Development of a Novel Inflammation-Based Index for Hepatocellular Carcinoma

• Published in: Liver cancer (Basel ) Vol. 9; no. 2; pp. 167 - 181
• Main Authors: Chan, Stephen Lam, Wong, Lin-Lee, Chan, Kwan-Chee Allen, Chow, Chit, Tong, Joanna Hung-Man, Yip, Terry Cheuk-Fung, Wong, Grace Lai-Hung, Chong, Charing Ching-Ning, Liu, Po-Hong, Chu, Cheuk-Man, Wong, Vincent Wai-Sun, To, Ka-Fai, Reeves, Helen L., Chan, Anthony Wing-Hung
• Format: Journal Article
• Language: English
• Published: Basel, Switzerland S. Karger AG 01-04-2020
• Subjects: Analysis; Bilirubin; Blood platelets; Cytokines; Gene expression; Hepatoma; Inflammation; Laboratories; Liver; Liver cancer; Lymphocytes; Medical prognosis; Neutrophils; Original Paper; Phosphatases; Hong Kong; United Kingdom; China; United States > US; Japan; Liver cancer; Inflammation; Prognosis; Tumor markers
• ISSN: 2235-1795; 1664-5553
• DOI: 10.1159/000504252

Background: The aim of current study was to (1) construct and validate a novel hepatocellular carcinoma (HCC)-specific inflammatory index; (2) compare the performances of the Integrated Liver Inflammatory Score (ILIS) to existing 4 inflammatory indices in HCC; (3) explore the association between the inflammatory indices and systemic/intratumoral inflammatory markers. Methods: Two cohorts from Hong Kong (HK; n = 1,315) and Newcastle (n = 574) were studied. A novel index was constructed from the HK training set (n = 627). The index was constructed from the training set by combing independent prognostic circulating parameters, followed by validating in the validation set of HK cohort (n = 688) and the Newcastle cohort. Its prognostic performance was compared to 4 inflammatory indices, namely, the neutrophil to lymphocyte ratio, platelet-to-lymphocyte ratio, prognostic nutrition index, and systemic immune-inflammation index, were compared in the HK cohort. Circulating cytokines and intratumoral gene expression were analyzed in a subset of patients with available samples and correlated with the inflammatory indices. Results: In the training set of the HK cohort, the ILIS, was generated: –0.057 × albumin (g/L) + 0.978 × log (Bilirubin, µmol/L) + 1.341 × log (alkaline phosphatase, IU/L) + 0.086 × Neutrophil (10 9 /L) + 0.301 × log (alpha-fetoprotein, µg/L). With cutoff of 2.60 and 3.87, the ILIS could categorize patients into 3 risk groups in the both validation cohorts. ILIS outperforms other inflammatory indices and remains an independent prognosticator for overall survival after adjustment with Barcelona Clinic Liver Cancer (hazard ratio 31.90, p < 0.001). The ILIS had the best prognostic performances as compared to other inflammatory indices. In exploratory analyses, the ILIS correlated with circulating inflammatory cytokines (e.g., IL-8) but not with any intratumoral inflammatory gene expression. Conclusions: ILIS is an HCC-specific prognostic index built on 5 readily available blood parameters. Its versatility is validated both Eastern and Western population of HCC. The score is correlated with levels of circulating cytokines.