Circulating cytokines reflect the etiology-specific immune environment in cirrhosis and HCC

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Background and AimsChronic liver disease -from any etiology- can progress to fibrosis, cirrhosis and hepatocellular carcinoma (HCC). The progression of liver cirrhosis to the end stages of disease is influenced by a variety of factors, including inflammatory cytokines (soluble inflammatory mediators of cell communication). We pursued a study of cytokine-mediated inflammatory responses in hepatitis B (HBV), hepatitis C (HCV), alcoholic liver disease (ALD) and non-alcoholic fatty liver disease (NAFLD) patients with liver cirrhosis. MethodsImmune profiles were determined through serum multiplex profiling of >100 cytokines in a 188 cirrhotic patients, 35 healthy controls and 198 early-stage HCC patients.ResultsPatients with liver cirrhosis exhibited vast upregulation of proinflammatory cytokines (p<0.0001), including those with pro-oncogenic features, when compared to healthy individuals. In contrast to prevailing assumptions, each etiological cause of cirrhosis exhibited a unique cytokine profile in blood. Regardless of antiviral therapy, HBV cirrhosis patients had the largest number of upregulated proinflammatory mediators, compared to HCV, ALD and NAFLD (p<0.0001). To further evaluate the etiology-dependent modulation of cytokine response in relation to liver cancer, we studied cytokine profiles in early-stage HCC patients strictly stratified by underlying liver disease. We observed unique sets of differentially expressed cytokines in each cohort of early-stage HCC patients of different cirrhosis etiologies. ConclusionsOur findings, therefore, underscore the importance of stratification by etiological cause of liver cirrhosis in immune-based studies.