Associations of Liver Fluke Infection and Cholangiocarcinoma: A Scoping Review

Cholangiocarcinoma (CCa) is a highly lethal malignancy of biliary tract epithelial cells. Liver fluke infection is one of the well-known causes of CCa in endemic areas of Southeast Asian and Western Pacific regions. Multistep processes underlie carcinogenesis induced by chronic infection with the fish-borne liver fluke. Mechanical injury from fluke feeding and migrating in the bile duct causes damage to the bile duct epithelial cells. The excretory or secretory product of a parasite called OvGRN-1 is internalized by human cholangiocytes and induces changes in gene and protein expression associated with wound healing and cancer pathways. Inflammatory cytokines and their gene polymorphisms may also be linked to biliary pathologies. High plasma levels of interleukin 6 (IL-6) increase the risk of developing advanced periductal fibrosis (APF) and CCa by promoting CCa cell line proliferation. Anti-helminthic drugs can help decrease the risk of CCa caused by flukes. Surgical resection of the tumor and liver transplantation might be helpful too. Chemotherapy is considered for patients with advanced CCa when they cannot undergo surgery or when other treatment options fail to show improvement. Improvements in hygiene, health education, screening for fluke infection, and anti-helminthic therapy can help prevent liver fluke infection and thus the occurrence of CCa.