Table 1.
Risk factors for CCA. Established, emerging, and controversial risk factors for CCA.
| Factor | Type of Study | Calculated Risk |
|---|---|---|
| PSC | Population-based study | OR 22 for iCCA, OR 41 for eCCA |
| Bile duct cysts | Meta-analysis | OR 26.71 for iCCA, OR 34.94 for eCCA |
| Caroli’s disease | Population-based study | OR 38 for iCCA, OR 97 for eCCA |
| Hepatolithiasis | Population-based study | 69% of the patients who underwent surgery for CCA had hepatolithiasis |
| Choledocholithiasis | Meta-analysis | OR 10.08 for iCCA, OR 18.58 for eCCA |
| Chronic hepatitis C | Meta-analysis | OR 4.28 for iCCA, OR 1.98 for eCCA |
| Chronic hepatitis B | Meta-analysis | OR 4.57 for iCCA, OR 2.11 for eCCA |
| Cirrhosis | Meta-analysis | OR 15.32 for iCCA, OR 3.82 for eCCA |
| MAFLD and NASH | Meta-analysis | OR 2.2 for iCCA, OR 1.5 for eCCA |
| Hemochromatosis | Population-based study | OR 2.1 for iCCA |
| Liver fluke (Opisthorchis Viverrini, Clonorchis Sinensis) | Meta-analysis | OR 5 iCCA > eCCA |
| Genetic factors | GWAS | IDH, EPHA2, BAP1 mutations, and FGFR2 fusions are more common in iCCA, and PRKACA and PRKACB fusions are more common in eCCA. Epigenetic hypermethylation of CpG early appears in CCA carcinogenesis. |
| Diabetes | Meta-analysis | OR 1.73 for iCCA, OR 1.5 for eCCA |
| Obesity | Meta-analysis | OR 1.14 for iCCA, OR 1.2 for eCCA |
| Hypertension | Meta-analysis | OR 1.10 for iCCA, OR 1.21 for eCCA |
| Alcohol consumption | Meta-analysis | OR 3.15 for iCCA, OR 1.75 for eCCA |
| Smoking | Meta-analysis | OR 1.25 for iCCA, OR 1.69 for eCCA |
| Races | Population-based study | Hispanics and Asian/Pacific Islanders are more likely to have CCA compared with Caucasians, and African American race is inversely associated with CCA |
| Asbestos | Case-control study | OR 4.8 for iCCA, OR 2.1 for eCCA |
| Case-control study | OR 1.1–1.7 for iCCA, no association with eCCA | |
| Thorotrast | Retrospective study | RR > 300 |