Development of preclinical diagnostic tools of hepatobiliary tumors associated with Opisthorchis felineus infection in population of endemic regions

According to the official medical statistics, the incidence of hepatobiliary tumors (including cholangiocarcinoma) in the Tomsk region was 9.31 cases per 100,000 population in 2011-2013, which was twice the average in Russia [Fedorova OS, Kovshirina Yu.V., et al., 2017]. Cholangiocarcinoma is a group of intra- and / or extrahepatic bile ducts cancer with high mortality due to its aggressiveness, lack of specific symptoms and / or prolonged asymptomatic course and resistance to therapy [Bridgewater J, Galle PR, Khan SA et al., 2014]. One of the significant risk factors for liver cancer is the high prevalence of parasitic infection caused by liver fluke O. felineus in Western Siberia, whose carcinogenic potential has been demonstrated in a number of experimental studies in animal models of the disease, as well as in research on autopsy material, surgical data [Gouveia MJ, Pakharukova MY, et al., 2017; Brazhnikov N.A. et al., 2002; Maksimova GA, Pakharukova MY, 2017; Bychkov V.G., 2003; Kovshirina YV, Fedorova OS, Kovshirina AE et al, in press, 2018]. In this regard, it is necessary to develop diagnostic tools allowed timely detection of severe hepatobiliary diseases (including cancer) associated with opisthorchiasis in order to jugulate it and improve the prognosis for patients in endemic regions. In this way, the aim of this project is creation a diagnostic tools for early preclinical diagnostics of the hepatobiliary tumors (cholangiocarcinoma) in patients with chronic O. felineus infection in endemic regions. For these aims a comprehensive fundamental research will be performed, including evaluation of biochemical measures (lactate, alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transferase, alkaline phosphatase, glucose, direct and indirect bilirubin, high and low density lipoproteins, triacylglycers, as well as low-density lipotropes. Immunological parameters (TGFb) and tumor markers (CA 19-9, СYFRA 21-1) in serum samples obtained from patients with O. felineus infection having periductal fibrosis and without it, patients with cholangiocarcinoma and individuals without opisthorchiasis and bile ducts cancer. Statistical analysis was carried out using the programming language R version 3.6.1. The study results indicate that ultrasound of the liver and biliary system with the assessment of opistorchosis-associated periductal fibrosis together with the determination of biochemical indicators (alkaline phosphatase, direct bilirubin, AST, glucose), as well as oncomarker CA 19-9, as predictors of fibrosis, can be used as an algorithm for early preclinical diagnosis of malignant tumors of the hepatobiliary system (cholangiocarcinoma) against the background of chronic infection O. felineus, in the population of endemic regions.