Serum IL-6 levels and the risk for hepatocarcinogenesis in chronic hepatitis C patients: an analysis based on gender differences.

Nakagawa H, Maeda S, Yoshida H, Tateishi R, Masuzaki R, Ohki T, Hayakawa Y, Kinoshita H, Yamakado M, Kato N, Shiina S, Omata M
Int J Cancer. 2009 125 (10): 2264-9

PMID: 19585572 · DOI:10.1002/ijc.24720

Interleukin-6 (IL-6) may play a role in the pathogenesis of hepatocellular carcinoma (HCC). Recently, it was reported in mouse models that estrogen-mediated inhibition of IL-6 production explains the gender disparity in HCC. We conducted a retrospective cohort study to examine whether this hypothesis is applicable to human HCC. We enrolled 330 patients with chronic hepatitis C whose serum samples were collected between January 1994 and December 2002. Serum IL-6 concentrations were measured and patients were divided into three groups according to IL-6 levels: low, middle, and high. We evaluated the association between serum IL-6 levels and the risk of subsequent HCC development, including subgroup analysis on each gender. During the follow-up period (mean 9.0 yr), HCC developed in 126 patients. The incidence rates differed significantly among the three groups (p = 0.015), increasing in accordance with serum IL-6 levels. However, unexpectedly, this tendency was significant only in female patients. In a multivariate analysis, higher serum IL-6 level was an independent risk factor for HCC development in female patients, with a hazard ratio of 1.61. Although female patients showed a weak negative correlation between serum IL-6 levels and estradiol levels, the lower risk of HCC in female patients cannot be fully explained by estrogen-mediated inhibition of IL-6 production. In conclusion, higher serum IL-6 level was an independent risk factor for HCC development in female but not male chronic hepatitis C patients. Measurement of serum IL-6 levels may provide useful information for predicting future HCC development in female chronic hepatitis C patients.

MeSH Terms (16)

Biomarkers, Tumor Carcinoma, Hepatocellular Cohort Studies Estrogens Female Hepacivirus Hepatitis C, Chronic Humans Interleukin-6 Liver Neoplasms Male Middle Aged Prognosis Retrospective Studies Risk Factors Sex Factors

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