Table 2.
Host and viral risk factors for post-sustained virologic response (SVR) hepatocellular carcinoma (HCC) development (summarized from multivariable Cox regression models)
| Risk factor | Variable | n | Country | Follow-up, median, years | Hazard ratio | 95% CI | P value | Reference | |
|---|---|---|---|---|---|---|---|---|---|
| Host factor | Fibrosis | ||||||||
| Pre-SVR | |||||||||
| Histological stage F2-4 | 562 | Japan | 4.8 | 10.7 | 2.2–192.1 | <0.001 | [53] | ||
| Histological stage, F3-4 | 1273 | Japan | 1.1 | 9.0 | 2.3–35.2 | 0.002 | [34] | ||
| Histological stage, F3-4 | 1094 | Japan | 4.2 | 3.2 | 1.6–7.2 | <0.001 | [58] | ||
| Histological stage, F3-4 | 376 | Taiwan | 7.6 | 12.8 | 1.6–101.9 | 0.021 | [56] | ||
| Histological stage, F3-4 | 871 | Taiwan | 3.4 | 4.0 | 1.5–10.7 | 0.007 | [51] | ||
| Platelet, < 150 × 103/mm3 | 1056 | Japan | 4.7 | 2.8 | 1.1–7.2 | 0.04 | [68] | ||
| Platelet, < 150 × 103/mm3 | 871 | Taiwan | 3.4 | 2.8 | 1.2–6.4 | 0.015 | [51] | ||
| Platelet, < 150 × 103/mm3 | 1000 | Europe and Canada | 5.7 | 1.1 | 1.0–1.1 | 0.029 | [61] | ||
| Albumin, < 35 g/dL | 399 | Sweden | 7.8 | 4.4 | 1.3–14.7 | 0.016 | [69] | ||
| Liver cirrhosis, yes | 1351 | Taiwan | 4.0 | 8.4 | 4.1–17.0 | <0.001 | [70] | ||
| Liver cirrhosis, yes | 4663 | Canada | 5.6 | 3.2 | 1.2–9.0 | – | [71] | ||
| Post-SVR | |||||||||
| FIB-4 index, high | 522 | Japan | 7.2 | 1.7 | 1.1–2.9 | 0.02 | [55] | ||
| APRI ≥ 0.7 | 1351 | Taiwan | 4.0 | 2.9 | 1.5–5.7 | 0.002 | [70] | ||
| Elastography liver stiffness > 12 kPa | 376 | Taiwan | 7.6 | 6.3 | 2.1–19.5 | 0.001 | [56] | ||
| Liver cirrhosis, yes | 10,738 | USA | 2.8 | 6.7 | 4.3–10.4 | <0.001 | [36] | ||
| Platelet, < 130 × 103/mm3 | 571 | Japan | 9.0 | 3.9 | 1.5–10.1 | 0.004 | [72] | ||
| Age, years | ≥50 | 562 | Japan | 4.8 | 4.1 | 1.4–17.4 | <0.01 | [53] | |
| ≥55 | 571 | Japan | 9.0 | 3.6 | 1.4–9.6 | 0.009 | [72] | ||
| ≥60 | 642 | Taiwan | 4.4 | 3.7 | 1.3–10.2 | 0.012 | [52] | ||
| ≥60 | 871 | Taiwan | 3.4 | 3.8 | 1.7–8.4 | 0.001 | [51] | ||
| ≥60 | 4663 | Canada | 5.6 | 4.4 | 1.3–15.3 | – | [71] | ||
| >60 | 1094 | Japan | 4.2 | 3.1 | 1.3–6.6 | 0.009 | [58] | ||
| >60 | 1056 | Japan | 4.7 | 3.1 | 1.3–7.4 | 0.01 | [68] | ||
| >60 | 1000 | Europe and Canada | 5.7 | 9.8 | 1.2–77.8 | 0.031 | [61] | ||
| ≥65 | 1425 | Japan | 3.3 | 5.8 | 1.1–30.1 | 0.036 | [54] | ||
| ≥65 | 1351 | Taiwan | 4.0 | 2.7 | 1.2–6.3 | 0.017 | [70] | ||
| ≥65 | 10,738 | USA | 2.8 | 4.5 | 2.0–10.4 | <0.001 | [36] | ||
| Older | 589 | Taiwan | 4.7 | 1.1 | 1.0–1.1 | 0.046 | [73] | ||
| Sex | Male | 1094 | Japan | 4.2 | 12.0 | 2.8–50.0 | <0.001 | [58] | |
| Male | 4663 | Canada | 5.6 | 3.3 | 1.1–9.6 | – | [71] | ||
| Male | 571 | Japan | 9.0 | 7.6 | 1.7–33.1 | 0.007 | [72] | ||
| Diabetes | Yes | 522 | Japan | 7.2 | 2.1 | 1.1–4.0 | 0.045 | [55] | |
| Yes | 376 | Taiwan | 7.6 | 4.0 | 1.3–12.1 | 0.021 | [56] | ||
| Yes | 399 | Sweden | 7.8 | 3.2 | 1.1–9.6 | 0.035 | [69] | ||
| Yes | 10,738 | USA | 2.8 | 1.9 | 1.2–2.9 | 0.005 | [36] | ||
| Yes | 1000 | Europe and Canada | 5.7 | 2.3 | 1.0–5.3 | 0.057 | [61] | ||
| Yes | 4663 | Canada | 5.6 | 1.6 | 0.6–4.0 | – | [71] | ||
| Yes | 589 | Taiwan | 4.7 | 3.8 | 1.4–10.1 | 0.008 | [73] | ||
| Elixhauser comorbidity index | Yes (≥1) | 4663 | Canada | 5.6 | 2.2 | 1.0–5.1 | – | [71] | |
| Alpha-fetoprotein, ng/mL | |||||||||
| Pre-SVR | ≥8 | 562 | Japan | 4.8 | 2.6 | 1.2–6.1 | <0.05 | [53] | |
| ≥15 | 1351 | Taiwan | 4.0 | 1.9 | 1.0–3.6 | 0.038 | [70] | ||
| ≥20 | 871 | Taiwan | 3.4 | 3.2 | 1.6–6.2 | 0.001 | [51] | ||
| Post-SVR | ≥5 | 1425 | Japan | 3.3 | 8.1 | 2.7–23.9 | <0.001 | [54] | |
| ≥5 | 571 | Japan | 9.0 | 3.6 | 1.4–9.6 | 0.009 | [72] | ||
| ≥15 | 1351 | Taiwan | 4.0 | 2.3 | 1.0–5.3 | 0.043 | [70] | ||
| ≥10 | 1094 | Japan | 4.2 | 7.8 | 2.9–16.8 | <0.001 | [58] | ||
| Race/ethnicity | Hispanic | 10,738 | USA | 2.8 | 2.3 | 1.1–4.8 | 0.032 | [36] | |
| Alcohol abuse | Yes | 562 | Japan | 4.8 | 3.9 | 1.7–9.0 | <0.01 | [53] | |
| Yes | 10,738 | USA | 2.8 | 1.7 | 1.1–2.6 | 0.021 | [36] | ||
| Yes | 4663 | Canada | 5.6 | 1.1 | 0.34–3.3 | – | [71] | ||
| Illicit drug use | Yes | 4663 | Canada | 5.6 | 3.7 | 1.0–14.3 | – | [71] | |
| AST | >100 IU/L | 1056 | Japan | 4.7 | 3.1 | 1.3–7.3 | 0.01 | [68] | |
| AST/ALT ratio | >0.72 | 1000 | Europe and Canada | 5.7 | 1.0 | 1.0–1.1 | 0.068 | [61] | |
| GGT | >75 U/L | 642 | Taiwan | 4.4 | 6.4 | 2.2–18.9 | 0.001 | [52] | |
| Viral factor | Genotype 1b with Gln70 (His70) variant | 1273 | Japan | 1.1 | 10.5 | 2.9–38.2 | <0.001 | [34] | |
| Genotype 3 | 10,738 | USA | 2.8 | 1.6 | 1.0–2.7 | 0.071 | [36] | ||
| Genotype 3 | 4663 | Canada | 5.6 | 1.4 | 0.58–3.4 | – | [71] |
All data are from interferon-based studies
APRI aspartate aminotransferase-to-platelet ratio index, ALT alanine aminotransferase, AST aspartate aminotransferase, FIB-4 fibrosis-4, GGT gamma-glutamyl transpeptidase, HCV hepatitis C virus, HCC hepatocellular carcinoma, SVR sustained virologic response