Stratified neutrophil-to-lymphocyte ratio accurately predict mortality risk in hepatocellular carcinoma patients following curative liver resection

Huang, Guiqian; Zhu, Gui‐Qi; Liu, Yanlong; Wang, Liren; Braddock, Martin; Zheng, Ming‐Hua; Zhou, Mengtao

doi:10.18632/oncotarget.6707

Cited by 17 publications

(16 citation statements)

References 42 publications

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“…In the evolution of patients with HCC undergoing radiofrequency ablation, or surgical resection, a high NLR predicted poor outcomes with higher recurrence and mortality rates (74–77) and poor overall survival even after a curative liver resection (76). And even in those undergoing liver transplantation, a high NLR was associated with poorer overall and recurrence-free survival (78).…”

Section: The Role Of Cellular Immune Imbalances In Nafldmentioning

confidence: 99%

Immune Imbalances in Non-Alcoholic Fatty Liver Disease: From General Biomarkers and Neutrophils to Interleukin-17 Axis Activation and New Therapeutic Targets

Paquissi

2016

Front. Immunol.

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Non-alcoholic fatty liver disease (NAFLD) is an increasing problem worldwide and is associated with negative outcomes such as cirrhosis, hepatocellular carcinoma, insulin resistance, diabetes, and cardiovascular events. Current evidence shows that the immune response has an important participation driving the initiation, maintenance, and progression of the disease. So, various immune imbalances, from cellular to cytokines levels, have been studied, either for better compression of the disease pathophysiology or as biomarkers for severity assessment and outcome prediction. In this article, we performed a thorough review of studies that evaluated the role of inflammatory/immune imbalances in the NAFLD. At the cellular level, we gave special focus on the imbalance between neutrophils and lymphocytes counts (the neutrophil-to-lymphocyte ratio), and that which occurs between T helper 17 (Th17) and regulatory T cells as emerging biomarkers. By extension, we reviewed the reflection of these imbalances at the molecular level through pro-inflammatory cytokines including those involved in Th17 differentiation (IL-6, IL-21, IL-23, and transforming growth factor-beta), and those released by Th17 cells (IL-17A, IL-17F, IL-21, and IL-22). We gave particular attention to the role of IL-17, either produced by Th17 cells or neutrophils, in fibrogenesis and steatohepatitis. Finally, we reviewed the potential of these pathways as new therapeutic targets in NAFLD.

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Section: The Role Of Cellular Immune Imbalances In Nafldmentioning

confidence: 99%

Immune Imbalances in Non-Alcoholic Fatty Liver Disease: From General Biomarkers and Neutrophils to Interleukin-17 Axis Activation and New Therapeutic Targets

Paquissi

2016

Front. Immunol.

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“…A number of inflammation markers have been evaluated to stratify patients for treatment and to predict survival (9). The prognostic value of preoperative systemic inflammationrelated neutrophil-lymphocyte ratio (NLR) and plateletlymphocyte ratio (PLR) has been demonstrated in patients with a variety of cancers (10)(11)(12)(13)(14)(15)(16)(17)(18). However, no previous studies have evaluated the association between NLR and PLR with the prognosis of thymic tumors.…”

Section: Original Articlementioning

confidence: 99%

Prognostic value of preoperative neutrophil-lymphocyte ratio is superior to platelet-lymphocyte ratio for survival in patients who underwent complete resection of thymic carcinoma

Yuan¹,

Gao²,

Mu³

et al. 2016

J. Thorac. Dis.

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Background: Preoperative neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) have prognostic value in patients with various operable tumors. The aim of our study was to determine whether NLR and PLR are predictive of survival in thymic carcinoma patients after complete resection. Results: Univariate analysis found that a high level of NLR was associated with lower disease-free survival (DFS) (HR: 3.385, 95% CI: 1.073-10.678, P=0.037) and lower overall survival (OS) (HR: 12.836, 95% CI:1.615-101.990, P=0.016). The optimal NLR threshold of 4.1 could stratify the patients with high risk of recurrence or metastasis (P=0.026) and death (P=0.006). Meanwhile, the NLR value of >4.1 in those patients was associated with bigger tumor size (P=0.035) and more advanced Masaoka stages (P=0.040) compared with NLR ≤4.1. However, the PLR and other variables were not significantly associated with survival in thymic carcinoma patients. Conclusions:The preoperative NLR of >4.1 was significantly associated with larger tumor size, more advanced Masaoka stages and reduced DFS and OS, but was not an independent predictor of survival in thymic carcinoma patients after complete resection.

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Section: Neutrophil Lymphocyte Ratio (Nlr)mentioning

confidence: 99%

“…An elevated NLR in the peritumoral tissue was also correlated with poor outcomes in patients with HCC (69) Furthermore, peripheral NLR was noted by Motomura et al to be associated with elevated peritumoral interleukin-17 (IL-17) (38). IL-17 itself has been associated with worse OS and increased risk of recurrence as it has been shown to upregulate tumor angiogenesis (70)(71)(72). On the other hand, overall lymphopenia has been associated with poor outcomes after LT as well (73).…”

Section: Neutrophil Lymphocyte Ratio (Nlr)mentioning

confidence: 99%

“…On the other hand, overall lymphopenia has been associated with poor outcomes after LT as well (73). Additionally, elevated AFP, microvascular invasion, and presence of multifocal tumors and extrahepatic metastasis, all factors associated with poor outcomes in HCC patients, are significantly associated with NLR (49,72,74).While NLR is clearly predictive of outcomes in patients undergoing LT or receiving treatment for downstaging HCC, its likely destiny is as an adjunct to other wellvalidated criteria in determining LT candidacy. In multiple studies and most notably in the MORAL score, NLR is a potent predictor post-LT outcome.…”

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confidence: 99%

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Role of inflammatory markers as hepatocellular cancer selection tool in the setting of liver transplantation

Rosenblatt

Tafesh

Halazun

2017

Transl. Gastroenterol. Hepatol.

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Since the advent of the Milan criteria in 1996 and its widespread adoption for selection of patients with hepatocellular carcinoma (HCC) who would benefit from transplant, there has been an extensive hunt for the ideal clinical biomarker to predict HCC recurrence. This is because Milan lack does not include tumor biology indices and recurrence rates remain in the 15-20% range worldwide. While a 'silver-bullet' biomarker has not been found, several useful inflammatory markers have been identified and used in scoring systems that supersede Milan in their ability to predict HCC recurrence post liver transplantation (LT). In this review, we aim to summarize the role of inflammatory markers paly in the selection of HCC patients awaiting LT. measured characteristic to indicate a biological process or response (19). They have the potential to assess the risk of recurrence in HCC without invasive testing, offering yet another tool in a physician's armamentarium to identify the patients who would benefit from LT and those who would not. Currently, several biomarkers are utilized in clinical practice, but both the AASLD and an international consensus (15,20) describe biomarkers as an area of future study. Alpha fetoprotein (AFP) (21)(22)(23)(24) and proteins induced by vitamin K absence II (PIVKA-II) (25-28) have been extensively studied and validated as predictors of HCC outcomes. However, there are patients who do not produce either biomarker and still have high risk of recurrence (29,30). Therefore, pursuing other biomarkers that assess the role of inflammation in malignancy is another method to identify patients at risk of recurrence. The link between inflammation and cancer was postulated in the year 1863 by Virchow, and inflammation has been linked with several gastrointestinal malignancies (31). In the last decade, there has been increasing interest in the use of inflammatory markers as tools to predict poor outcomes in patients with HCC. This review will focus of such inflammatory markers, the role they play in HCC, and how to potentially use these as selection tools for patients awaiting transplant. Neutrophil lymphocyte ratio (NLR)The NLR is a measure of the proportion of peripheral blood neutrophils to lymphocytes and has an important role in predicting outcomes in several malignancies. An elevated NLR can be a marker of both neutrophilia in response to inflammation or peripheral lymphopenia, both first demonstrated the use of NLR in predicting outcomes for HCC in 150 patients undergoing LT for HCC. Of the 13 patients with elevated NLR, 62% had recurrence and, as a cohort, had significantly worse OS and RFS. Of note, even patients within Milan criteria with an elevated NLR, compared to those with normal NLR, had a significantly worse survival (30% vs. 81%) (36). In the largest study in the MELD era from the United States examining post-LT outcomes for HCC, the MORAL score was evaluated for its ability to predict post-LT RFS. The MORAL score was constructed using Cox-regression analyses for factors imp...

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Stratified neutrophil-to-lymphocyte ratio accurately predict mortality risk in hepatocellular carcinoma patients following curative liver resection

Cited by 17 publications

References 42 publications

Immune Imbalances in Non-Alcoholic Fatty Liver Disease: From General Biomarkers and Neutrophils to Interleukin-17 Axis Activation and New Therapeutic Targets

Immune Imbalances in Non-Alcoholic Fatty Liver Disease: From General Biomarkers and Neutrophils to Interleukin-17 Axis Activation and New Therapeutic Targets

Prognostic value of preoperative neutrophil-lymphocyte ratio is superior to platelet-lymphocyte ratio for survival in patients who underwent complete resection of thymic carcinoma

Role of inflammatory markers as hepatocellular cancer selection tool in the setting of liver transplantation

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