Serum IL-6 levels and the risk for hepatocarcinogenesis in chronic hepatitis C patients: an analysis based on gender differences.
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.
Nakagawa
Hayato
H
Department of Gastroenterology, University of Tokyo, Tokyo 113-8655, Japan. n-hayato@yf7.so-net.ne.jp
Maeda
Shin
S
Yoshida
Haruhiko
H
Tateishi
Ryosuke
R
Masuzaki
Ryota
R
Ohki
Takamasa
T
Hayakawa
Yoku
Y
Kinoshita
Hiroto
H
Yamakado
Minoru
M
Kato
Naoya
N
Shiina
Shuichiro
S
Omata
Masao
M
D014408:Biomarkers, Tumor / Q000097:blood*; D006528:Carcinoma, Hepatocellular / Q000097:blood* / Q000821:virology; D015331:Cohort Studies; D004967:Estrogens / Q000097:blood; D005260:Female; D016174:Hepacivirus / Q000302:isolation & purification*; D019698:Hepatitis C, Chronic / Q000097:blood* / Q000821:virology; D006801:Humans; D015850:Interleukin-6 / Q000097:blood*; D008113:Liver Neoplasms / Q000097:blood* / Q000821:virology; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012189:Retrospective Studies; D012307:Risk Factors; D012737:Sex Factors
D014408:Biomarkers, Tumor; D004967:Estrogens; D015850:Interleukin-6