Cholangiocarcinoma in experimental hamsters with long-standing Opisthorchis viverrini infection.

Liver fluke infection of Opisthorchis viverrini (O. viverrini) is closely associated with several hepatobiliary diseases including cholangiocarcinoma (CCA), but no reports have described these diseases in chronic and long-standing experimental opisthorchiasis in hamsters more than 10 months of age. A longer period of infection could induce different pathological lesions. To prove the hypothesis, we therefore sequentially investigated histological changes of the hepatobiliary system in 4 groups of hamsters: O. viverrini infection (OV group) for up to 20 months; O. viverrini infection combined with short-term DMN (OV+DMN group) until 7 months; long-term treatment with DMN (DMN group) to 7 months; and normal controls for up to 20 months. Pathological changes in hamsters of the OV group gradually increased. Induction of CCA in this study was apparent with all three protocols. Importantly, this is the first report of CCA-induction in hamsters solely with long-term opisthorchiasis for up to 20 months. Although the histopathology of CCA in the OV group showed some differences in appearance from the OV+DMN and DMN groups, overall, O. viverrini itself can really induce CCA. In addition, this study confirms the previous studies both in vitro and in vivo on of effects of parasites and their metabolic products inducing cell proliferation, resulting in cholangiocarcinogenesis.