Host immune status and incidence of hepatocellular carcinoma among subjects infected with hepatitis C virus: a nested case-control study in Japan.
A nested case-control study was conducted to examine the association between host immune status, as characterized by serum immune marker levels, and the development of hepatocellular carcinoma (HCC) up to 8 years later in persons with chronic hepatitis C virus (HCV) infection. Cases (n = 39) and matched controls (n = 117) were selected from participants of the Town C HCV Study in Japan between 1996 and 2004 and matched on age at first available sample (+/-1 year), gender, and length of follow-up. Separate analyses were done for each of three serum immune markers: soluble tumor necrosis factor-receptor II (sTNF-R2) and soluble intercellular adhesion molecule-1 (sICAM-1), as indicators of type 1, cell-mediated immune response, and soluble CD30 (sCD30), as an indicator of type 2, humoral immune response. The median concentrations of sTNF-R2, sICAM-1, and sCD30 among controls were 3,170 pg/mL, 305 ng/mL, and 3.0 units/mL, respectively, and were higher among cases (3,870 pg/mL, 372 ng/mL, and 3.3 units/mL, respectively). The risk of developing HCC among subjects with immune marker concentrations above the median levels of the controls was >2-fold greater than among subjects with lower concentrations for all three markers [sTNF-R2: odds ratio (OR), 6.9; 95% confidence interval (95% CI), 2.4-20.5; sICAM-1: OR, 2.0; 95% CI, 0.9-4.1; and sCD30: OR, 2.1; 95% CI, 1.0-4.7]. Simultaneous adjustment for all three markers revealed only sTNF-R2 to be associated with HCC risk (OR, 6.4; 95% CI, 2.0-20.6). Adjustment for alcohol consumption and HCV serotype did not materially alter these associations. Results from this prospective, community-based study suggest that a dysregulation in both type 1-related and type 2-related host immunity contributes to the development of HCV-associated HCC.
Suruki
Robert Y
RY
Department of Epidemiology, Harvard School of Public Health, USA. suruki@post.harvard.edu
Mueller
Nancy
N
Hayashi
Katsuhiro
K
Harn
Donald
D
DeGruttola
Victor
V
Raker
Christina A
CA
Tsubouchi
Hirohito
H
Stuver
Sherri O
SO
D000368:Aged; D015415:Biomarkers; D006528:Carcinoma, Hepatocellular / Q000453:epidemiology / Q000276:immunology* / Q000821:virology; D016022:Case-Control Studies; D005260:Female; D016174:Hepacivirus / Q000302:isolation & purification*; D019698:Hepatitis C, Chronic / Q000276:immunology*; D006801:Humans; D007564:Japan / Q000453:epidemiology; D008113:Liver Neoplasms / Q000453:epidemiology / Q000276:immunology* / Q000821:virology; D008297:Male; D012307:Risk Factors
D015415:Biomarkers