Development of a Novel Inflammation-Based Index for Hepatocellular Carcinoma
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AbstractBackground: 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 x albumin (g/L) + 0.978 x log (Bilirubin, mu mol/L) + 1.341 x log (alkaline phosphatase, IU/L) + 0.086 x Neutrophil (10(9)/L) + 0.301 x log (alpha-fetoprotein, mu g/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.
All Author(s) ListChan SL, Wong LL, Chan KA, Chow C, Tong JH, Yip TC, Wong GL, Chong CC, Liu PH, Chu CM, Wong VW, To KF, Reeves HL, Chan AW
Journal nameLiver Cancer
Year2020
Month4
Volume Number9
Issue Number2
PublisherKarger Publishers Open Access
Pages167 - 181
ISSN2235-1795
eISSN1664-5553
LanguagesEnglish-United Kingdom

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