title: Levels of 8-OxodG Predict Hepatobiliary Pathology in Opisthorchis viverrini Endemic Settings in Thailand.
abstract: Opisthorchis viverrini is distinct among helminth infections as it drives a chronic inflammatory response in the intrahepatic bile duct that progresses from advanced periductal fibrosis (APF) to cholangiocarcinoma (CCA). Extensive research shows that oxidative stress (OS) plays a critical role in the transition from chronic O. viverrini infection to CCA. OS also results in the excision of a modified DNA lesion (8-oxodG) into urine, the levels of which can be detected by immunoassay. Herein, we measured concentrations of urine 8-oxodG by immunoassay from the following four groups in the Khon Kaen Cancer Cohort study: (1) O. viverrini negative individuals, (2) O. viverrini positive individuals with no APF as determined by abdominal ultrasound, (3) O. viverrini positive individuals with APF as determined by abdominal ultrasound, and (4) O. viverrini induced cases of CCA. A logistic regression model was used to evaluate the utility of creatinine-adjusted urinary 8-oxodG among these groups, along with demographic, behavioral, and immunological risk factors. Receiver operating characteristic (ROC) curve analysis was used to evaluate the predictive accuracy of urinary 8-oxodG for APF and CCA. Elevated concentrations of 8-oxodG in urine positively associated with APF and CCA in a strongly dose-dependent manner. Urinary 8-oxodG concentrations also accurately predicted whether an individual presented with APF or CCA compared to O. viverrini infected individuals without these pathologies. In conclusion, urinary 8-oxodG is a robust 'candidate' biomarker of the progression of APF and CCA from chronic opisthorchiasis, which is indicative of the critical role that OS plays in both of these advanced hepatobiliary pathologies. The findings also confirm our previous observations that severe liver pathology occurs early and asymptomatically in residents of O. viverrini endemic regions, where individuals are infected for years (often decades) with this food-borne pathogen. These findings also contribute to an expanding literature on 8-oxodG in an easily accessible bodily fluid (e.g., urine) as a biomarker in the multistage process of inflammation, fibrogenesis, and infection-induced cancer.
authors.affiliation: Biomedical Science Program, Faculty of Graduate School, Khon Kaen University, Khon Kaen, Thailand; Department of Preclinical Science, Faculty of Medicine, Thammasat University, Pathumthani, Thailand.
authors.forename: Prasert
authors.initials: P
authors.lastname: Saichua
authors.affiliation: Department of Microbiology, Immunology and Tropical Medicine, and Research Center for Neglected Diseases of Poverty, School of Medicine & Health Sciences, George Washington University, Washington, D.C., United States of America.
authors.forename: Anna
authors.initials: A
authors.lastname: Yakovleva
authors.affiliation: Department of Microbiology, Immunology and Tropical Medicine, and Research Center for Neglected Diseases of Poverty, School of Medicine & Health Sciences, George Washington University, Washington, D.C., United States of America.
authors.forename: Christine
authors.initials: C
authors.lastname: Kamamia
authors.affiliation: Department of Microbiology, Immunology and Tropical Medicine, and Research Center for Neglected Diseases of Poverty, School of Medicine & Health Sciences, George Washington University, Washington, D.C., United States of America.
authors.forename: Amar R
authors.initials: AR
authors.lastname: Jariwala
authors.affiliation: Department of Clinical Microscopy, Faculty of Associated Medical Sciences, Khon Kaen University, Khon Kaen, Thailand.
authors.forename: Jiraporn
authors.initials: J
authors.lastname: Sithithaworn
authors.affiliation: Department of Pathology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand; Liver Fluke and Cholangiocarcinoma Research Center, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand.
authors.forename: Banchob
authors.initials: B
authors.lastname: Sripa
authors.affiliation: Department of Microbiology, Immunology and Tropical Medicine, and Research Center for Neglected Diseases of Poverty, School of Medicine & Health Sciences, George Washington University, Washington, D.C., United States of America.
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Brindley
authors.affiliation: Department of Parasitology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand.
authors.forename: Thewarach
authors.initials: T
authors.lastname: Laha
authors.affiliation: Department of Radiology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand.
authors.forename: Eimorn
authors.initials: E
authors.lastname: Mairiang
authors.affiliation: Department of Pathology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand; Liver Fluke and Cholangiocarcinoma Research Center, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand.
authors.forename: Chawalit
authors.initials: C
authors.lastname: Pairojkul
authors.affiliation: Liver Fluke and Cholangiocarcinoma Research Center, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand; Department of Surgery, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand.
authors.forename: Narong
authors.initials: N
authors.lastname: Khuntikeo
authors.affiliation: Infections Disease Program, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
authors.forename: Jason
authors.initials: J
authors.lastname: Mulvenna
authors.affiliation: Liver Fluke and Cholangiocarcinoma Research Center, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand; Department of Parasitology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand.
authors.forename: Paiboon
authors.initials: P
authors.lastname: Sithithaworn
authors.affiliation: Department of Microbiology, Immunology and Tropical Medicine, and Research Center for Neglected Diseases of Poverty, School of Medicine & Health Sciences, George Washington University, Washington, D.C., United States of America.
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Bethony
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D000328:Adult; D000818:Animals; D001659:Biliary Tract / Q000469:parasitology* / Q000473:pathology; D015415:Biomarkers / Q000652:urine; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000652:urine; D019353:Endemic Diseases; D005243:Feces / Q000469:parasitology; D005260:Female; D006801:Humans; D008103:Liver Cirrhosis / Q000469:parasitology* / Q000473:pathology; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D009889:Opisthorchiasis / Q000453:epidemiology / Q000469:parasitology* / Q000473:pathology; D009891:Opisthorchis; D013785:Thailand / Q000453:epidemiology; D055815:Young Adult
chemical_list: D015415:Biomarkers; D000080242:8-Hydroxy-2'-Deoxyguanosine; D003849:Deoxyguanosine