The Relationship Between Serum Interleukin-6 and the Recurrence of Hepatitis B Virus Related Hepatocellular Carcinoma after Curative Resection

Abstract

The aim of this study is to assess whether preoperative serum interleukin-6 (IL-6) can predict recurrence of hepatitis B virus (HBV)-associated hepatocellular carcinoma (HCC).The association between preoperative IL-6 levels and HCC recurrence following curative hepatectomy in 146 patients with chronic HBV infection was determined. Patients were divided into groups based on the presence or absence of HCC recurrence. Serum IL-6 levels were compared between groups, and the association between serum IL-6 level and greatest tumor dimension was also analyzed. Receiver operating characteristics (ROC) curve was used to define the optimal cutoff value for predicting recurrence-free survival (RFS) and overall survival (OS) rates. The OS and RFS rates were calculated using the Kaplan-Meier method.Out of 146 patients, 80 (54.8%) patients were documented as having HCC recurrence during the follow-up period. After adjusting for potential confounders, serum IL-6 levels were significantly associated with HCC recurrence, and a saturation effect existed with serum IL-6 levels up to 3.7 pg/mL. In addition, patients with preoperative serum IL-6 levels over 3.1 pg/mL had lower RFS and OS rates (P < 0.01). There was no significant correlation between preoperative serum IL-6 levels and maximal tumor dimension (r = 0.0003, P = 0.84).Elevated serum levels of IL-6 were significantly associated with an increased risk of HBV-associated HCC recurrence suggesting that preoperative IL-6 serum level is potential biomarker for early prediction of HBV-associated HCC recurrence.

The association between preoperative serum interleukin‐6 levels and postoperative prognosis in patients with T2 gallbladder cancer

“…It is continuously produced and secreted by various types of cells including T cells, endothelial cells, macrophages, and tumor cells themselves . Many clinical studies independently reported a significant correlation between the concentration of IL‐6 and patient prognosis in various cancer types . In concordance with these studies, our study also documented that a high concentration of preoperative serum IL‐6 is associated with negative prognosis among patients with hepatic side T2 GBC.…”

“…It has been reported that IL‐6‐mediated activation of the JAK‐STAT3 signaling pathway is a principal pathway implicated in tumor formation and metastatic progression . Clinically, the predictive ability of serum IL‐6 was observed in several types of tumors, including breast cancer, lung cancer, renal cell carcinoma, hepatocellular carcinoma, bladder cancer, prostate cancer, and pancreatic cancer . More importantly, some preclinical and translational findings suggested that IL‐6 signaling blockade may have therapeutic indications in some of the cancers mentioned above, including ovarian clear cell adenocarcinoma, progressive metastatic renal cell carcinoma, and metastatic castration‐resistant prostate cancer .…”

Involvement of soluble B7‑H3 in combination with the serum inflammatory cytokines interleukin‑17, ‑8 and ‑6 in the diagnosis of hepatocellular carcinoma

“…In order to clarify the clinical effects and associations of IL-6, IL-27, TNF-α and vascular endothelial growth factor with signal transducer and activator of transcription proteins under different clinical and pathological stages of HCC, Kao et al (33) demonstrated that overexpression of IL-6 was closely associated with maintaining liver function and 6-month mortality rate in HCC while the elevated IL-27, TNF-α, or VEGF presented no significant correlation with 6-month mortality rate in HCC. In addition, determinations of preoperative IL-6 serum levels can serve as a potential biomarker for the early prediction of hepatitis B virus-related HCC relapse (34). Results from the present study revealed that serum levels of soluble IL-17 in HCC patients were significantly increased and positively associated with sB7-H3 levels, but that they were negatively associated with IL-8 levels.…”

HBV Facilitated Hepatocellular Carcinoma Cells Proliferation by Up-Regulating Angiogenin Expression Through IL-6

“…As a potent pleiotropic inflammatory cytokine, IL-6 has been shown to play an important role in the pathogenesis of liver cancer, including stimulating cell proliferation and hepatic remodeling. Additionally, it also plays an important role in the survival of patients received hepatectomy [40-42]. IL-6 is usually elevated in those infected HBV, and is closely related to the pathogenesis of HCC [43].…”