Liver flukes: the malady neglected

Abstract

Liver fluke disease is a chronic parasitic inflammatory disease of the bile ducts. Infection occurs through ingestion of fluke-infested, fresh-water raw fish. The most well-known species that cause human infection are Clonorchis sinensis, Opisthorchis viverrini and Opisthorchis felineus. Adult flukes settle in the small intrahepatic bile ducts and then they live there for 20-30 years. The long-lived flukes cause long-lasting chronic inflammation of the bile ducts and this produces epithelial hyperplasia, periductal fibrosis and bile duct dilatation. The vast majority of patients are asymptomatic, but the patients with heavy infection suffer from lassitude and nonspecific abdominal complaints. The complications are stone formation, recurrent pyogenic cholangitis and cholangiocarcinoma. Approximately 35 million people are infected with liver flukes throughout the world and the exceptionally high incidence of cholangiocarcinoma in some endemic areas is closely related with a high prevalence of liver fluke infection. Considering the impact of this food-borne malady on public health and the severe possible clinical consequences, liver fluke infection should not be forgotten or neglected.

Keywords: Cholangiocarcinoma; Cholangiocarinogenesis; Clonorchiasis; Foodborne parasite; Liver flukes; Opisthorchiasis.

Fig. 1

Adult Clonorchis sinensis within intrahepatic bile duct. Endoscopy reveals "rayfish-like" or "leech-like" flat worm moving within lumen, and it has whitish-yellow ventral sucker at tapered head portion of worm. Note reddish inner surface of bile duct at background as mark of blood sucking (Courtesy of Dong Wan Seo, MD, Asan Medical Center, Seoul, Korea).

Fig. 2

Photomicrograph of rabbit bile duct that was experimentally infected with C. sinensis, and it shows adult fluke in bile duct. Note extensive epithelial hyperplasia of mucosa around fluke and periductal fibrosis (arrows) (Hematoxylin & Eosin staining, × 40).

Fig. 3

70-year-old man with clonorchiasis and he complained of lassitude. He had been previously admitted 10 years ago because of jaundice and he was diagnosed with clonorchiasis and treated with praziquantel. Five years later, he had cholecystectomy for gallbladder stones and cholecystitis. Since then, he has been suffering from general weakness and lassitude. He has been eating raw fresh-water fish frequently for more than 12 years because he believed raw fish was helpful for his health. CT shows mild dilatation of small intrahepatic bile ducts up to periphery of liver without dilatation of large bile ducts, which is characteristic for clonorchiasis.

Fig. 4

Photomicrograph of C. sinensis eggs (arrows) in calcium-bilirubinate stone (Hematoxylin & Eosin staining, × 400). (Reprinted from AJR Am J Roentgenol 1991;157:1-8)

Fig. 5

63-year-old man with clonorchiasis and intrahepatic bile duct stones. A. MR cholangiogram shows severe dilatation of posterior inferior segmental branch of right hepatic lobe and it is filled with multiple stones. There is no definite intraductal mass. Note mild dilatation of the other segmental bile ducts. B-D. Microphotographs show several adult C. sinensis (B), bile duct stone (arrow in C) and low-grade biliary intraepithelial neoplasia (D) (B-D; Hematoxylin & Eosin staining, × 200). Note micropapillary growth of atypical biliary epithelium (arrows in D). Biliary intraepithelial neoplasia is microscopic structure and this is not visible macroscopically or on radiological images.

Fig. 6

Cholangiocarcinoma that was incidentally found in patient with opisthorchiasis. Transverse sonogram of middle age man who was included in sonographic survey in village near Vientiane, Laos shows 3.0 cm mass (arrows) associated with dilatation of bile ducts peripheral to mass (arrowheads). CT image of same patient showed mass, which was consistent with cholangiocarcinoma (not shown).

Fig. 7

Intraductal papillary adenocarcinoma that developed during three years of follow-up in patient with clonorchiasis. A. CT shows mild dilatation of intrahepatic duct (arrows). B. CT image three year later shows focal dilatation of segmental bile duct, which is filled with small, soft tissue mass (arrow). C. Microphotograph shows focally invasive tubular adenocarcinoma that developed from papillary adenoma within lumen of bile duct (arrows). Intraductal papillary neoplasm is sizable and it is visible macroscopically and radiologically (scanning power view, × 1).

Fig. 8

Cholangiocarcinoma at common hepatic duct in 72-year-old man with severe clonorchiasis. A. CT shows mass at bifurcation of right and left hepatic ducts (arrow) and severe dilatation of entire intrahepatic duct up to surface of liver. B. MR cholangiogram shows defect at common hepatic duct (arrows), which represents cholangiocarcinoma. C. Microphotograph from common hepatic duct (adjacent to main tumor) shows high grade biliary intraepithelial neoplasia, which is precursor of cholangiocarcinoma (Hematoxylin & Eosin staining, × 200). D. Microphotograph from common hepatic duct (adjacent to main tumor) shows intraductal tubular adenocarcinoma and goblet cell hyperplasia (arrows) (Hematoxylin & Eosin staining, × 200). E. Microphotograph from common hepatic duct (main tumor) shows adenosquamous carcinoma (Hematoxylin & Eosin staining, × 100).