Trial Information

Pathogenesis of Liver Fluke Induced Cancer in Thailand

Liver fluke infection caused by Opisthorchis viverrini (OV) is a major public health problem
in parts of East Asia. In Thailand, an estimated 6 million are people infected with OV.
Experimental and epidemiological evidence strongly implicate OV infection in the etiology of
cholangiocarcinoma (CCA). Studies have shown 10-20% of OV-infected persons have advanced
periportal fibrosis (HBA) that progresses to CCA. OV infection may cause inflammation of the
bile ducts that results in DNA damage of the epithelium and subsequent malignant
transformation. The primary objective of this study is to determine if in-vitro levels of
inflammatory cytokines induced by crude antigen extracts of OV are associated with the
hepatobiliary abnormalities known to progress to CCA in OV-infected adults aged 20 to 60
years of age. The secondary objective is to determine if in-vitro levels of inflammatory
cytokines induced by crude antigen extracts of OV in adults with hepatobiliary abnormalities
change 12 months after treatment with praziquantel and if these changes are associated with
persistent advanced fibrosis (grade 2 or 3) as determined by ultrasonography. The primary
outcome measure is elevated levels of inflammatory cytokines (such as TNF-alpha) induced by
OV infection are associated with a 50% greater risk (OR = 1.50) of having advanced fibrosis
(grade 2 or 3) as determined by ultrasonography. The secondary outcome measure is elevated
levels of inflammatory cytokines 12 months after treatment for OV infection are associated
with a 50% greater risk (OR = 1.50) of maintaining the advanced fibrosis that is known to
progress to CCA over this time period. District health outposts reporting greater than or
equal to 20 percent prevalence of OV infection among adults will be identified, whereupon
males and females, 20 to 60 years of age, will be screened for OV infection. Study sites in
Thailand will be districts of Ban Pai, Chonnabot, Muncha Khiri and Kok Pochai, regions along
the drainage of the Chi River, in the vicinity of the regional capitol, Khon Kaen city. A
recruitment ceiling of 20,000 individuals will be established to screen for infection with
OV, with 6,000 enrolled in the observational and longitudinal parts of the study.
OV-infected individuals will receive an ultrasound examination that will be graded as either
HBA positive (advanced fibrosis) or HBA negative (non-advanced fibrosis). Over a 24 month
period, 1,116 OV-infected individuals who are HBA positive will be recruited. The first 484
OV-infected individuals with HBA will be age and sex matched with OV-infected individuals
from the same region who are HBA negative. Blood samples will be drawn from all volunteers
and used in immunological evaluations of OV infection in relation to HBA status. This will
constitute the observation stage of the study. The 1,116 OV-infected individuals with HBA
will be followed for an additional 12 months, with an ultrasound exam and a blood draw. This
will constitute the longitudinal stage of the study. All volunteers will then be treated for
OV infection with praziquantel.