The Severity of Liver Fibrosis Influences the Prognostic Value of Inflammation-Based Scores in Hepatitis B-Associated Hepatocellular Carcinoma
This study was designed to evaluate the prognostic value of three systemic inflammation markers, neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), and prognostic nutritional index (PNI), for hepatocellular carcinoma (HCC) associated with hepatitis B (HBV).
This analysis included 234 HBV-HCC patients who underwent primary surgical resection at the Mount Sinai Medical Center between 1988 and 2013. Serum albumin and circulating neutrophil, lymphocyte, and platelet counts immediately before surgery were obtained to calculate NLR, PLR, and PNI.
Patients with larger tumor size (>3 cm) had higher NLR, higher PLR, and lower PNI. Stratified analysis showed that the impact of three markers on outcome depends on the severity of liver fibrosis. High NLR, high PLR, or low PNI was associated with poor outcome only in patients without end-stage fibrosis (Ishak stage 0–5) and not in those with cirrhosis (Ishak stage 6). Multivariate analysis in Ishak stage 0–5 patients showed that only high NLR was associated with poor outcome independent of tumor size. Of the three markers, only NLR correlated with PD-L1 expression in center of tumor, but not in nonneoplastic liver.
The prognostic value of these three markers following surgery was only significant for HBV-HCC patients without end-stage fibrosis, and among the three markers, only NLR remained a significant prognostic indicator independent of tumor size. The correlation of NLR with intratumoral PD-L1 expression raises a hypothesis for shared pathways leading to PD-L1-mediated local tolerance within tumor and systemic inflammatory responses represented by elevated NLR in HBV-HCC.
- 3.Wang Q, Fiel MI, Blank S, Luan W, Kadri H, Kim KW, et al. Impact of liver fibrosis on prognosis following liver resection for hepatitis B-associated hepatocellular carcinoma. Br J Cancer. 2013;11(10):352.Google Scholar
- 11.Li M-x, Liu X-m, Zhang X-f, Zhang J-f, Wang W-l, Zhu Y, et al. Prognostic role of neutrophil-to-lymphocyte ratio in colorectal cancer: a systematic review and meta-analysis. Int J Cancer. 2013;134(10):2403–13.Google Scholar
- 13.Dirican A, Kucukzeybek BB, Alacacioglu A, Kucukzeybek Y, Erten C, Varol U, et al. Do the derived neutrophil to lymphocyte ratio and the neutrophil to lymphocyte ratio predict prognosis in breast cancer? Int J Clin Oncol 2014;18:18.Google Scholar
- 14.Oh BS, Jang JW, Kwon JH, You CR, Chung KW, Kay CS, et al. Prognostic value of C-reactive protein and neutrophil-to-lymphocyte ratio in patients with hepatocellular carcinoma. BMC Cancer. 2013;13(78):1471–2407.Google Scholar
- 20.Wang Q, Fiel MI, Luan W, Blank S, Kadri H, Kim KW, et al. Impact of intrahepatic hepatitis B DNA and covalently closed circular DNA on survival after hepatectomy in HBV-associated hepatocellular carcinoma patients. Ann Surg Oncol. 2013;15:15.Google Scholar
- 22.Kadri HS, Blank S, Wang Q, Kim KW, Fiel MI, Luan W, et al. Outcomes following liver resection and clinical pathologic characteristics of hepatocellular carcinoma occurring in patients with chronic hepatitis B and minimally fibrotic liver. Eur J Surg Oncol. 2013;39(12):1371–6.PubMedCrossRefGoogle Scholar