During chronic opisthorchiasis, pathogenesis is manifested in a series of well-defined stages as the normal tissue architecture of the biliary epithelium is progressively remodeled by the chronic inflammatory response from repeated injury sustained by the biliary epithelium from a combination ofthe mechanical, toxic, and immune mechanisms of the fluke in the bile duct. As individuals are infected with O. viverrini for many years (often a lifetime), a persistent cycle of tissue damage and repair takes place in the intrahepatic biliary ducts, creating a chronic inflammatory milieu that stimulates periductal fibrogenesis and provides the """"""""smoldering and polarized"""""""" inflammatory basis for malignant transformation of biliary epithelial cells to cholangiocarcinoma (CCA). In project 1, we hypothesize the existence of a pro-inflammatory phenotype which is characterized by a inflammatory cytokine dysregulation such that, even after removal ofthe pathogen by PZQ, individuals with the pro-inflammatory phenotype continue to produce high levels of IL-6 and an unreversed (i.e., persistent) form of Advanced Periductal Fibrosis (APF). We further hypothesize that this persistent APF provides the basis for malignant transformation to CCA. Project 1 ofthe TMRC will focus on the processes involved in this chronic inflammatory phenotype and the progression from infection to persistent APF and eventually to malignant transformation (CCA) by undertaking the following specific aims: (1) continuing our a community-based cohort study for the risk factors associated with Advanced Periductal Fibrosis in villages with high O. viverrini transmission along the Chi River basin in Khon Kaen, Thailand to stratify infected individuals into those with """"""""resolved"""""""" and """"""""persistent"""""""" Advanced Periductal Fibrosis;(2) to determine the host inflammatory cytokine signaling pathways, such as the IL-6 signaling pathways, induced during chronic O. viverrini infection on the risk of progressing either resolved or persistent advanced periductal fibrosis, and bile duct cancer;and (3) examine the genetic diversity ofthe O. viverrini parasite by microsatellite DNA analysis and its association with resolved and persistent forms advanced periductal fibrosis. .

Public Health Relevance

Individuals residents in O. viverrini endemic areas can remain infected for a lifetime. However, only 25% of O. viverrini-infected individuals develop periductal fibrosis and 1 % progress to CCA. The observation that individuals living under similar transmission conditions show differing rates of APF and CCA indicates a strong role for diverse host and parasite factors in the disease process.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Specialized Center (P50)
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Special Emphasis Panel (ZAI1-AWA-M)
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Khon Kaen University
Khon Kaen
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Teimoori, Salma; Arimatsu, Yuji; Laha, Thewarach et al. (2017) Chicken IgY-based coproantigen capture ELISA for diagnosis of human opisthorchiasis. Parasitol Int 66:443-447
Saltykova, Irina V; Ogorodova, Ludmilla M; Ivanov, Vladimir V et al. (2017) Carbonyl stress phenomena during chronic infection with Opisthorchis felineus. Parasitol Int 66:453-457
Gouveia, Maria João; Pakharukova, Maria Y; Laha, Thewarach et al. (2017) Infection with Opisthorchis felineus induces intraepithelial neoplasia of the biliary tract in a rodent model. Carcinogenesis 38:929-937
Surapaitoon, Arpa; Suttiprapa, Sutas; Mairiang, Eimorn et al. (2017) Subsets of Inflammatory Cytokine Gene Polymorphisms are Associated with Risk of Carcinogenic Liver Fluke Opisthorchis viverrini-Associated Advanced Periductal Fibrosis and Cholangiocarcinoma. Korean J Parasitol 55:295-304
Surapaitoon, Arpa; Suttiprapa, Sutas; Khuntikeo, Narong et al. (2017) Cytokine profiles in Opisthorchis viverrini stimulated peripheral blood mononuclear cells from cholangiocarcinoma patients. Parasitol Int 66:889-892
Potriquet, Jeremy; Laohaviroj, Marut; Bethony, Jeffrey M et al. (2017) A modified FASP protocol for high-throughput preparation of protein samples for mass spectrometry. PLoS One 12:e0175967
Chaiyadet, Sujittra; Smout, Michael; Laha, Thewarach et al. (2017) Proteomic characterization of the internalization of Opisthorchis viverrini excretory/secretory products in human cells. Parasitol Int 66:494-502
Deenonpoe, Raksawan; Mairiang, Eimorn; Mairiang, Pisaln et al. (2017) Elevated prevalence of Helicobacter species and virulence factors in opisthorchiasis and associated hepatobiliary disease. Sci Rep 7:42744
van Tong, Hoang; Brindley, Paul J; Meyer, Christian G et al. (2017) Parasite Infection, Carcinogenesis and Human Malignancy. EBioMedicine 15:12-23
Sripa, Banchob; Deenonpoe, Raksawan; Brindley, Paul J (2017) Co-infections with liver fluke and Helicobacter species: A paradigm change in pathogenesis of opisthorchiasis and cholangiocarcinoma? Parasitol Int 66:383-389

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