Chronic
opisthorchiasis caused by
Opisthorchis viverrini infection is characterized by advanced periductal
fibrosis leading to
hepatobiliary diseases (HBD), including
cholangiocarcinoma (CCA). We aimed to determine fibrotic markers to differentiate HBD status including
opisthorchiasis, benign biliary disease (BBD) and CCA. Candidate fibrotic markers in plasma of healthy individuals (n = 14) and patients with
opisthorchiasis (n = 32, pre- and post-treatment with
praziquantel), BBD (n = 31), CCA (n = 37) and other types of
tumors (n = 14) were measured by ELISA and zymography. Plasma levels of
hydroxyproline (HYP),
collagen I, MMP-7 and TIMP2 in
opisthorchiasis patients were significantly higher than those in healthy individuals, and MMP9/TIMP2 balance may be associated with tissue resorption after
praziquantel treatment. HYP and
TIMP-2 levels were significantly correlated with periductal
fibrosis status evaluated by ultrasonography. Plasma HYP level of CCA patients was the highest among HBD patients (p < 0.05). ROC curves revealed HYP, MMP-7 and
collagen I levels significantly distinguished
opisthorchiasis, BBD and CCA (p < 0.001). Odd ratio (OR) analysis demonstrated these markers in
opisthorchiasis were predictable for BBD risk (p < 0.05; OR = 28.50, 10.12 and 4.63 for
collagen I,
MMP-7 and HYP, respectively), and the risk was reduced by
praziquantel treatment. Interestingly, only plasma HYP level in BBD was predictable for CCA risk (OR = 3.69; p = 0.020). In conclusion, plasma HYP,
collagen I and MMP-7 may be useful as novel predictive markers of
opisthorchiasis-related BBD, and HYP may be used as a diagnostic marker for CCA.