Prognostication of inflammatory cells in liver transplantation: Is the waitlist neutrophil-to-lymphocyte ratio really predictive of tumor biology?

OBJECTIVE: The objective of this retrospective study was to characterize the neutrophil to lymphocyte ratio (NLR) on the waitlist and determine its prognostic utility in liver transplantation (LT) for hepatocellular carcinoma (HCC) with special focus on longitudinal data. Biomarkers such as pre-operative NLR have been suggested to predict poor oncological outcomes for patients with HCC seeking LT. NLR's utility is thought to be related to tumor biology. However, recent studies have demonstrated that a high NLR conveys worse outcomes in non-HCC cirrhotics. This study investigated the relationship between NLR, liver function, tumor factors and patient prognosis. METHODS: Patients with HCC undergoing LT were identified between 2002 and 2014 (n = 422). Variables of interest were collected longitudinally from time of listing until LT. The prognostic utility of NLR was assessed using Kaplan-Meier and Cox Proportional Hazard regression. Associations between NLR and MELD-Na, AFP, and tumor morphology were also assessed. RESULTS: NLR demonstrated a positive correlation with MELD-Na at LT (R2 = 0.125, P < 0.001) and had parallel trends over time. The lowest NLR quartile had a median MELD-Na of 9 while the highest had a median MELD-Na of 19. There were minimal differences in AFP, tumor morphology, and rates of vascular invasion between quartiles. NLR was a statistically significant predictor of OS (HR = 1.64, P = 0.017) and recurrence (HR = 1.59, P = 0.016) even after controlling for important tumor factors. However, NLR lost its statistical significance when MELD-Na was added to the Cox regression model (OS: HR = 1.46, P = 0.098) (recurrence: HR = 1.40, P = 0.115). CONCLUSIONS: NLR is a highly volatile marker on the waitlist that demonstrates a significant correlation and collinearity with MELD-Na temporally and at the time of LT. These characteristics of NLR bring into question its utility as a predictive marker in HCC patients.