Neutrophil-to-lymphocyte ratio for the prognostic assessment of hepatocellular carcinoma: A systematic review and meta-analysis of observational studies

Qi, Xingshun; Li, Jianjun; Deng, Han; Li, Hongyu; Su, Chunping; Guo, Xiaozhong

doi:10.18632/oncotarget.9942

Cited by 90 publications

(70 citation statements)

References 90 publications

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“…The range of reported cut-off values of the NLR was from about 1.0 to 5.0, which is too wide. According to the meta-analysis by Qi et al, the statistically significant cut-off value was 5.0 or within the range from about 2.0 to 3.0 [26]. Our cut-off value of 2.1 is within this range and was also statistically significant.…”

Section: Discussionsupporting

confidence: 54%

“…Lymphocytes are related to a T lymphocyte-mediated antitumor response [24], and a decreased lymphocyte number reflects a weaker lymphocyte-mediated immune response to the tumor [25]. Therefore, the NLR reflects the potential balance between neutrophil-associated pro-tumor inflammation and lymphocyte-dependent anti-tumor immune function; a high NLR is likely to reflect a more aggressive disease and poor prognosis [17, 26, 27]. …”

Section: Discussionmentioning

confidence: 99%

“…In patients with HCC, a prognostic role of the NLR has been investigated after treatments including surgical resection [10, 17], transplantation [14], RFA [16], TACE [18–20], and sorafenib [15]. In addition, a recently reported meta-analysis demonstrated the role of the NLR [26]. This analysis revealed that low baseline NLR was significantly associated with better OS (hazard ratio [HR], 1.80; 95% confidence interval [CI], 1.59–2.04, p < 0.001) and recurrence-free or disease-free survival (HR, 1.80; 95% CI, 1.80–2.76, p < 0.001).…”

Section: Discussionmentioning

confidence: 99%

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Pre-radiotherapy neutrophil-to-lymphocyte ratio as an independent prognostic factor in patients with locally advanced hepatocellular carcinoma treated with radiotherapy

Son

Park

et al. 2016

Oncotarget

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We aimed to investigate the pre-radiotherapy neutrophil-to-lymphocyte ratio (prNLR) as a prognostic factor in patients with locally advanced hepatocellular carcinoma (HCC) treated with radiotherapy (RT), and to determine the optimal cut-off value for prNLR. We retrospectively evaluated 56 patients with locally advanced HCC treated with RT (helical tomotherapy) between March 2006 and February 2012. The optimal cut-off value was determined by using a maximally selected log-rank test. Prognostic factors that influence the local progression-free survival (PFS) and overall survival (OS) were evaluated. A prNLR of 2.1 was determined to be the optimal cut-off value. In a comparison between the high-prNLR group and the low-prNLR group, there was a 13.1-month difference in the median OS (10.3 vs. 23.4 months, p = 0.003) and a 10.4-month difference in the median local PFS (7.1 vs. 17.5 months, p = 0.001). On multivariate analysis of prognostic factors for local PFS and OS, the prNLR was identified as an independent prognostic factor, and the hazard ratio was 4.2 and 2.5, respectively. We demonstrated that a low prNLR was significantly associated with better PFS and OS in patients with locally advanced HCC treated with RT, and the prNLR should be considered as an independent prognostic factor in these patients.

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Section: Discussionsupporting

confidence: 54%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Pre-radiotherapy neutrophil-to-lymphocyte ratio as an independent prognostic factor in patients with locally advanced hepatocellular carcinoma treated with radiotherapy

Son

Park

et al. 2016

Oncotarget

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“…In addition, heterogeneous tumor stages and treatment modalities were considered [11]. Finally, arguments supporting the usefulness of the NLR in advanced HCC patients receiving medical treatments encompass few retrospective series, of which three have been published in full-text form [12–14].…”

Section: Introductionmentioning

confidence: 99%

Prognostic value of the neutrophil-to-lymphocyte ratio in the ARQ 197-215 second-line study for advanced hepatocellular carcinoma

et al. 2017

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The ARQ 197-215 study randomized patients to tivantinib or placebo and pre-specified efficacy analyses indicated the predictive value of MET expression as a marker of benefit from tivantinib in hepatocellular carcinoma (HCC). We aimed to explore the neutrophil-to-lymphocyte ratio (NLR) in 98 ARQ 197-215 patients with available absolute neutrophil count and absolute lymphocyte count at baseline. The cut-off value used to define high versus low NLR was 3.0. In univariate analysis, high NLR was associated with hazard ratio (HR) for overall survival (OS) of 1.58 [95% confidence interval (CI) 1.01; 2.47; P <0.046], corresponding to median OS of 5.1 months versus 7.8 months in patients with low NLR (P = 0.044). In contrast, time to progression was not significantly affected by NLR (P = 0.20). Multivariable model confirmed that both NLR >3 (P = 0.03) and presence of vascular invasion (P = 0.017) were negatively associated with OS. After adjustment for vascular invasion, NLR independently predicted survival in both the placebo and the tivantinib cohort. For OS, no interaction was detected between NLR status and treatment (Pinteraction = 0.40). Baseline NLR is an independent prognostic biomarker in patients with HCC and compensated liver function who are candidate for second-line treatments.

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“…Another large study of patients with LT for HCC noted that as NLR increased each log unit, the risk of HCC recurrence nearly doubled (41). Not only has NLR been demonstrated to be predictive of survival in patients undergoing LT for HCC, it has been successful in evaluating patients undergoing tumor downstaging procedures such as radiofrequency ablation (RFA) (44)(45)(46) and transcatheter arterial chemoembolization (TACE) (47). In a study of 163 patients, most of which had viral hepatitis, with HCC treated with RFA, NLR post-RFA was strongly predictive of survival.…”

Section: Neutrophil Lymphocyte Ratio (Nlr)mentioning

confidence: 99%

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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Neutrophil-to-lymphocyte ratio for the prognostic assessment of hepatocellular carcinoma: A systematic review and meta-analysis of observational studies

Cited by 90 publications

References 90 publications

Pre-radiotherapy neutrophil-to-lymphocyte ratio as an independent prognostic factor in patients with locally advanced hepatocellular carcinoma treated with radiotherapy

Pre-radiotherapy neutrophil-to-lymphocyte ratio as an independent prognostic factor in patients with locally advanced hepatocellular carcinoma treated with radiotherapy

Prognostic value of the neutrophil-to-lymphocyte ratio in the ARQ 197-215 second-line study for advanced hepatocellular carcinoma

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

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