Liver Flukes and Cholangiocarcinoma: Mechanism of Carcinogenesis

Lee, Seung Ok; Kim, Seong Hun

Abstract

It has been clarified that chronic infection with viruses such as hepatitis B virus, bacteria such as Helicobacter pylori and parasites contribute to carcinogenesis in human. Three helminth infections have been classified as definitely carcinogenic to humans (group I carcinogens), namely Schistosoma haematobium, which is associated with urinary bladder cancer and liver flukes Clonorchis sinensis and Opisthorchis viverrini associated with cholangiocarcinoma of the liver. Opisthorchis viverrini which has been extensively studied the association with cholangiocarcinoma is endemic in Southeast Asian countries including Thailand, Vietnam and Cambodia. Clonorchis sinensis infection which is common in rural areas of Korea and China has also been reported its definite association with cholangiocarcinoma. Carcinogenesis associated with liver flukes infections is a complex process hard to be studied because of long latency period and numerous other factors can play a role although chronic inflammation has been known as a key feature. Mechanical injury from the activities of migrating and sucking flukes contributes to biliary damage and chronic inflammation. The liver fluke also secretes or excretes metabolic products, some of which are highly immunogenic, toxic and promoting biliary epithelial cell proliferation. Host immune responses and immunopathological processes are also likely associated with chronic inflammation and carcinogenesis. Escape from host anti-tumor immune response and shift to Th2 response of Th1-Th2 balance are related with carcinogenesis. Biliary cell and its DNA damage can be induced by oxygen free radicals such as nitric oxide released from effector cells activated by inflammatory cytokines. Exogenous carcinogen suchas nitrosamine seemed also closely related with cholangiocarcinoma development in liver fluke infected individuals. In this paper, various and stepwise mechanisms of carcinogenesis by liver flukes and its potential targets can be intervene were reviewed.