Hepatic radiofrequency ablation causes an increase of circulating histones in patients with hepatocellular carcinoma.

Background: Radiofrequency ablation (RFA) has been increasingly accepted for the treatment of hepatocellular carcinoma (HCC). However, RFA has been associated with an obvious systemic inflammatory response, but little is known about the underlying mechanisms. Circulating histones are recently identified as pivotal inflammatory mediators. Hence, we investigated whether circulating histones are involved in RFA-related inflammation.

Methods: Serial blood samples were collected from 42 HCC patients undergoing RFA at 3 time points: pre-RFA, post-RFA (within 24 h), and in 4-week follow up after RFA. Plasma histones, myeloperoxidase (MPO), inflammatory cytokines (IL-1β, IL-6, IL-10, TNF-α), liver damage parameters (ALT, AST), and creatinine were measured.

Results: Compared to pre-RFA (0.837 μg/ml), there was a significant increase in the levels of circulating histones within 24 h post-RFA (4.576 μg/ml, p < 0.0001); histones decreased to pre-RFA levels in 4-week follow up after RFA. Meanwhile, MPO, IL-6, and IL-10 were elevated remarkably within 24 h post-RFA, indicative of an occurrence of the inflammatory response. Notably, histone levels correlated well with MPO (r = 0.5678), IL-6 (r = 0.4851), and IL-10 (r = 0.3574), respectively. In addition, there was a significant damage of liver function in patients within 24 h post-RFA, evidenced by the increased levels of ALT and AST. No changes in creatinine levels were observed.

Conclusions: These data demonstrate that circulating histones are excessively released in HCC patients treated with RFA, which may lead to systemic inflammation by stimulating neutrophil activation and promoting cytokine production. Circulating histones may act as a novel marker to indicate the extent of inflammation related to RFA.