Effect of Opisthorchis felineus infection and dimethylnitrosamine administration on the induction of cholangiocarcinoma in Syrian hamsters.

The food-borne liver trematode Opisthorchis felineus is an emerging source of biliary tract diseases on the territory of the former Soviet Union and Eastern Europe. This parasite along with trematodes Opisthorchis viverrini and Clonorchis sinensis belong to the triad of epidemiologically important liver flukes of the Opisthorchiidae family. It is known that O. viverrini and C. sinensis are the main risk factors of cholangiocarcinoma (CCA) in the endemic regions. The carcinogenic potential of O. felineus has not been well researched because of the absence of systematic pathomorphological, clinical, and epidemiological studies on O. felineus opisthorchiasis. In the present study, we show the results of detailed histopathological analysis and comprehensive evaluation of inflammation, bile duct dysplasia, periductal fibrosis, bile duct hyperplasia, bile duct proliferation, egg granuloma, cysts, cholangiofibrosis, and CCA from 10 to 30 weeks following infection of Syrian hamsters with O. felineus accompanied by oral administration of dimethylnitrosamine (DMN). The results revealed that O. felineus contributes to bile duct cancer development in the hamster model. During the combined action of O. felineus and DMN, morphological features of the liver underwent dramatic changes at the cellular and organ levels. Already in the early stages of the experiment, we observed extensive periductal fibrosis, active inflammation, proliferation of the bile duct, bile duct dysplasia and egg granulomas. Later, against the background of all these changes, cholangiofibrosis and CCA were found. Our work is the first step in the study of carcinogenic potential of O. felineus. Obtained data indicate the risk of CCA of patients having chronic O. felineus opisthorchiasis, and underscore the need for the development of programs for control of this helminthiasis.