T. Motomura1, T. Yoshizumi1, A. Nagatsu1, S. Itoh1, N. Harada1, N. Harimoto1, T. Ikegami1, Y. Soejima1, Y. Maehara1 1Kyushu University,Department Of Surgery And Sciences,Fukuoka, , Japan
Introduction:
Although the Milan criteria (MC) have been used to select liver transplantation candidates among patients with hepatocellular carcinoma (HCC), many patients exceeding the MC have shown good prognosis. Recently, inflammation-based scores such as Preoperative neutrophil–lymphocyte ratio (NLR) or platelet-lymphocyte ratio (PLR) are received attention as predictors of patient prognosis in various malignant cancers, but it has yet to be clarified which is better criteria for liver transplantation with HCC.
Methods:
We assessed outcomes in 202 patients who had undergone living-donor liver transplantation (LDLT) for HCC (1999.Jul-2015.Sep). Recurrence-free survival (RFS) was determined in patients with high (≥4) and low (<4) NLR, or with high (≥150) and low (<150) PLR. The cut-off values were determined according to the previous reports. Next, the levels of expression of vascular endothelial growth factor (VEGF), interleukin (IL)-8, IL-17, CD68 and CD163 were measured.
Results:
The 5-year RFS rate was significantly lower in patients with high (n=29) than with low (n=172) NLR (52.8% versus 88.9%, P<0.0001), both in patients with high (n=17) than with low (n=185) PLR (55.9% versus 86.8%, P<0.05). Multivariate analysis showed both NLR and MC significantly correlated with HCC recurrence (p=0.0009 and p=0.0001, respectively), whereas PLR was not significant (p=0.71). Combined with NLR and MC, the 5-year RFS rate was significantly lower in patients with high (n=11) than with low (n=57) NLR who exceeded the MC (19.5% versus 76.8%, P=0.0002). Tumor expression of VEGF, IL8, IL-17, CD68 and CD163 was similar in the high and low NLR groups, but serum and peritumoral IL-17 were significantly higher in the high-NLR group (P=0.01 each). The peritumoral CD163 correlated with the peritumoral IL-17-producing cells (P=0.04) and was significantly higher in the high-NLR group (P=0.005).
Conclusion:
NLR predicts outcomes after LDLT for HCC via inflammatory tumor microenvironment. Combined with the MC, NLR may be a new criterion for LDLT candidates with HCC.