Volume 98, Issue 6
  • ISSN: 0002-9637
  • E-ISSN: 1476-1645



Previous studies demonstrated that urinary 8-oxodG is a predictive biomarker for (OV)–associated hepatobiliary disease (HBD) and cholangiocarcinoma (CCA). This study examined the effects of praziquantel treatment on the profile of urinary 8-oxodG in relation to HBD status. Infection with OV, levels of urinary 8-oxodG, and HBD status in terms of periductal fibrosis (PDF) assessed by abdominal ultrasonography (US) were monitored and compared in cohorts of participants in Khon Kaen, Thailand, before and 1 year after praziquantel treatment. Urinary 8-oxodG levels significantly decreased after treatment compared with the baseline level in OV-infected participants who had no HBD (PDF negative; PDF−ve) ( = 14). Levels of 8-oxodG were unchanged after treatment in OV-infected subjects (OV+ve) who had positive PDF ( = 52). Within the positive PDF (PDF+ve) group who became PDF−ve after treatment, there was no significant change in 8-oxodG levels between pre-and posttreatment (reversible PDF = 65.3%). In those who had persistent PDF+ve at both ultrasound sampling points, there was no significant difference in urinary 8-oxodG levels between pre- and posttreatment (persistent PDF = 34.6%). Based on a logistic regression model and receiver operation curve analysis, the increase of 8-oxodG levels was found to be associated with increasing risk of PDF. Measurement of urinary 8-oxodG and US increased the likelihood of discovering persistent PDF, which is a predictable condition for the patients at risk of OV-associated CCA. To identify high-risk individuals for CCA, it is useful to perform US in combination with urinary 8-oxodG measurement.


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  1. Elkins DB, Haswell-Elkins MR, Mairiang E, Mairiang P, Sithithaworn P, Kaewkes S, Bhudhisawasdi V, Uttaravichien T, , 1990. A high frequency of hepatobiliary disease and suspected cholangiocarcinoma associated with heavy Opisthorchis viverrini infection in a small community in north-east Thailand. Trans R Soc Trop Med Hyg 84: 715719. [Google Scholar]
  2. IARC, 1994. Infection with liver flukes (Opisthorchis viverrivi, Opisthorchis felineus and Clonorchis sinensis). IARC Monogr Eval Carcinog Risks Hum 61: 121175. [Google Scholar]
  3. Mairiang E, Elkins DB, Mairiang P, Chaiyakum J, Chamadol N, Loapaiboon V, Posri S, Sithithaworn P, Haswell-Elkins M, , 1992. Relationship between intensity of Opisthorchis viverrini infection and hepatobiliary disease detected by ultrasonography. J Gastroenterol Hepatol 7: 1721. [Google Scholar]
  4. Thanan R, Oikawa S, Hiraku Y, Ohnishi S, Ma N, Pinlaor S, Yongvanit P, Kawanishi S, Murata M, , 2015. Oxidative stress and its significant roles in neurodegenerative diseases and cancer. Int J Mol Sci 16: 193217. [Google Scholar]
  5. Evans MD, Saparbaev M, Cooke MS, , 2010. DNA repair and the origins of urinary oxidized 2′-deoxyribonucleosides. Mutagenesis 25: 433442. [Google Scholar]
  6. Murata M, Thanan R, Ma N, Kawanishi S, , 2012. Role of nitrative and oxidative DNA damage in inflammation-related carcinogenesis. J Biomed Biotechnol 2012: 623019. [Google Scholar]
  7. Wynn TA, , 2008. Cellular and molecular mechanisms of fibrosis. J Pathol 214: 199210. [Google Scholar]
  8. Yongvanit P, Pinlaor S, Bartsch H, , 2012. Oxidative and nitrative DNA damage: key events in opisthorchiasis-induced carcinogenesis. Parasitol Int 61: 130135. [Google Scholar]
  9. Saichua P, 2015. Levels of 8-OxodG predict hepatobiliary pathology in Opisthorchis viverrini endemic settings in Thailand. PLoS Negl Trop Dis 9: e0003949. [Google Scholar]
  10. Thanan R, Murata M, Pinlaor S, Sithithaworn P, Khuntikeo N, Tangkanakul W, Hiraku Y, Oikawa S, Yongvanit P, Kawanishi S, , 2008. Urinary 8-oxo-7,8-dihydro-2′-deoxyguanosine in patients with parasite infection and effect of antiparasitic drug in relation to cholangiocarcinogenesis. Cancer Epidemiol Biomarkers Prev 17: 518524. [Google Scholar]
  11. Elkins DB, Mairiang E, Sithithaworn P, Mairiang P, Chaiyakum J, Chamadol N, Loapaiboon V, Haswell-Elkins MR, , 1996. Cross-sectional patterns of hepatobiliary abnormalities and possible precursor conditions of cholangiocarcinoma associated with Opisthorchis viverrini infection in humans. Am J Trop Med Hyg 55: 295301. [Google Scholar]
  12. Mairiang E, Laha T, Bethony JM, Thinkhamrop B, Kaewkes S, Sithithaworn P, Tesana S, Loukas A, Brindley PJ, Sripa B, , 2012. Ultrasonography assessment of hepatobiliary abnormalities in 3359 subjects with Opisthorchis viverrini infection in endemic areas of Thailand. Parasitol Int 61: 208211. [Google Scholar]
  13. Mairiang E, Mairiang P, , 2003. Clinical manifestation of opisthorchiasis and treatment. Acta Trop 88: 221227. [Google Scholar]
  14. Chamadol N, Pairojkul C, Khuntikeo N, Laopaiboon V, Loilome W, Sithithaworn P, Yongvanit P, , 2014. Histological confirmation of periductal fibrosis from ultrasound diagnosis in cholangiocarcinoma patients. J Hepatobiliary Pancreat Sci 21: 316322. [Google Scholar]
  15. Kaewkes S, Elkins DB, Sithithaworn P, Haswell-Elkins MR, , 1991. Comparative studies on the morphology of the eggs of Opisthorchis viverrini and lecithodendriid trematodes. Southeast Asian J Trop Med Public Health 22: 623630. [Google Scholar]
  16. Tesana S, Srisawangwonk T, Kaewkes S, Sithithaworn P, Kanla P, Arunyanart C, , 1991. Eggshell morphology of the small eggs of human trematodes in Thailand. Southeast Asian J Trop Med Public Health 22: 631636. [Google Scholar]
  17. Songserm N, Promthet S, Wiangnon S, Sithithaworn P, , 2012. Prevalence and co-infection of intestinal parasites among Thai rural residents at high-risk of developing cholangiocarcinoma: a cross-sectional study in a prospective cohort study. Asian Pac J Cancer Prev 13: 61756179. [Google Scholar]
  18. Xia Y, Wong LY, Bunker BC, Bernert JT, , 2014. Comparison of creatinine and specific gravity for hydration corrections on measurement of the tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) in urine. J Clin Lab Anal 28: 353363. [Google Scholar]
  19. Sripa B, Mairiang E, Thinkhamrop B, Laha T, Kaewkes S, Sithithaworn P, Tessana S, Loukas A, Brindley PJ, Bethony JM, , 2009. Advanced periductal fibrosis from infection with the carcinogenic human liver fluke Opisthorchis viverrini correlates with elevated levels of interleukin-6. Hepatology 50: 12731281. [Google Scholar]
  20. Sripa B, Brindley PJ, Mulvenna J, Laha T, Smout MJ, Mairiang E, Bethony JM, Loukas A, , 2012. The tumorigenic liver fluke Opisthorchis viverrini—multiple pathways to cancer. Trends Parasitol 28: 395407. [Google Scholar]
  21. Sripa B, Kaewkes S, , 2000. Localisation of parasite antigens and inflammatory responses in experimental opisthorchiasis. Int J Parasitol 30: 735740. [Google Scholar]
  22. Worasith C, 2015. Advances in the diagnosis of human opisthorchiasis: development of Opisthorchis viverrini antigen detection in urine. PLoS Negl Trop Dis 9: e0004157. [Google Scholar]
  23. Wishahi M, Zakarya A, Hamamm O, Abdel-Rasol M, Badawy H, Elganzoury H, Ismail M, Elkhouly A, Meheina A, , 2014. Impact of density of schistosomal antigen expression in urinary bladder tissue on the stratification, cell type, and staging, and prognosis of carcinoma of the bladder in Egyptian patients. Infect Agent Cancer 9: 21. [Google Scholar]
  24. Sundararaj KP, Samuvel DJ, Li Y, Sanders JJ, Lopes-Virella MF, Huang Y, , 2009. Interleukin-6 released from fibroblasts is essential for up-regulation of matrix metalloproteinase-1 expression by U937 macrophages in coculture: cross-talking between fibroblasts and U937 macrophages exposed to high glucose. J Biol Chem 284: 1371413724. [Google Scholar]
  25. Martins-Leite P, Gazzinelli G, Alves-Oliveira LF, Gazzinelli A, Malaquias LC, Correa-Oliveira R, Teixeira-Carvalho A, Silveira AM, , 2008. Effect of chemotherapy with praziquantel on the production of cytokines and morbidity associated with schistosomiasis mansoni. Antimicrob Agents Chemother 52: 27802786. [Google Scholar]
  26. Deenonpoe R, Chomvarin C, Pairojkul C, Chamgramol Y, Loukas A, Brindley PJ, Sripa B, , 2015. The carcinogenic liver fluke Opisthorchis viverrini is a reservoir for species of Helicobacter. Asian Pac J Cancer Prev 16: 17511758. [Google Scholar]
  27. Loft S, Vistisen K, Ewertz M, Tjonneland A, Overvad K, Poulsen HE, , 1992. Oxidative DNA damage estimated by 8-hydroxydeoxyguanosine excretion in humans: influence of smoking, gender and body mass index. Carcinogenesis 13: 22412247. [Google Scholar]
  28. Pinlaor S, 2006. iNOS-dependent DNA damage via NF-kappaB expression in hamsters infected with Opisthorchis viverrini and its suppression by the antihelminthic drug praziquantel. Int J Cancer 119: 10671072. [Google Scholar]
  29. Mairiang E, Haswell-Elkins MR, Mairiang P, Sithithaworn P, Elkins DB, , 1993. Reversal of biliary tract abnormalities associated with Opisthorchis viverrini infection following praziquantel treatment. Trans R Soc Trop Med Hyg 87: 194197. [Google Scholar]
  30. Chai JY, , 2013. Praziquantel treatment in trematode and cestode infections: an update. Infect Chemother 45: 3243. [Google Scholar]
  31. Lovis L, 2012. Efficacy of praziquantel against Schistosoma mekongi and Opisthorchis viverrini: a randomized, single-blinded dose-comparison trial. PLoS Negl Trop Dis 6: e1726. [Google Scholar]
  32. Saengsawang P, Promthet S, Bradshaw P, , 2013. Infection with Opisthorchis viverrini and use of praziquantel among a working-age population in northeast Thailand. Asian Pac J Cancer Prev 14: 29632966. [Google Scholar]
  33. Miller RC, Brindle E, Holman DJ, Shofer J, Klein NA, Soules MR, O’Connor KA, , 2004. Comparison of specific gravity and creatinine for normalizing urinary reproductive hormone concentrations. Clin Chem 50: 924932. [Google Scholar]
  34. Hall Moran V, Leathard HL, Coley J, , 2001. Urinary hormone levels during the natural menstrual cycle: the effect of age. J Endocrinol 170: 157164. [Google Scholar]
  35. Worsfold M, Davie MW, Haddaway MJ, , 1999. Age-related changes in body composition, hydroxyproline, and creatinine excretion in normal women. Calcif Tissue Int 64: 4044. [Google Scholar]
  36. Wagner BD, Accurso FJ, Laguna TA, , 2010. The applicability of urinary creatinine as a method of specimen normalization in the cystic fibrosis population. J Cyst Fibros 9: 212216. [Google Scholar]
  37. Suwazono Y, Akesson A, Alfven T, Jarup L, Vahter M, , 2005. Creatinine versus specific gravity-adjusted urinary cadmium concentrations. Biomarkers 10: 117126. [Google Scholar]
  38. Chamadol N, Laopaiboon V, Srinakarin J, Loilome W, Yongvanit P, Thinkhamrop B, Khuntikeo N, , 2017. Teleconsultation ultrasonography: a new weapon to combat cholangiocarcinoma. ESMO Open 2: e000231. [Google Scholar]
  39. O’Connor OJ, O’Neill S, Maher MM, , 2011. Imaging of biliary tract disease. AJR Am J Roentgenol 197: W551W558. [Google Scholar]
  40. Kaneko K, Kimata T, Tsuji S, Ohashi A, Imai Y, Sudo H, Kitamura N, , 2012. Measurement of urinary 8-oxo-7,8-dihydro-2-deoxyguanosine in a novel point-of-care testing device to assess oxidative stress in children. Clin Chim Acta 413: 18221826. [Google Scholar]
  41. Khuntikeo N, CASCAP Investigators , 2015. Cohort profile: cholangiocarcinoma screening and care program (CASCAP). BMC Cancer 15: 459. [Google Scholar]

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  • Received : 13 Dec 2017
  • Accepted : 20 Feb 2018
  • Published online : 09 Apr 2018

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