Table 2.
Multivariable-adjusted HRs of CCA and HCC.
| Variable/Group | CCA Incidence a | HCC Incidence b | p-Value for Heterogeneity | ||||||
|---|---|---|---|---|---|---|---|---|---|
| No. of Cases | p | HR | (95% CI) | No. of Cases |
p | HR | (95% CI) | ||
| Age, years | |||||||||
| Per 10-year older | 1388 | <0.001 | 2.59 | (2.13–3.14) | 2920 | <0.001 | 1.62 | (1.42–1.85) | <0.001 |
| Sex, men (vs. women) | 945 | <0.001 | 1.91 | (1.66–2.19) | 2407 | <0.001 | 3.77 | (3.38–4.20) | <0.001 |
| Smoking status | |||||||||
| Never smoker | 794 | 1.00 | (Reference) | 1424 | 1.00 | (Reference) | |||
| Past smoker | 143 | 0.154 | 1.15 | (0.95–1.36) | 347 | 0.163 | 1.09 | (0.97–1.24) | 0.664 |
| Current smoker, <1 pack/day | 318 | <0.001 | 1.31 | (1.13–1.52) | 863 | <0.001 | 1.35 | (1.23–1.49) | 0.701 |
| ≥1 pack/day | 84 | 0.002 | 1.46 | (1.14–1.85) | 158 | 0.116 | 0.87 | (0.73–1.03) | 0.001 |
| Alcohol use, g ethanol/day | |||||||||
| None | 743 | 1.00 | (Reference) | 1387 | 1.00 | (Reference) | |||
| <10 | 222 | 0.257 | 0.91 | (0.78–1.07) | 542 | 0.002 | 0.84 | (0.76–0.94) | 0.430 |
| 10–39 | 277 | 0.032 | 1.19 | (1.01–1.39) | 632 | 0.402 | 0.96 | (0.86–1.06) | 0.025 |
| ≥40 | 120 | <0.001 | 1.54 | (1.25–1.89) | 284 | <0.001 | 1.40 | (1.22–1.60) | 0.460 |
| Per 140 g ethanol/week increase | 1388 | <0.001 | 1.12 | (1.06–1.17) | 2920 | <0.001 | 1.11 | (1.07–1.15) | 0.869 |
| Body mass index, kg/m 2 | |||||||||
| <18.5 | 35 | 0.173 | 0.79 | (0.56–1.11) | 73 | 0.975 | 1.00 | (0.79–1.26) | 0.270 |
| 18.5–24.9 | 847 | 1.00 | (Reference) | 1840 | 1.00 | (Reference) | |||
| 25–29.9 | 458 | 0.157 | 1.09 | (0.97–1.22) | 927 | 0.578 | 0.98 | (0.90–1.06) | 0.139 |
| ≥30 | 48 | 0.025 | 1.40 | (1.04–1.88) | 80 | 0.380 | 1.11 | (0.88–1.38) | 0.212 |
| Per 5 kg/m2 increase | 1388 | 0.006 | 1.13 | (1.04–1.23) | 2920 | 0.864 | 0.99 | (0.93–1.06) | 0.020 |
| Diabetes status (serum glucose, mg/dL) | |||||||||
| Normoglycemia (<100) | 796 | 1.00 | (Reference) | 1640 | 1.00 | (Reference) | |||
| IFG (101–125) | 341 | 0.412 | 1.05 | (0.93–1.20) | 693 | 0.010 | 1.13 | (1.03–1.23) | 0.417 |
| Diabetes (≥126 or known diabetes) | 251 | <0.001 | 1.36 | (1.18–1.57) | 587 | <0.001 | 1.83 | (1.66–2.01) | 0.001 |
| Per 18 mg/dL increase | 1388 | 0.013 | 1.05 | (1.01–1.09) | 2920 | <0.001 | 1.12 | (1.10–1.15) | 0.002 |
| Alanine aminotransferase (ALT), IU/L | |||||||||
| <20 | 481 | <0.001 | 0.79 | (0.71–0.90) | 299 | <0.001 | 0.35 | (0.30–0.40) | <0.001 |
| 20–39 | 691 | 1.00 | (Reference) | 1029 | 1.00 | (Reference) | |||
| 40–59 | 139 | 0.164 | 1.14 | (0.95–1.37) | 711 | <0.001 | 3.47 | (3.15–3.83) | <0.001 |
| 60–79 | 43 | 0.056 | 1.35 | (0.99–1.84) | 372 | <0.001 | 6.09 | (5.39–6.88) | <0.001 |
| ≥80 | 34 | 0.135 | 1.30 | (0.92–1.84) | 509 | <0.001 | 8.63 | (7.70–9.66) | <0.001 |
| Total cholesterol, mg/dL | |||||||||
| Per 39 mg/dL increase | 1388 | 0.001 | 0.91 | (0.87–0.97) | 2920 | <0.001 | 0.55 | (0.53–0.57) | <0.001 |
| Comorbid liver disease | |||||||||
| Hepatitis B virus infection | 14 | <0.001 | 2.71 | (1.60–4.59) | 287 | <0.001 | 11.80 | (10.27–13.57) | <0.001 |
| Hepatitis C virus infection | 3 | 0.369 | 1.89 | (0.47–7.63) | 57 | <0.001 | 7.99 | (6.11–10.44) | 0.047 |
| Liver cirrhosis | 4 | 0.619 | 1.29 | (0.48–3.45) | 255 | <0.001 | 19.38 | (16.71–22.47) | <0.001 |
| Alcoholic liver disease | 15 | 0.151 | 1.45 | (0.87–2.43) | 81 | <0.001 | 1.79 | (1.42–2.24) | 0.474 |
| Biliary tract disease | |||||||||
| Cholelithiasis (gallstone disease) | 18 | 0.004 | 2.94 | (1.40–6.17) | 13 | 0.131 | 1.53 | (0.88–2.64) | 0.164 |
| Choledocholithiasis (bile duct stone) | 11 | <0.001 | 13.73 | (7.58–24.88) | 2 | 0.692 | 1.32 | (0.33–5.30) | 0.002 |
Abbreviations: HR—hazard ratio; 95% CI—95% confidence interval; CCA—cholangiocarcinoma; HCC—hepatocellular carcinoma; IFG—impaired fasting glucose. a Adjustment for age, sex, smoking, alcohol consumption, physical activity, income, BMI, serum glucose, hepatitis B infection, and choledocholithiasis. b Adjustment for age, sex, smoking, alcohol consumption, physical activity, income, BMI, serum glucose, liver cirrhosis, hepatitis B virus, and hepatitis C infection.