High serum interleukin‐6 level predicts future hepatocellular carcinoma development in patients with chronic hepatitis B

Increased interleukin‐6 (IL‐6) production is implicated in the pathogenesis of hepatocellular carcinoma (HCC) in animal models. Although previous studies showed that HCC patients had higher serum IL‐6 level at the time of diagnosis, it is unclear if the cytokine contributes to the development of HCC...

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Published in:International journal of cancer 2009-06, Vol.124 (12), p.2766-2770
Main Authors: Wong, Vincent Wai‐Sun, Yu, Jun, Cheng, Alfred Sze‐Lok, Wong, Grace Lai‐Hung, Chan, Hoi‐Yun, Chu, Eagle Siu‐Hong, Ng, Enders Kai‐On, Chan, Francis Ka‐Leung, Sung, Joseph Jao‐Yao, Chan, Henry Lik‐Yuen
Format: Article
Language:English
Subjects:
Biological and medical sciences
Biomarkers, Tumor - blood
Carcinoma, Hepatocellular - blood
Carcinoma, Hepatocellular - virology
Case-Control Studies
cytokines
False Positive Reactions
Female
fibrosis
Gastroenterology. Liver. Pancreas. Abdomen
hepatitis B
Hepatitis B virus - isolation & purification
Hepatitis B, Chronic - blood
Hepatitis B, Chronic - virology
Humans
Interleukin-6 - blood
interleukin‐6
liver neoplasms
Liver Neoplasms - blood
Liver Neoplasms - virology
Liver. Biliary tract. Portal circulation. Exocrine pancreas
Male
Medical sciences
Middle Aged
Neoplasm Staging
Predictive Value of Tests
Prognosis
Risk Factors
Sensitivity and Specificity
Tumors
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Summary:Increased interleukin‐6 (IL‐6) production is implicated in the pathogenesis of hepatocellular carcinoma (HCC) in animal models. Although previous studies showed that HCC patients had higher serum IL‐6 level at the time of diagnosis, it is unclear if the cytokine contributes to the development of HCC or is just a reaction to cancer. To address this question, we performed a nested case‐control study. Consecutive chronic hepatitis B patients were recruited from 1997 to 2000 and followed till 2008. Profiling of 27 cytokines, chemokines and growth factors was performed at baseline, date of peak alanine aminotransferase (ALT) level and the last visit. Thirty‐seven patients developed HCC at a median follow‐up of 62 months (interquartile range: 41–110). Serum IL‐6 was higher in patients with HCC than controls both during peak ALT and at the last visit (both p = 0.02). Patients with IL‐6 above 7 pg/ml during peak ALT had increased risk of HCC or death (adjusted hazard ratio 3.0; 95% confidence interval 1.2, 7.8; p = 0.02). The sensitivity, specificity, positive and negative predictive values of this cutoff to predict future HCC development were 70%, 73%, 72% and 71%, respectively. Combination of IL‐6 and AFP improved the sensitivity in diagnosing HCC or predicting future HCC development. In conclusion, high serum IL‐6 level predates the development of HCC in chronic hepatitis B patients, and has moderate accuracy in predicting future cancer. This may assist clinicians in selecting high‐risk patients for HCC surveillance program. © 2009 UICC
ISSN:0020-7136
1097-0215
DOI:10.1002/ijc.24281