Neutrophils: driving progression and poor prognosis in hepatocellular carcinoma?

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Abstract
Irrespective of the underlying aetiology, 90% of hepatocellular carcinomas arise and progress on a background of chronic inflammation. We have explored the independent prognostic value of circulating inflammatory cells. Peripheral blood count data sets from 583 consecutive patients presenting to a single UK centre (2000–2010) were analysed for associations with tumour stage, liver function, performance status (PST) and survival. Validation was in an independent Hong Kong cohort (585 patients; 2007–2013). In both UK and Hong Kong cohorts, neutrophils, platelets, lymphocytes, the neutrophil/lymphocyte ratio (NLR) and the Systemic Immune-Inflammation Index (SII) correlated stepwise, either increasing or decreasing (lymphocytes), with tumour node metastasis (TNM) and Childs–Pugh stage, PST and consequently with the combined Barcelona Clinic for Liver Cancer stage. Survival analyses confirmed the NLR and SII as highly significant prognostic biomarkers. Focused on individual cell types, only the neutrophil count was independently associated with both TNM stage and PST, as well as being significantly and independently associated with poorer survival. In this study of 1168 patients, neutrophils alone, rather than lymphocytes or platelets, were independently associated with outcome. These data support further characterisation of a potentially distinctive role for neutrophils as facilitators of tumour progression and deteriorating performance.

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