present a novel method of preoperatively assessing outcome in patients with hepatocellular carcinoma who undergo liver transplants, using the neutrophil-lymphocyte ratio. This may act as an important adjunct to these criteria in the future.