title: Hepatic radiofrequency ablation causes an increase of circulating histones in patients with hepatocellular carcinoma.
abstract: 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.
authors: a Department of Oncology , First Hospital of Qinhuangdao , Qinhuangdao, Hebei Province, P.R. China.
authors: Tao
authors: T
authors: Gu
authors: Yang
authors: Y
authors: Ge
authors: Yuezhang
authors: Y
authors: Song
authors: Zhanzhao
authors: Z
authors: Fu
authors: Yunjie
authors: Y
authors: Zhang
authors: Guangxia
authors: G
authors: Wang
authors: Shasha
authors: S
authors: Shao
authors: Tao
authors: T
authors: Wen
mesh_terms: D055011:Ablation Techniques / Q000009:adverse effects*; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D006528:Carcinoma, Hepatocellular / Q000097:blood / Q000601:surgery*; D016207:Cytokines / Q000097:blood; D005260:Female; D006657:Histones / Q000097:blood*; D006801:Humans; D007249:Inflammation / Q000209:etiology / Q000473:pathology; D008297:Male; D008875:Middle Aged; D018375:Neutrophil Activation
chemical_list: D015415:Biomarkers; D016207:Cytokines; D006657:Histones
keywords: Radiofrequency ablation; cytokines; hepatocellular carcinoma; histones; myeloperoxidase