Pathogenesis of Liver Fluke Induced Cancer in Thailand
Condition: Opisthorchis Viverrini
Study type: Observational

Summary: 
      Opisthorchis viverrini (OV) is a parasite that individuals get from eating raw fish.
      Infections with this parasite have been associated with liver abnormalities that sometimes
      lead to bile duct cancer. The purpose of this study is to find out how many people in several
      areas of the Khon Kaen province are infected with OV, what affect this parasite has on the
      liver, how the immune system reacts to infection with this parasite, and how the liver is 12
      months after being treated for this parasite. Study participants will include 6,000
      volunteers, ages 20-60, living in villages surrounding Khon Kaen that have large numbers of
      people infected with OV. Study procedures will include a stool sample, an ultrasound (sound
      waves bounced off internal organs to create a picture), and a blood sample. Individuals found
      to test positive for the parasite will be treated at their local primary health care unit.
      Participants will be involved in study procedures for up to 12 months.
    

Detailed description: 
      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.
    

Time perspective: Prospective
Keywords: Opisthorchis viverrini, liver fluke, Thailand, cancer