O-26 immune profiling provides a set of 5 cytokines to detect hepatocellular carcinoma related to viral hepatitis in south american patients

Introduction and Objectives: New peripheral markers are needed for the early detection of hepatocellular carcinoma (HCC). Currently, the only accepted biomarker is alpha-fetoprotein (AFP) which by itself is suboptimal for early HCC detection. We investigated peripheral immune markers to detect HCC in a large cohort of South American patients and a sub-group of viral hepatitis-related HCC. Materials and Methods: Through the ESCALON network, we prospectively evaluated 127 individuals with HCC and 113 cirrhotic controls from 3 countries in South America (Argentina, Brazil and Ecuador). 42% of HCC cases were related to viral hepatitis B or C. Blood samples were analyzed for 37 unique interleukins, chemokines and growth factors using a multiplex Bio-Rad platform. We used leave-one-out cross-validation (LOOCV) to compute a ROC curve. Results: Median age for HCC patients was 68 y/o and for controls 62 y/o. 70% of cases and 55% of controls were males. 55% of HCCs were under 5cm in diameter. The most common causes of HCC were viral hepatitis (42%) and NAFLD (23%). Twenty-two markers showed a significant difference between cases and controls. Three markers (IL-12p40, Beta-NGF and Gro-alpha) were exclusively dysregulated in viral hepatitis related HCC compared to other HCCs. From all causes of HCCs, we identified five cytokines (MIP-3a, MIG, CCL-25, MDC, and HGF) that were differentially regulated in HCCs compared to cirrhosis controls. ROC analysis of the top-5 markers in HCC cases exclusively related to viral hepatitis showed an AUROC of 0.816 (CI 0.783-0.886). The same panel applied to HCC <5cm related to viral hepatitis showed an AUROC of 0.751 (CI 0.671-0.832). Conclusions: Our study identified a set of 5 cytokines in South American patients that can differentiate HCC from cirrhosis controls in patients with viral hepatitis. The 5 cytokines showed a lower prediction power for HCCs <5cm (likely due to the small size of this cohort).