Diagnosis of Indolent Clonorchis sinensis and Opisthorchis viverrini Infections as Risk Factors for Cholangiocarcinoma: An Unmet Medical Need.

Abstract

Cholangiocarcinoma is a highly aggressive cancer of the biliary tract epithelium. This form of cancer is prevalent in Asia, and recent reports show that its incidence is relatively rare but increasing in the United States. Although risk factors for cholangiocarcinoma have yet to be elucidated, a growing body of literature suggests chronic infection of genetically susceptible individuals with the food-borne zoonotic trematodes Clonorchis sinensis (C sinensis) and Opisthorchis viverrini (O viverrini) may play a role. Although most infected people remain asymptomatic, untreated indolent infections with C sinensis and O viverrini may persist in peripheral intrahepatic bile ducts for almost 30 years. During this period, the trematodes' feeding activities and their excretory-secretory products may damage the bile duct epithelium and promote local inflammation. These pathological processes could then provoke epithelial desquamation, adenomatous hyperplasia, goblet cell metaplasia, periductal fibrosis, and granuloma formation that are conducive to the initiation and progression of cholangiocarcinoma in genetically susceptible people. The International Agency for Research on Cancer has determined that there is sufficient evidence in humans for the carcinogenicity of chronic infections with C sinensis and O viverrini. Timely serodiagnosis of indolent C sinensis and O viverrini infections is important as these parasites may be a risk factor for cholangiocarcinoma in veterans who served in Vietnam. About 774,000 living Americans served in Vietnam and there is an urgent need to develop sensitive and specific serologic assays to detect both acute and indolent infections. We posit that testing and treatment of high-risk populations could lead to earlier detection and treatment of cholangiocarcinoma, leading to improved overall survival.