Advanced Periductal Fibrosis from Infection with the... : Hepatology (original) (raw)

Liver Biology/Pathobiology

Advanced Periductal Fibrosis from Infection with the Carcinogenic Human Liver Fluke Opisthorchis viverrini Correlates with Elevated Levels of Interleukin-6†‡

Sripa, Banchob1; Mairiang, Eimorn2; Thinkhamrop, Bandit3; Laha, Thewarach4; Kaewkes, Sasithorn4; Sithithaworn, Paiboon4; Tessana, Smarn4; Loukas, Alex5; Brindley, Paul J.6; Bethony, Jeffrey M.1,*,§

1 Department of Pathology, Khon Kaen University School of Medicine, Khon Kaen, Thailand

2 Department of Radiology, Khon Kaen University School of Medicine, Khon Kaen, Thailand

3 Department of Epidemiology and Biostatistics, Khon Kaen University School of Public Health, Khon Kaen, Thailand

4 Department of Parasitology, Khon Kaen University School of Medicine, Khon Kaen, Thailand

5 Division of Infectious Diseases, Queensland Institute of Medical Research, Brisbane, Queensland, Australia

6 Department of Microbiology, Immunology & Tropical Medicine, George Washington University Medical Center, Washington, DC

*Address reprint requests to: 2300 Eye Street NW, Clinical Immunology Laboratory, Ross Hall, Washington, DC 20037

E-mail:[email protected]

Received 13 March 2009; Accepted 11 June 2009.

Published online in Wiley InterScience (www.interscience.wiley.com)..

Grant sponsor: National Institute of Allergy and Infectious Diseases; Grant Number: UO1AI065871.

Potential conflict of interest: Nothing to report.

The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Allergy and Infectious Disease or the National Institutes of Health.

§fax: 202-994-2913

Additional supporting information may be found in the online version of this article.

Abstract

More than 750 million people are at risk of infection with foodborne liver flukes. Opisthorchis viverrini is considered among the most important of these parasites, due to its strong association with cholangiocarcinoma (CCA). O. viverrini infection results in a chronic inflammatory challenge to the host, which can lead to advanced, pathogen-specific disease sequelae including obstructive jaundice, hepatomegaly, cholecystitis, as well as CCA. However, before disease sequelae are apparent, important inflammatory changes to the liver can be detected early during O. viverrini infection. In a case-control study involving 328 men and women with O. viverrini infection, we determined the presence of advanced periductal fibrosis in asymptomatic, O. viverrini-infected individuals and then measured cytokine responses to O. viverrini excretory/secretory products (ES). In the 200 participants with advanced periductal fibrosis (cases), levels of interleukin-6 (IL-6) to O. viverrini ES were 8 times higher than levels of the 128 O. viverrini -infected individuals without advanced periductal fibrosis (controls). Moreover, elevated IL-6 to parasite ES was associated with increased risk of advanced periductal fibrosis by 63% in a model adjusted for sex and age. The risk of advanced periductal fibrosis was also found to increase with higher levels of IL-6: individuals in the third quartile of IL-6-ES production had a 127% higher risk of developing advanced periductal fibrosis than individuals in the first quartile of IL-6 production. O. viverrini -infected individuals with advanced periductal fibrosis showed other hepatobiliary abnormalities, including reduced gallbladder contractility and the presence of gallbladder sludge.

Conclusion:

These data strongly implicate a role for parasite-specific IL-6 in the pathogenesis of advanced periductal fibrosis in opisthorchiasis, with possible links to other hepatobiliary abnormalities, including CCA. (Hepatology 2009.)

Copyright © 2009 American Association for the Study of Liver Diseases.