Study outcome and independent variables

The primary outcome for this study was CCA which was defined as histologically positive diagnosis and categorized into two groups (no/yes). CCA was diagnosed through US, CT/MRI, and histopathological examination. Positive US results were defined as those indicating liver mass and/or bile duct dilatation, so-called suspected CCA. Those included in this group were referred to receive either CT or MRI scans. For the results of CT/MRI, there were only two categories—positive or negative for CCA. Biopsy confirmation for positive CCA was then needed. Participants who did not have suspicious US nor CT/MRI results were classified as negative for CCA. Each US examination was performed by either radiologists or well-trained general practitioners and was verified centrally by a radiologist at a tertiary hospital. The CT/MRI was mainly done by radiologists at tertiary hospitals. The data of histological findings were based on the standard protocol of the tertiary hospital at Khon Kaen University, Thailand.

The independent variables include the combinations of lifetime history of O. viverrini infection and diagnosis of DM. These were categorized into four groups, namely, uninfected with O. viverrini and being non-DM (OV- & DM-), uninfected with O. viverrini and having DM (OV- & DM+), infected with O. viverrini and being non-DM (OV+ & DM-), and infected with O. viverrini and having DM (OV+ & DM+). The co-variates include gender, age at enrollment, highest achieved educational level, occupation, history of smoking cigarettes defined as no/yes (current orever), drinking alcohol defined as no/yes (current or previous), history of eating raw fish defined as no/yes (current or previous), and history of praziquantel treatments (PZQ) defined as never/once/twice/three times or more. PZQ is used to treat O. viverrini infections. The level factors comprise individual, and province factors.