Utility of Serum Inflammatory Markers for Predicting Microvascular Invasion and Survival for Patients with Hepatocellular Carcinoma

Zheng, Jianbao; Seier, Ken; Gönen, Mithat; Balachandran, Vinod P.; Kingham, T. Peter; D’Angelica, Michael I.; Allen, Peter J.; Jarnagin, William R.; DeMatteo, Ronald P.

doi:10.1245/s10434-017-6060-7

Cited by 69 publications

(52 citation statements)

References 41 publications

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“…NLR, PLR and LMR are considered systemic inflammatory biomarkers and have been investigated in patients with various types of cancer. High PLR was associated with worse OS and RFS in (mostly non‐cirrhotic) patients with HCC. These findings were not validated by another study, in which both NLR and LMR, but not PLR, were independently predictive of RFS in HCC associated with HBV‐related cirrhosis.…”

Section: Discussionmentioning

confidence: 96%

Prognostic significance of inflammatory biomarkers in hepatocellular carcinoma following hepatic resection

et al. 2019

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Background Cancer‐related inflammation has been correlated with cancer prognosis. This study evaluated inflammatory biomarkers, including neutrophil‐to‐lymphocyte ratio (NLR), platelet‐to‐lymphocyte ratio (PLR) and lymphocyte‐to‐monocyte ratio (LMR), programmed death ligand (PD‐L) 1 expression, and tumour microenvironment in relation to prognosis and clinicopathological features of patients with hepatocellular carcinoma (HCC) undergoing curative hepatic resection. Methods Patients who had liver resection for HCC in 2000–2011 were analysed. Univariable and multivariable analyses were conducted for overall (OS) and recurrence‐free (RFS) survival. Immunohistochemical analyses of PD‐L1, CD8 and CD68 expression were performed. HCC cell lines were evaluated for PD‐L1 expression. A subgroup analysis was conducted to determine patient features, survival and the tumour microenvironment. Results were validated in a cohort of patients with HCC treated surgically in 2012–2016. Results Some 281 patients who underwent hepatic resection for HCC were included. Multivariable analysis showed that low LMR was an independent prognostic factor of OS (hazard ratio (HR) 1·59, 95 per cent c.i. 1·00 to 2·41; P = 0·045) and RFS (HR 1·47, 1·05 to 2·04; P = 0·022) after resection. Low preoperative LMR values were correlated with higher α‐fetoprotein values (P < 0·001), larger tumour size (P < 0·001), and high rates of poor differentiation (P = 0·035) and liver cirrhosis (P = 0·008). LMR was significantly lower in PD‐L1‐positive patients than in those with PD‐L1 negativity (P < 0·001). Results were confirmed in the validation cohort. PD‐L1 expression was upregulated in HCC cell lines treated with interferon‐γ and co‐cultured with THP‐1 monocyte cells. Conclusion LMR is an independent predictor of survival after hepatic resection in patients with HCC. Modulation of the immune checkpoint pathway in the tumour microenvironment is associated with a low LMR.

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Section: Discussionmentioning

confidence: 96%

Prognostic significance of inflammatory biomarkers in hepatocellular carcinoma following hepatic resection

et al. 2019

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“…Most reports that evaluated prognostic factors for HCC patients have not included serosal invasion . Furthermore, although some reports have evaluated tumor rupture and invasion into adjacent organs, microscopic serosal invasion has rarely been assessed .…”

Section: Discussionmentioning

confidence: 99%

“…One of the reasons for this poor prognosis is the high incidence of recurrence after hepatectomy . Patient characteristics, underlying liver disease, and tumor‐related factors are reportedly prognostic factors for HCC after hepatectomy . Regarding tumor‐related factors, the number of tumors, maximum size of tumors, presence of vascular invasion, and histological type of tumors have all been reported as prognostic factors for patients with HCC .…”

Section: Introductionmentioning

confidence: 99%

Serosal invasion is a strong prognostic factor for hepatocellular carcinoma after hepatectomy

Sakamoto

Ogawa

Tohyama

et al. 2018

Hepatology Research

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Aim: The clinical impact of serosal invasion by hepatocellular carcinoma (HCC) remains unclear. This study aimed to clarify the significance of serosal invasion as a prognostic factor for patients who underwent hepatectomy for HCC.Methods: This retrospective study investigated patients who underwent hepatectomy for HCC between October 2003 and September 2016 in Ehime University Hospital (Toon, Japan). A total of 161 cases were enrolled after excluding cases of concomitant distant metastasis, macroscopic tumor remnant, mixed HCC, and rehepatectomy. We classified these 161 patients into groups with serosal invasion detected (S[+]) and serosal invasion undetected (S[À]). We compared patient characteristics, perioperative data, pathological findings, and prognosis between S(+) and S(À) groups.Results: Serosal invasion was observed in 19 of the 161 patients (12%). The 5-year recurrence-free survival rate was lower for S(+) (13.0%) than for S(À) (28.7%, P = 0.006). The 5-year overall survival (OS) rate was lower for S(+) (24.7%) than for S(À) (63.9%, P < 0.001). Regarding OS, serosal invasion, preoperative α-fetoprotein value, presence of invasion to hepatic veins, and liver cirrhosis were independent predictors in multivariate analyses. The 3-year OS rate after recurrence was poorer in the S(+) group (22.9%) than in the S(À) group (49.7%, P = 0.001).Conclusions: Serosal invasion was a strong predictor of worse outcomes after hepatectomy for HCC. Patients showing serosal invasion need close postoperative follow-up or consideration of adjuvant treatment.

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“…Few studies have investigated the relationship between PLR and mVI (Ma et al, 2016;Zheng et al, 2017). Ma (2016) performed a meta-analysis of the prognostic value of PLR in HCC and found no association with vascular invasion; however, this conclusion was based on only three eligible studies, and vascular invasion was defined as including both macrovascular invasion and mVI.…”

Section: Discussionmentioning

confidence: 99%

“…In addition, several recent studies have identified several serum inflammatory factors associated with post-treatment prognosis of HCC, including platelet-to-lymphocyte ratio (PLR) (Tian et al, 2016;Huang et al, 2017;Yang et al, 2017), neutrophil-to-lymphocyte ratio (NLR) (Goh et al, 2016;Jin et al, 2017;Urabe et al, 2017), and prognostic nutritional index (PNI) (Chan et al, 2015;Wu et al, 2016). However, only a few studies have examined the relationship between inflammatory indices and mVI (Gomez et al, 2008;Chan et al, 2015;Zheng et al, 2017). The aim of this study was to identify preoperative predictors of mVI by evaluating the correlation between preoperative clinicopathological features, including serum inflammatory indices, and mVI.…”

Section: Introductionmentioning

confidence: 99%

Platelet-to-Lymphocyte Ratio and Large Tumor Size Predict Microvascular Invasion after Resection for Hepatocellular Carcinoma

Rungsakulkij

Mingphruedhi

Suragul

et al. 2018

Asian Pac J Cancer Prev

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Background: Recurrence after curative resection of hepatocellular carcinoma (HCC) is associated with early death and poor prognosis. Microvascular invasion (mVI) is strongly associated with disease recurrence. Although many studies have examined the relationship between various serum inflammatory indices and post-treatment prognosis, little is known about preoperative predictors of microvascular invasion in HCC. Methods: Patients who underwent curative hepatic resection for HCC at our institute from January 2006 to December 2016 were retrospectively reviewed. The associations between mVI and various potential risk factors, including tumor size, hepatitis B and C virus infection, Child-Pugh scores, platelet-to-lymphocyte ratio, and neutrophil-to-lymphocyte ratio, were analyzed. Optimal cutoff values were determined using receiver operating characteristic curves. Results: A total of 330 HCC patients were enrolled in this study, of whom 74 (22.4%) had tumors with mVI. After univariate analysis, two parameters were significantly associated with mVI after hepatic resection: platelet-to-lymphocyte ratio ≥102 (odds ratio [OR] 2.385, p = 0.001) and tumor size ≥5 cm (OR 4.29, p < 0.001). Both variables remained significant risk factors for mVI after multivariate analysis: platelet-to-lymphocyte ratio ≥102 (OR 1.831, p = 0.034) and tumor size ≥5 cm (OR 3.791, p < 0.001). Conclusions: Large tumor size (≥5 cm) and high platelet-to-lymphocyte ratio (≥102) are independent predictive factors for mVI in HCC.

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Utility of Serum Inflammatory Markers for Predicting Microvascular Invasion and Survival for Patients with Hepatocellular Carcinoma

Abstract: This largest Western series to evaluate the utility of preoperative inflammatory markers in patients with HCC found that only PLR was associated with RFS and OS and that albumin was associated with MVI.

Cited by 69 publications

References 41 publications

Prognostic significance of inflammatory biomarkers in hepatocellular carcinoma following hepatic resection

Prognostic significance of inflammatory biomarkers in hepatocellular carcinoma following hepatic resection

Serosal invasion is a strong prognostic factor for hepatocellular carcinoma after hepatectomy

Platelet-to-Lymphocyte Ratio and Large Tumor Size Predict Microvascular Invasion after Resection for Hepatocellular Carcinoma

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