Background
Effect of HCV cure on HCC development
Author (year), Reference | Major race | Country | Type of anti-HCV therapy | n | Follow-up, median, years | Male sex, n (%) | Age, median, years | Advanced fibrosis/cirrhosis, n (%) | Treatment for previous HCC | Reported HCC incidence in SVR, % (interval in years) | Annual HCC incidence in SVR, % | Reported HCC incidence in non-SVR, % (interval in years) | Annual HCC incidence in non-SVR, % | Study design |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
HCC development | ||||||||||||||
Akuta (2011) [34] | Asian | Japan | IFN-based | 1273 | 1.1 | 783 (61.5) | 53 | 109 (8.6) | – | 3.2 (5) | 0.65 | – | – | Retrospective |
Chang (2012) [51] | Asian | Taiwan | IFN-based | 1271 (including 400 non-SVR) | 3.4 | 661 (75.9) | 55.4a
| 355 (27.9) | – | 1.2 (3) | 0.4 | – | – | Retrospective |
Huang (2014) [52] | Asian | Taiwan | IFN-based | 642 | 4.4 | 302 (54.3) | 51.4a
| 86 (13.4) | – | 5.8 (5) | 1.2 | – | – | Retrospective |
Yamashita (2014) [53] | Asian | Japan | IFN-based | 562 | 4.8 | 311 (55.3) | 57 | 129 (23.0) | – | 3.1 (5) | 0.63 | – | – | Retrospective |
Oze (2014) [54] | Asian | Japan | IFN-based | 1425 | 3.3 | 727 (51.0) | 54.5 | 118 (11.6) | – | 2.6 (5) | 0.53 | 11.7 (5) | 2.49 | Prospective |
Toyoda (2015) [55] | Asian | Japan | IFN-based | 522 | 7.2 | 292 (55.9) | 50.6 | 27 (5.5) | – | 1.2 (5) | 0.24 | – | – | Retrospective |
Wang (2016) [56] | Asian | Taiwan | IFN-based | 376 | 7.6 | 185 (49.2) | 54.1 | 127 (33.8) | – | 1.4 (5) | 0.28 | – | – | Retrospective |
Kobayashi (2016) [57] | Asian | Japan | IFN-based | 528 | 7.3 | 308 (58.4) | 54 | 78 (14.8) | – | 2.2 (5) | 0.44 | – | – | Retrospective |
El-Serag (2016) [36] | Caucasian | USA | IFN-based | 10,738 | 2.8 | 10,232 (95.3) | 53.1a
| 1548 (14.4) | – | 0.33 (5) | 0.07 | – | – | Retrospective |
Nagaoki (2016) [58] | Asian | Japan | IFN-based | 1094 | 4.2 | 585 (53.5) | 60 | 208 (1.9) | – | 4.0 (5) | 0.82 | – | – | Retrospective |
Tada (2016) [59] | Asian | Japan | IFN-based | 587 | 14.0 | 324 (55.2) | 50 | – | – | 4.4 (10) | 0.45 | 14.7 (10) | 1.59 | Retrospective |
Tada (2016) [60] | Asian | Japan | IFN-based | 170 | 14.2 | 106 (62.4) | 52.5 | – | – | 7.1 (10) | 0.74 | – | – | Retrospective |
van der Meer (2016) [61] | Caucasian | Europe and Canada | IFN-based | 1000 | 5.7 | 676 (68.0) | 52.7 | 842 (85.0) | – | 7.6 (8) | 0.99 | – | – | Retrospective |
Kobayashi (2016) [57] | Asian | Japan | DAAs | 77 | 4.0 | 34 (44.2) | 63 | 23 (29.9) | – | 3.0 (5) | 0.62 | – | – | Retrospective |
HCC development or recurrence | ||||||||||||||
Conti (2016) [39] | Caucasian | Italy | DAAs | 344 (59 had previous HCC, including 30 non-SVR) | 0.5 | 207 (60.1) | 63 | 39 (11.3) | Resection, ablation, TACE | 3.2 (0.5)d
| 6.3d
| – | – | Retrospective |
Cheung (2016) [24] | Caucasian | UK | DAAs | 317 (18 had previous HCC) | 1.3 | NA | 54 | 254 (80.1) | Resection, ablation, TACE | 5.4 (1.3) | 4.27 | 11.2 (1.3) | 9.14 | Prospective |
HCC recurrence | ||||||||||||||
Saito (2014) [62] | Asian | Japan | IFN-based | 14 | 3.9 | 13 (92.9%) | 72 | 12 (85.7) | Resection, ablation | 18.0 (3) | 6.62 | 75.3 (3) | 46.61 | Retrospective |
Huang (2015) [63] | Asian | Taiwan | IFN-based | 56 | 4.4 | 36 (64.3) | 61.6 | 21 (37.5) | Resection, ablation | 43.2b
| – | 84.8b
| – | Retrospective |
Kunimoto (2016) [64] | Asian | Japan | IFN-based | 40 | 5.1 | 35 (87.5%) | 65 | 14 (35.0) | Resection, ablation | 23.0 (3) | 8.71 | 56.0 (3) | 27.37 | Retrospective |
Petta (2016) [65] | Caucasian | Italy | IFN-based | 57 | 2.8 | 41 (72.0) | 62 | 0 | Resection, ablation | 15.2 (2) | 8.24 | – | – | Retrospective |
Minami (2016) [66] | Asian | Japan | IFN-based | 38 | – | 27 (71.0) | 66 | 0 | Ablation | 52.9 (2) | 37.6 | – | – | Retrospective |
Conti (2016) [39] | Caucasian | Italy | DAAs | 59 (including 6 non-SVR) | 0.5 | 40 (67.8) | 72 | 10 (16.9) | Resection, ablation, TACE | 28.8d (0.5) | 49.3d
| – | – | Retrospective |
Reig (2016) [40] | Caucasian | Spain | DAAs | 58 | 0.5 | 40 (69.0) | 66.3 | 5 (8.6) | Resection, ablation, TACE | 27.6d (0.5) | 47.6d
| – | – | Retrospective |
ANRS study group (2016) [42] | Caucasian | France | DAAs | 189 (including 41 non-SVR) | 2.2 | 147 (78.0) | 62a
| 152 (80.0) | Resection, ablation, LT | 0.73b,d
| 8.76c,d
| 0.66b,e
| 7.92c,e
| Prospective |
ANRS study group (2016) [42] | Caucasian | France | DAAs | 13 | 1.8 | 11 (85.0) | 61a
| 13 (100) | Resection, ablation | 1.1b
| 13.3c
| 1.7b,e
| 20.76c,e
| Prospective |
ANRS study group (2016) [42] | Caucasian | France | DAAs | 314 | – | 257 (82.0) | 61a
| 49 (15.6) | LT | 2.2 (0.5) | 4.4 | – | – | Prospective |
Petta (2016) [65] | Caucasian | Italy | DAAs | 58 | 1.5 | 40 (69.0) | 66.3 | 2 (4.0) | Resection, ablation | 26.3 (2) | 15.3 | – | – | Retrospective |
Minami (2016) [66] | Asian | Japan | DAAs | 27 | – | 18 (67.0) | 71 | 0 | Ablation | 29.8 (2) | 17.7 | – | – | Retrospective |
Projected trend of HCV HCC incidence with new generation anti-HCV therapies
Post-SVR HCC risk factors
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] |