Early detection of liver fluke

Asian liver fluke infections, namely infection with the trematode helminths Opisthorchis viverrini, O. felineus and Clonorchis sinensis, are highly endemic in many areas in Asia and Eastern Europe. Deeply culturally rooted habits of raw and undercooked fish dishes consumption are the origin of the infection. Asian liver fluke infections are typically prevalent in rural, resource-poor settings with little access to quality health services. The presence of adult fluke worms in the bile ducts of the liver in combination with other socio-culturally, behavioural and geographically rooted risk factors such as nitrosamine rich diets, smoking, alcohol consumption, concomitant viral hepatitis infections and other factors determine the severity of developing liver morbidity. Chronic infection with liver fluke may induce a fatal bile duct cancer, cholangiocarcinoma (CCA). In most Asian liver fluke endemic settings, the true extent of liver fluke induced liver pathologies is unknown and underestimated, resulting in an inadequate allocation of resources for prevention and control. The lack of easily measurable disease markers are a fundamental problem. Also lacking are detailed risk pattern assessments for the liver diseases associated with the liver fluke infections. In Lao PDR, about half of the population is infected with O. viverrini.

Our project pursues the following objectives: (i) to assess the prevalence of different liver pathologies associated with O. viverrini infection in adults of endemic settings in central and southern Lao PDR; (ii) to identify factors associated with the presence of moderate (periductal fibrosis, PF+) and severe liver disease (advanced periductal fibrosis APF+) in O. viverrini-infected adults, placing particular emphasis on the history of praziquantel treatment; (iii) to assess the predictive capacity for the presence of O. viverrini induced PF+, APF+ and precancerous lesions of CCA in Lao PDR of known biomarkers and the latest potential candidates, namely, ES exosomes of O. viverrini (in serum) and 8-oxodG (in urine); (iv) to establish a biobank consisting of urine, serum and stool aliquots to agnostically identify new biomarkers for detecting the presence or predicting the development of O. viverrini induced severe liver disease.

The study will provide for the first time detailed information on the amount of liver morbidity linked with O. viverrini infection and present in the communities of Lao PDR. It will elucidate the risk pattern responsible for this severe morbidity development in addition to O. viverrini infection and therefore provide new mechanistic insights. In particular, it will show whether the history of repeated treatment with Praziquantel may result in a morbidity increase, which has direct implications for control of liver fluke infections in Lao PDR and other Asian liver fluke endemic settings and will inform treatment policy. Furthermore, our study will show the predictive capacity of new biomarkers. A biobank will lay the foundation for biomarker work which has a high potential to generate further disease risk and disease diagnostic markers in future. The study will clarify the public health dimension of O. viverrini in Lao PDR which help generate adequate resources to combat the disease. Finally, it will contribute to increase primary and secondary prevention of cancer in Lao PDR and other Southeast Asia.

• Lao People’s Democratic Republic (Lao PDR)

• Link to project on SNSF research database P3