Following adjustment for covariates, only three cancer biomarkers, CYFRA 21-1, SCF and OPN, were positively associated with ICC in patients with LD or NLD microbiota, whereas eleven cancer biomarkers, IL-6, TNFα, TRAIL, sFas, sFasL, FGF2, HGF, VEGF, prolactin, leptin, and AFP were positively associated with ICC only in patients with NLD microbiota when compared to Ctrl HPV−. The gene discussed is LEP; the disease is intrahepatic cholangiocarcinoma.