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

Authors

Banchob Sripa, Khon Kaen University School of Medicine, Khon Kaen, Thailand
Bandit Thinkhamrop, Khon Kaen University School of Medicine, Khon Kaen, Thailand
Eimorn Mairiang, Khon Kaen University School of Medicine, Khon Kaen, Thailand
Thewarach Laha, Khon Kaen University School of Medicine, Khon Kaen, Thailand
Sasithorn Kaewkes, Khon Kaen University School of Medicine, Khon Kaen, Thailand
Paiboon Sithithaworn, Khon Kaen University School of Medicine, Khon Kaen, Thailand
Maria V. Periago, Instituto René Rachou, Belo Horizonte, Minas Gerais, Brazil
Vajarabhongsa Bhudhisawasdi, Khon Kaen University School of Medicine, Khon Kaen, Thailand
Ponlapat Yonglitthipagon, Khon Kaen University School of Medicine, Khon Kaen, Thailand
Jason Mulvenna, James Cook University, Cairns, QLD, Australia
Paul J. Brindley, George Washington UniversityFollow
Alex Loukas, James Cook University, Cairns, QLD, AustraliaFollow
Jeffrey M. Bethony, George Washington UniversityFollow

Document Type

Journal Article

Publication Date

5-2012

Journal

PLoS Neglected Tropical Diseases

Volume

Volume 6, Issue 5

Inclusive Pages

Article number e1654

Keywords

Bile Duct Diseases--epidemiology; Cholangiocarcinoma--epidemiology; Fibrosis--epidemiology; Interleukin-6--blood; Opisthorchiasis--complications; Opisthorchis--pathogenicity; Plasma--chemistry

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. viverriniinfection.

Comments

Reproduced with permission of PLoS Neglected Tropical Diseases

Creative Commons License

This work is licensed under a Creative Commons Attribution 3.0 License.

APA Citation

Sripa, B., Thinkhamrop, B., Mairiang, E., Laha, T., Kaewkes, S., Sithithaworn, P., Periago, M.V., Bhudhisawasdi, V., Yonglitthipagon, P., Mulvenna, J., Brindley, P.J., Loukas, A., Bethony, J. 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.

Peer Reviewed

1

Open Access

1