Elevated plasma IL-6 associates with increased risk of advanced fibrosis and cholangiocarcinoma in individuals infected by Opisthorchis viverrini

Sripa, Banchob, Thinkhamrop, Bandit, Mairiang, Eimorn, Laha, Thewarach, Kaewkes, Sasithorn, Sithithaworn, Paiboon, Periago, Maria Victoria, Bhudhisawasdi, Vajarabhongsa, Yonglitthipagon, Ponlapat, Mulvenna, Jason, Brindley, Paul J., Loukas, Alex, and Bethony, Jeffrey M. (2012) Elevated plasma IL-6 associates with increased risk of advanced fibrosis and cholangiocarcinoma in individuals infected by Opisthorchis viverrini. PLoS Neglected Tropical Diseases, 6 (5). e1654. pp. 1-9.

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Abstract

Opisthorchis viverrini is considered among the most important of the food-borne trematodes due to its strong association with advanced periductal fibrosis and bile duct cancer (cholangiocarcinoma). We investigated the relationship between plasma levels of Interleukin (IL)-6 and the risk of developing advanced fibrosis and bile duct cancer from chronic Opisthorchis infection. We show that IL-6 circulates in plasma at concentrations 58 times higher in individuals with advanced fibrosis than age, sex, and nearest-neighbor matched controls and 221 times higher in individuals with bile duct cancer than controls. We also observed a dose-response relationship between increasing levels of plasma IL-6 and increasing risk of advanced fibrosis and bile duct cancer; for example, in age and sex adjusted analyses, individuals with the highest quartiles of plasma IL-6 had a 19 times greater risk of developing advanced periductal fibrosis and a 150 times greater risk of developing of bile duct cancer than individuals with no detectable level of plasma IL-6. Finally, we show that a single plasma IL-6 measurement has excellent positive predictive value for the detection of both advanced bile duct fibrosis and bile duct cancer in regions with high O. viverrini transmission. These data support our hypothesis that common mechanisms drive bile duct fibrosis and bile duct tumorogenesis from chronic O. viverrini infection. Our study also adds a unique aspect to the literature on circulating levels of IL-6 as an immune marker of hepatobiliary pathology by showing that high levels of circulating IL-6 in plasma are not related to infection with O. viverrini, but to the development of the advanced and often lethal pathologies resulting from chronic O. viverrini infection.

Item ID: 22296
Item Type: Article (Research - C1)
ISSN: 1935-2735
Funders: National Institute of Allergy and Infectious Disease (NIAID), National Cancer Institute (NCI), National Institute of Health (NIH), USA
Date Deposited: 11 Jul 2012 09:35
FoR Codes: 11 MEDICAL AND HEALTH SCIENCES > 1112 Oncology and Carcinogenesis > 111202 Cancer Diagnosis @ 34%
11 MEDICAL AND HEALTH SCIENCES > 1103 Clinical Sciences > 110302 Clinical Chemistry (diagnostics) @ 33%
11 MEDICAL AND HEALTH SCIENCES > 1107 Immunology > 110705 Humoural Immunology and Immunochemistry @ 33%
SEO Codes: 92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920102 Cancer and Related Disorders @ 50%
92 HEALTH > 9202 Health and Support Services > 920203 Diagnostic Methods @ 50%
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