Cytokines are associated with postembolization fever and survival in hepatocellular carcinoma patients receiving transcatheter arterial chemoembolization

Cytokines play important roles in angiogenesis, inflammation, and cell growth. The present study aimed to investigate the correlation between cytokine changes and clinical characteristics in hepatocellular carcinoma (HCC) patients receiving transcatheter arterial chemoembolization (TACE). Forty-one TACE-naive HCC patients receiving 73 sessions of TACE and 30 healthy controls were studied. Serum levels of tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), interleukin-8 (IL-8), vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), angiogenin, epidermal growth factor (EGF), epidermal growth factor receptor, and transforming growth factor beta 1 (TGF-beta 1) before and at 1, 3, 5, 7, and 14 days after TACE as well as clinical parameters were analyzed. Baseline serum levels of VEGF, bFGF, IL-6, IL-8, and TNF-alpha in HCC patients were significantly elevated, whereas EGF and TGF-beta 1 levels were lower compared to those in healthy controls (p < 0.05 for all). Serum IL-6 increased rapidly and peaked on day 1 after TACE administration, whereas VEGF increased more slowly and peaked on day 14 after TACE administration. Patients with post-TACE fever had higher serum IL-6 levels on days 1, 3, and 5 (p < 0.005 for all). Patients with pre-TACE serum VEGF < 200 pg/ml had a longer survival than those with pre-TACE serum VEGF levels a parts per thousand yen 200 pg/ml (22.2 months vs. 11.6 months, p = 0.014). Cox multivariate analysis showed that baseline serum VEGF significantly predicted survival for HCC patients receiving TACE. TACE is associated with the modulation of serum angiogenic, inflammatory, and cell growth cytokines in HCC patients. Serum IL-6 correlates with post-TACE fever, and baseline serum VEGF independently predicts patient survival.