Liver Fluke Induces Cholangiocarcinoma

Liver fl uke infection caused by Opisthorchis viverrini, O. felineus, and Clonorchis sinensis is a major public health problem in East Asia and Eastern Europe. Currently, more than 600 million people are at risk of infection with these trematodes [1]. O. viverrini is endemic in Southeast Asian countries, including Thailand, Lao People’s Democratic Republic, Vietnam, and Cambodia [2], and C. sinensis infection is common in rural areas of Korea and China. Opisthorchiasis has been extensively studied in Thailand, where an estimated 6 million people are infected with the liver fl uke (calculated from overall 9.4% prevalence within the population in 2001) [3]. Infection with these food-borne parasites is prevalent in areas where uncooked cyprinoid fi sh are a staple of the diet. Due to poor sanitation practices and inadequate sewerage infrastructure, people infected with O. viverrini and C. sinensis pass parasite eggs in their faeces into natural water reservoirs, where the parasite eggs are eaten by intermediate host snails, for example, aquatic snails of the genus Bithynia, the fi rst intermediate host of O. viverrini. After hatching, free swimming parasites, called cercariae, are released from the infected snails. Cercariae then locate their next intermediate host, cyprinoid fi shes, encyst in the fi ns, skin, and muscles of the fi sh, and become metacercariae. The metacercariae are infective to humans and other fi sh-eating mammals upon ingestion of raw or undercooked fi sh in dishes such as koi-pla (Figure 1), and in turn the parasite’s life cycle is completed (Figure 2). Most people with opisthorchiasis or clonorchiasis have no symptoms. Only 5%–10% of infected people, in general those with heavy fl uke infections, have non-specifi c symptoms such as right upper quadrant abdominal pain, fl atulence, and fatigue [4,5]. Enlargement of the gall bladder can be detected by ultrasonography, and is reversed after elimination of fl ukes by praziquantel [6]. Nonetheless, heavy, long-standing infection is associated with a number of hepatobiliary diseases, including cholangitis, obstructive jaundice, hepatomegaly, fi brosis of the periportal system, cholecystitis, and cholelithiasis [7–10]. Moreover, both experimental and epidemiologic evidence strongly implicates liver fl uke infection in the aetiology of one of the liver cancer subtypes—cholangiocarcinoma (CCA), or cancer of the bile ducts [2,11]. The pathology of clonorchiasis was recently reviewed in detail by Rim [12]. Unlike O. viverrini, C. sinensis is not considered a Group I carcinogen (known to be carcinogenic in humans) [2], despite its widespread prevalence [13]. In Liver Fluke Induces Cholangiocarcinoma Banchob Sripa, Sasithorn Kaewkes, Paiboon Sithithaworn, Eimorn Mairiang, Thewarach Laha, Michael Smout,