American Journal of Clinical Medicine Research. 2019, 7(1), 1-8
DOI: 10.12691/AJCMR-7-1-1
Original Research

Neutrophil to Lymphocyte Ratio as Predictive Marker of Recurrence of HCC after Radiofrequency Ablation

Eman M. Abdel Rahman1, Fatma M. EL-Senosy1, , Ayman Alsebaey2 and Shiamaa A. Hussien1

1Department of internal medicine, faculty of Medicine (Girls), Al Azher University, Cairo, Egypt

2Department of gastroenterology and Hepatology, Theodor Bilharz Research Institute, Cairo, Egypt

Pub. Date: January 10, 2019

Cite this paper

Eman M. Abdel Rahman, Fatma M. EL-Senosy, Ayman Alsebaey and Shiamaa A. Hussien. Neutrophil to Lymphocyte Ratio as Predictive Marker of Recurrence of HCC after Radiofrequency Ablation. American Journal of Clinical Medicine Research. 2019; 7(1):1-8. doi: 10.12691/AJCMR-7-1-1

Abstract

Background: Neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), and prognostic nutritional index (PNI), are immunonutritional indices, have been shown as an independent factor to predict postoperative recurrence and/or overall survival in patients with hepatocellular carcinoma (HCC). Aim: to validate neutrophils-to-lymphocytes ratio (NLR) as a predictor of post radiofrequency ablation recurrence of hepatocellular carcinoma (HCC). Patients and methods: This cross sectional prospective study was conducted on 50 Egyptian patients had radiofrequency ablation for HCC within Barcelona clinical liver cancer (BCLC) stage A. Pre-treatment laboratory tests and imaging were used to measure NLR, PLR, PNI, Child-Pugh (CTP score, tumor number and tumor size. HCC recurrences were followed after three month. Results: According to NLR cut-off value, the patients with NLR >1.73 had larger tumour size, and higher rates of tumor multiplicity .After 3 month follow up 30/50 (60%) patients had tumour recurrence. Regarding recurrence after RFA showed that CTP class B (P<0.05), tumor size (P<0.05), higher rates of tumor multiplicity (P<0.05), decrease PNI (P<0.001) and increased NLR (P<0.05) after RFA and at baseline were found to be worse prognosis. A receiver-operating characteristic (ROC) analysis was used to classify patients as follows: NLR-PNI 0 group (NLR≤1.73 and PNI > 11.74), NLR-PNI 1 group (NLR > 1.73 or PNI ≤ 11.74) and NLR-PNI 2 group (NLR > 1.73 and PNI ≤ 11.74). The patients with NLR-PNI 2 group had increase in number of portahepatis lymph node, number and size of tumor, decrease serum albumin and change in PNLR. Multivariate analyses suggested increased NLR (hazard ratio [HR] =2.09; 95% confidence interval [CI] =1.88–2.55; P<0.05), increased PLR (HR=0.07; 95% CI=0.06–0.08; P<0.05), and increased AFP (HR=59.20; 95% CI=-99.74–638.78; P<0.05) contributed to post-RFA mortality. Conclusion: High blood NLR after RFA is a predictor for worse survival and also can predict recurrence of HCC. Higher NLR-PNI score predict a worse prognosis in patients who underwent RFA.

Keywords

hepatocellular carcinoma, Radio Frequency Ablation (RFA), neutrophil to lymphocyte ratio

Copyright

Creative CommonsThis work is licensed under a Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/

References

[1]  White DL, Thrift AP, Kanwal F, Davila J, El-Serag HB. Incidence of hepatocellular carcinoma in all 50 United States, from 2000 through 2012. Gastroenterology 2017; 152: 812-820, e5.
 
[2]  Hao-Chien Hung, Jin-Chiao Lee, Chih-Hsien Cheng, Tsung-Han Wu, Yu-Chao Wang, Chen-Fang Lee, et al. (2017). Impact of neutrophil to lymphocyte ratio on survival for hepatocellular carcinoma after curative resection, J Hepatobiliary Pancreat Sci 24:559-569.
 
[3]  She WH, Cheung TT, Jenkins CR, et al. (2016). Clinical applications of high-intensity focused ultrasound. Hong Kong Medical Journal. Aug; 22(4):382-92.
 
[4]  Lü MD, Kuang M, Liang LJ, Xie XY, Peng BG, Liu GJ, Li DM, Lai JM and Li SQ. Surgical resection versus percutaneous thermal ablation for earlystage hepatocellular carcinoma: A randomized clinical trial. Zhonghua Yi Xue Za Zhi 86: 801-805, 2006 (In Chinese).
 
[5]  Chen MS, Li JQ, Zheng Y, Guo RP, Liang HH, Zhang YQ, Lin XJ and Lau WY. A prospective randomized trial comparing percutaneous local ablative therapy and partial hepatectomy for small hepatocellular carcinoma. Ann Surg 243: 321-328, 2006.
 
[6]  Livraghi T, Meloni F, Di Stasi M, Rolle E, Solbiati L, Tinelli C and Rossi S. Sustained complete response and complications rates after radiofrequency ablation of very early hepatocellular carcinoma in cirrhosis: Is resection still the treatment of choice? Hepatology 47: 82-89, 2008.
 
[7]  Kao WY, Chiou YY, Hung HH, Chou YH, Su CW, Wu JC, Huo TI, Huang YH, Lin HC and Lee SD. Risk factors for long-term prognosis in hepatocellular carcinoma after radiofrequency ablation therapy: The clinical implication of aspartate aminotransferaseplatelet ratio index. Eur J Gastroenterol Hepatol 23: 528-536, 2011.
 
[8]  Dan J, Zhang Y, Peng Z, et al. (2013). Postoperative neutrophil-to lymphocyte ratio change predicts survival of patients with small hepatocellular carcinoma undergoing radiofrequency ablation. PLoS One. 8: e58184.
 
[9]  Chan AW, Chan SL,Wong GL, et al. (2015). Prognostic Nutritional Index (PNI) predicts tumor recurrence of very early/early stage hepatocellular carcinoma after surgical resection. Ann Surg Oncol. 22: 41: 38-48.
 
[10]  Motomura T, Shirabe K, Mano Y, et al. (2013). Neutrophil-lymphocyte ratio reflects hepatocellular carcinoma recurrence after liver transplantation via inflammatory microenvironment. J Hepatol. 58(1): 58-64.
 
[11]  Bruix J and Sherman M (2011): Management of Hepatocellular Carcinoma: An update. American Association for the Study of Liver Diseases (AASLD) practice guideline. Hepatol; 53(3): 1020-1022.
 
[12]  Cholongitas E, Papatheodoridis GV, Vangeli M, et al. (2005). "Systematic review: The model for end-stage liver disease--should it replace Child-Pugh's classification for assessing prognosis in cirrhosis?". Aliment Pharmacol Ther; 22: 1079-1089.
 
[13]  Liovet JM, Bustamante J, Castells A, et al. (1999). Natural history of untreated nonsurgical hepatocellular carcinoma: rationale for the design and evaluation of therapeutic trials. Hepatology; 29: 62-67.
 
[14]  Xiao, G. Q., Liu, C., Liu, D. L., Yang, J. Y. & Yan, L. N. Neutrophil-lymphocyte ratio predicts the prognosis of patients with hepatocellular carcinoma after liver transplantation. World J Gastroenterol. 19, 8398-8407 (2013).
 
[15]  Onodera, T., Goseki, N. & Kosaki, G. [Prognostic nutritional index in gastrointestinal surgery of malnourished cancer patients]. Nihon Geka Gakkai Zasshi. 85, 1001-1005 (1984).
 
[16]  Le PH, Liang KH, Chang ML, et al. (2017). Clinical Predictors for Neutrophil–to–Lymphocyte Ratio Changes in Patients with Chronic Hepatitis B Receiving Peginterferon Treatment. in vivo; 31(4): 723-9.
 
[17]  Xiao WK, Chen D, Li SQ, et al. (2014). Prognostic significance of neutrophillymphocyte ratio in hepatocellular carcinoma: a meta-analysis. BMC Cancer. 14:117.
 
[18]  Chen TM, Lin CC, Huang PT, Wen CF (2012). Neutrophil-to-lymphocyte ratio associated with mortality in early hepatocellular carcinoma patients after radiofrequency ablation. J Gastroenterol Hepatol. 27:553-61.
 
[19]  Budhu A, Forgues M, Ye QH, et al. (2006). Prediction of venous metastases, recurrence, and prognosis in hepatocellular carcinoma based on a unique immune response signature of the liver microenvironment. Cancer Cell 10(2): 99-111.
 
[20]  Chien HC, Lee JC, Cheng CH, et al. (2017). Impact of neutrophil to lymphocyte ratio on survival for hepatocellular carcinoma after curative resection. Journal of Hepato-biliary-pancreatic Sciences; 24(10): 559-69.
 
[21]  Jin C, Li C, Peng W, et al. (2017). Changes of platelet times neutrophil to lymphocyte ratio predict BCLC stage A hepatocellular carcinoma survival. Medicine; 96(33).
 
[22]  Tsunematsu S, Suda G, Yamasaki K, et al. (2017). Combination of neutrophil-to-lymphocyte ratio and early des-γ-carboxyprothrombin change ratio as a useful predictor of treatment response for hepatic arterial infusion chemotherapy against advanced hepatocellular carcinoma. Hepatology Research; 47(6):533-41.
 
[23]  Li J, Liao Y, Suo L, et al. (2017). A novel prognostic index—neutrophil times γ-glutamyl transpeptidase to lymphocyte ratio (NγLR) predicts outcome for patients with hepatocellular carcinoma. Scientific Reports; 7(1): 9229.
 
[24]  Chen Q, Dai Z, Yin D, et al. (2015). Negative impact of preoperative platelet lymphocyte ratio on outcome after hepatic resection for intrahepatic cholangiocarcinoma. Medicine (Baltimore); 94: e574.
 
[25]  Pinato DJ, North BV, Sharma R (2012). A novel, externally validated inflammation-based prognostic algorithm in hepatocellular carcinoma: the prognostic nutritional index (PNI). British journal of cancer. 106(8):1439.
 
[26]  Liu C, Li L, Lu WS, et al. (2017). Neutrophil-lymphocyte ratio plus prognostic nutritional index predicts the outcomes of patients with unresectable hepatocellular carcinoma after transarterial chemoembolization. Scientific Reports; Oct 24; 7(1): 13873.
 
[27]  Okamura Y, Sugiura T, Ito T, et al. (2017): The optimal cut-off value of the preoperative prognostic nutritional index for the survival differs according to the TNM stage in hepatocellular carcinoma. Surgery Today, 47(8): 986-993.
 
[28]  Bertuzzo VR, Cescon M, Odaldi F, et al. (2017). Actual risk of using very aged donors for unselected liver transplant candidates. Annals of Surgery; 265(2):388-96.