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NLR may predict HCC recurrence in liver transplant recipients

Patients with hepatocellular carcinoma who had neutrophil-lymphocyte ratios of 4 or greater after a liver transplant were more likely to experience recurrence in a recent study.

Researchers evaluated 158 patients with hepatocellular carcinoma (HCC) who underwent living donor liver transplantation (LDLT) between July 1999 and March 2011 at a hospital in Fukuoka, Japan. Patients were grouped according to preoperative neutrophil-lymphocyte ratios (NLR) and rates of recurrence-free survival (RFS) following the procedure were calculated. Investigators also measured participants’ expression of vascular endothelial growth factor (VEGF), IL-8, IL-17, CD68 and CD163, during a median follow-up of 40.3 months.

RFS rates for the entire cohort were 90.8% at 1 year, 84.5% at 3 years and 82.7% at 5 years. RFS at all evaluated time points was significantly greater among patients with low NLR (less than 4, n=132) than in those with high NLR (4 or greater, n=26) (P<.0001). An NLR of 4 or greater was associated with HCC recurrence via multivariate analysis (HR=6.24, P=.0002).

Patients with high NLR had significantly greater serum concentration and peritumoral expression of IL-17 compared with those with low NLR (P=.02 for serum and P=.03 for peritumoral), but intratumoral expression was similar between the groups (P=.32). High-NLR patients also had a significantly greater density of peritumoral CD163-positive tumor-assisted macrophage expression (TAMs), and a correlation was observed between peritumoral CD163 TAM density and that of cells producing peritumoral IL-17 (P=.04).

Among patients with high NLR, those who underwent splenectomy had significantly greater RFS rates at all time points than those who did not (P=.02 for difference). No significant difference was observed in RFS rates among patients with low NLR according to splenectomy (P=.63).

“We found that elevated NLR was significantly correlated with HCC recurrence after LDLT via an inflammatory tumor microenvironment provided by TAMs and IL-17-producing cells,” the researchers concluded. “Although investigations involving larger numbers of patients are required, our findings suggest that splenectomy maybe a useful strategy for preventing tumor recurrence after [liver transplant] in HCC patients with high NLR.”