Background/Aims Inflammation-based scores, such as the neutrophil-to-lymphocyte ratio (NLR), have been associated with prognosis in hepatocellular carcinoma (HCC); but variable cut-off values and potential lack of specificity have limited the utility of NLR. This study evaluates NLR in a large cohort of HCC patients.
Methods We retrospectively reviewed 789 HCC cases (1993–2017) for demographics, tumor characteristics, treatment, and survival. NLR was stratified into NLR ≥1.5 and NLR ≥3 and analyzed for correlation with American Joint Committee on Cancer (AJCC) and Barcelona Clinic Liver Cancer (BCLC) stages. In 235 patients who underwent liver resection, survival and recurrence were evaluated by NLR.
Results In 789 HCC cases, mean NLR was increased with advanced AJCC and BCLC stages. Hepatitis C patients were less likely to have NLR ≥1.5 and ≥3. Non-alcoholic steatohepatitis patients were more likely to have NLR ≥3. Patients with tumor size >5 cm, rupture, or macrovascular invasion were more likely to have NLR ≥3. In patients treated with resection, NLR ≥3 predicted early recurrence (odds ratio [OR] 4.14, P<0.01) and overall recurrence (OR 4.05, P<0.01). Mean NLR was 4.30 in those with recurrence and 2.75 in those without recurrence. Patients with NLR ≥3 showed significantly worse survival compared to those with NLR <3 (P<0.01 by log-rank test).
Conclusions Elevated NLR is associated with advanced cancer stage and aggressive tumor characteristics, such as large size, rupture, and invasion. NLR ≥3 was associated with early and overall recurrence after resection but varied with etiology. NLR may be a useful biomarker in predicting recurrence for HCC patients undergoing curative resection, but further studies are required to elucidate the effect of disease etiology.
Citations
Citations to this article as recorded by
Establishment and Validation of a Nomogram Based on Inflammation-Immunity-Nutrition Biomarker Scores to Predict Postoperative Early Recurrence in Patients with Hepatocellular Carcinoma: A Multicenter Study Yuhan Zhang, Jin Tang, Yan Liu, Limei Tao, Zhiying Liu, Kexi Liao, Qiaoying Yuan Journal of Hepatocellular Carcinoma.2026; Volume 13: 1. CrossRef
Response to the Letter on “Role of ALBI Grade as a Predictive Factor for Long‐Term Mortality in Patients With Hepatocellular Carcinoma (HCC) Undergoing Transarterial Chemoembolization (TACE)” Kyoung A Ko, Won Sohn Journal of Gastroenterology and Hepatology.2026; 41(3): 1101. CrossRef
SPP1+ neutrophil and exhausted CD8⁺ T cells infiltration predicting the early recurrence of hepatocellular carcinoma patients after R0 resection Kai Luo, Tao Song, Xin Zheng, Cheng Guo, Shaoshan Han International Journal of Surgery.2026; 112(5): 11563. CrossRef
Hepatic immune prognostic index as a prognostic biomarker in hepatocellular carcinoma patients treated with transarterial chemoembolization Jing Li, Yi Ren, Guilin Zhang, Yusheng Guo, Suyue Wu, Weimin Zhao, Chuansheng Zheng, Lian Yang, Xuefeng Kan Therapeutic Advances in Medical Oncology.2026;[Epub] CrossRef
Prognostic impact of CT-derived sarcopenic obesity in solitary hepatocellular carcinoma after hepatectomy: Does the definition matter? Qian-Bo Zhang, Xu Lv, Yiying Li, Xiaodie Qu, Gui-Xue Dai, Kai Zhang, Yongping Zhou, Fang-Ming Chen European Journal of Surgical Oncology.2026; 52(9): 111975. CrossRef
Baseline Tumor-Specific Prognosis in Early-Stage Hepatocellular Carcinoma: Time-Dependent Role of Biomarker Profile and Modified ALBI Grade Kelley Núñez, Juan Gimenez, Ari J. Cohen, Jeffrey Burton, Tyler Sandow, Paul Thevenot Cancers.2026; 18(13): 2073. CrossRef
Triple-negative breast cancer modifies the systemic immune landscape and alters neutrophil functionality Noor A. M. Bakker, Hannah Garner, Ewald van Dyk, Elisa Champanhet, Chris Klaver, Maxime Duijst, Leonie Voorwerk, Iris Nederlof, Rosie Voorthuis, Marte C. Liefaard, Marja Nieuwland, Iris de Rink, Onno B. Bleijerveld, Hendrika M. Oosterkamp, Lodewyk F. A. W npj Breast Cancer.2025;[Epub] CrossRef
Online risk scores for pre- and postoperative prediction of early recurrence in hepatocellular carcinoma patients undergoing conversion liver resection after tyrosine kinase inhibitors and immune checkpoint inhibitors therapy Kong-Ying Lin, Hong-Zhi Liu, Jian-Wei Liu, Xiao-Dong Zhu, Yang-Xun Pan, Shun-Li Shen, Wei Zhang, Ren-An Jin, Chuang-Ye Han, Jie Chen, Xiao-Yun Zhang, Bin-Yong Liang, Yao-Dong Zhang, Jian Ma, Nan-Ya Wang, Dong-Xiao Li, Rui Xiong, Zhong-Chao Li, Jing-Dong L European Journal of Surgical Oncology.2025; 51(9): 110220. CrossRef
Immunosuppressive tumor microenvironment and immunotherapy of hepatocellular carcinoma: current status and prospectives Ke-Yu Shen, Ying Zhu, Sun-Zhe Xie, Lun-Xiu Qin Journal of Hematology & Oncology.2024;[Epub] CrossRef
Establishment and Validation of Nomogram for Predicting Early Postoperative Recurrence of Liver Cancer 永辉 马 Advances in Clinical Medicine.2024; 14(03): 1859. CrossRef
The predictive value of NLR, PLR and MLR in the differential diagnosis of benign uterine diseases and endometrial malignant tumors Lin Qin Discover Oncology.2024;[Epub] CrossRef
Correlation of Prognostic Nutritional Index and Systemic Immune-Inflammation Index with the Recurrence and Prognosis in Oral Squamous Cell Carcinoma with the Stage of III/IV Manjun Ye, Lixia Zhang International Journal of General Medicine.2024; Volume 17: 2289. CrossRef
Hepatocellular Interactions of Potential Nutraceuticals in the Management of Inflammatory NAFLD Devaraj Ezhilarasan, Kulanthaivel Langeswaran Cell Biochemistry and Function.2024;[Epub] CrossRef
Pinpointing the integration of artificial intelligence in liver cancer immune microenvironment Ihtisham Bukhari, Mengxue Li, Guangyuan Li, Jixuan Xu, Pengyuan Zheng, Xiufeng Chu Frontiers in Immunology.2024;[Epub] CrossRef
Immune cells and their derived microRNA-enriched extracellular vesicles in nonalcoholic fatty liver diseases: Novel therapeutic targets Liu Yang, Yawen Hao, Joost Boeckmans, Robim M. Rodrigues, Yong He Pharmacology & Therapeutics.2023; 243: 108353. CrossRef
An Overview of Hepatocellular Carcinoma Surveillance Focusing on Non-Cirrhotic NAFLD Patients: A Challenge for Physicians Annalisa Cespiati, Felice Cinque, Marica Meroni, Rosa Lombardi, Paola Dongiovanni, Anna Ludovica Fracanzani Biomedicines.2023; 11(2): 586. CrossRef
Human microbiomes in cancer development and therapy Chenglai Xia, Jiyan Su, Can Liu, Zhikai Mai, Shuanghong Yin, Chuansheng Yang, Liwu Fu MedComm.2023;[Epub] CrossRef
Prediction model for hepatocellular carcinoma recurrence after hepatectomy: Machine learning-based development and interpretation study Rongqiang Liu, Shinan Wu, Hao yuan Yu, Kaining Zeng, Zhixing Liang, Siqi Li, Yongwei Hu, Yang Yang, Linsen Ye Heliyon.2023; 9(11): e22458. CrossRef
High Neutrophil–Lymphocyte Ratio and Delta Neutrophil–Lymphocyte Ratio Are Associated with Increased Mortality in Patients with Hepatocellular Cancer Nicole E. Rich, Aarthi Parvathaneni, Ahana Sen, Mobolaji Odewole, Ana Arroyo, Arjmand R. Mufti, Thomas A. Kerr, Lafaine Grant, Shannan R. Tujios, Marlyn J. Mayo, William M. Lee, Ju Dong Yang, Takeshi Yokoo, Purva Gopal, Yujin Hoshida, Hao Zhu, Adam C. Yop Digestive Diseases and Sciences.2022; 67(6): 2666. CrossRef
Application of Serum Biomarkers in Early Diagnosis and Prognosis of Hepatocellular Carcinoma 佳骏 芦 Advances in Clinical Medicine.2022; 12(06): 5446. CrossRef
Prognostic Nutritional Index and Neutrophil/Lymphocyte Ratio Can Serve as Independent Predictors of the Prognosis of Hepatocellular Carcinoma Patients Receiving Targeted Therapy Wei Chen, Mingjun Zhang, Chanjuan Chen, Xiaonan Pang, Jinghua Pan Journal of Oncology.2022; 2022: 1. CrossRef
Ficolin-2: A potential immune-related therapeutic target with low expression in liver cancer Li-ting Wang, Qiu-ling Zeng, Shao-lan Jiang, Zhen-yu Chen, Xiao-ling Wang, Ling Li, Xiaolong Li Frontiers in Oncology.2022;[Epub] CrossRef
Usefulness of neutrophil-to-lymphocyte ratio (NLR) as a prognostic predictor after treatment of hepatocellular carcinoma." Review article Mohamad Mouchli, Shravani Reddy, Miranda Gerrard, Lisa Boardman, Marrieth Rubio Annals of Hepatology.2021; 22: 100249. CrossRef
Surgery versus external beam radiotherapy for hepatocellular carcinoma involving the inferior vena cava or right atrium: A systematic review and meta‐analysis Han Ah Lee, Sunmin Park, Yeon Seok Seo, Won Sup Yoon, In‐Soo Shin, Chai Hong Rim Journal of Hepato-Biliary-Pancreatic Sciences.2021; 28(12): 1031. CrossRef
Liver Fibrosis in Non-alcoholic Fatty Liver Disease: From Liver Biopsy to Non-invasive Biomarkers in Diagnosis and Treatment Leen J. M. Heyens, Dana Busschots, Ger H. Koek, Geert Robaeys, Sven Francque Frontiers in Medicine.2021;[Epub] CrossRef
Treatment efficacy by hepatic arterial infusion chemotherapy vs. sorafenib after liver-directed concurrent chemoradiotherapy for advanced hepatocellular carcinoma Sojung Han, Hye Jin Choi, Seung-Hoon Beom, Hye Rim Kim, Hyein Lee, Jae Seung Lee, Hye Won Lee, Jun Yong Park, Seung Up Kim, Do Young Kim, Sang Hoon Ahn, Kwang-Hyub Han, Jinsil Seong, Jong Yun Won, Beom Kyung Kim Journal of Cancer Research and Clinical Oncology.2021; 147(10): 3123. CrossRef
Clinical Characteristics of Long-Term Survivors After Sorafenib Treatment for Unresectable Hepatocellular Carcinoma: A Korean National Multicenter Retrospective Cohort Study Young Youn Cho, Su Jong Yu, Hye Won Lee, Do Young Kim, Wonseok Kang, Yong-Han Paik, Pil Soo Sung, Si Hyun Bae, Su Cheol Park, Young Seok Doh, Kang Mo Kim, Eun Sun Jang, In Hee Kim, Won Kim, Yoon Jun Kim Journal of Hepatocellular Carcinoma.2021; Volume 8: 613. CrossRef
Natural killer cell activity is a risk factor for the recurrence risk after curative treatment of hepatocellular carcinoma Han Ah Lee, Hyun Gil Goh, Young-Sun Lee, Young Kul Jung, Ji Hoon Kim, Hyung Joon Yim, Min-Goo Lee, Hyunggin An, Yoon Tae Jeen, Jong Eun Yeon, Kwan Soo Byun, Yeon Seok Seo BMC Gastroenterology.2021;[Epub] CrossRef
Immunological Markers, Prognostic Factors and Challenges Following Curative Treatments for Hepatocellular Carcinoma Soon Kyu Lee, Sung Won Lee, Jeong Won Jang, Si Hyun Bae, Jong Young Choi, Seung Kew Yoon International Journal of Molecular Sciences.2021; 22(19): 10271. CrossRef
Novel model combining contrast-enhanced ultrasound with serology predicts hepatocellular carcinoma recurrence after hepatectomy Hai-Bin Tu, Li-Hong Chen, Yu-Jie Huang, Si-Yi Feng, Jian-Ling Lin, Yong-Yi Zeng World Journal of Clinical Cases.2021; 9(24): 7009. CrossRef
Cellular based immunotherapy for primary liver cancer Yuanyuan Zheng, Yan Li, Jiao Feng, Jingjing Li, Jie Ji, Liwei Wu, Qiang Yu, Weiqi Dai, Jianye Wu, Yingqun Zhou, Chuanyong Guo Journal of Experimental & Clinical Cancer Research.2021;[Epub] CrossRef
Neutrophil to lymphocyte ratio and albumin bilirubin grade in hepatocellular carcinoma: A systematic review Ayman Bannaga, Ramesh P Arasaradnam World Journal of Gastroenterology.2020; 26(33): 5022. CrossRef
A novel predictive model based on inflammatory markers to assess the prognosis of patients with HBV-related acute-on-chronic liver failure: a retrospective cohort study Li Qiang, Jiao Qin, Changfeng Sun, Yunjian Sheng, Wen Chen, Bangdong Qiu, Xin Chen, Yuanfang Chen, Fei Liu, Gang Wu BMC Gastroenterology.2020;[Epub] CrossRef
First
Prev
