Background
Methods
Patients
Follow-up and postoperative treatments
Statistical analysis
Results
Patient characteristics
Features | Discovery cohort (n = 1540) | Validation Cohort (n = 630) |
---|---|---|
Age, median (range), year | 53.0 (10–86) | 53.0 (12–92) |
Gender, male/female | 1305 (84.7%)/235 (15.3%) | 530 (84.1%)/100 (15.9%) |
α-Fetoprotein (>200/≤200 ng/dL) | 593 (38.5%)/947 (61.5%) | 259 (41.1%)/371 (58.9%) |
Liver cirrhosis, yes/no/unknown | 1268 (82.3%)/251 (16.3%)/21 (1.4%) | 512 (81.3%)/102 (16.2%)/16 (2.5%) |
Hepatitis B history, yes/no/unknown | 1255 (81.5%)/254 (16.5%)/31 (2.0%) | 527 (83.7%)/94 (14.9%)/9 (1.4%) |
Tumor size, mean ± SD, cm | 5.3 ± 3.5 | 5.5 ± 3.7 |
Tumor number, multiple/solitary | 199 (12.9%)/1341 (87.1%) | 78 (12.4%)/552 (87.6%) |
Types of resection, anatomic/non-anatomic | 1222 (79.4%)/318 (20.6%) | 475 (75.4%)/155 (24.6%) |
Encapsulation, complete/none/unknown | 733 (47.6%)/803 (52.1%)/4 (0.3%) | 294 (46.7%)/335 (53.2%)/1 (0.2%) |
Tumor differentiation, I–II/III–IV/unknown | 1098 (71.3%)/421 (27.3%)/21 (1.4%) | 441 (70.0%)/171 (27.1%)/18 (2.9%) |
Microvascular invasion, yes/no | 389 (25.3%)/1151 (74.7%) | 205 (32.5%)/425 (67.5%) |
BCLC stage, 0/A/B | 194 (12.6%)/1192 (77.4%)/154 (10.0%) | 87 (13.8%)/484 (76.8%)/59 (9.4%) |
Correlations between MVI and clinical characteristics
Variables | Microvessel invasion | ||
---|---|---|---|
Yes (n = 389) | No (n = 1151) |
P
| |
Age, year | 52.1 ± 11.6 | 53.3 ± 11.7 | 0.082 |
Gender, male/female | 332 (85.3%)/57 (14.7%) | 973 (84.5%)/178 (15.5%) | 0.700 |
Hepatitis B history, yes/no | 317 (83.6%)/62 (16.4%) | 938 (83.0%)/192 (17.0%) | 0.776 |
ALT, U/L | 54.4 ± 84.7 | 50.7 ± 64.6 | 0.370 |
γ-GT, U/L | 94.3 ± 84.9 | 86.9 ± 92.7 | 0.168 |
Albumin, g/L | 40.9 ± 4.9 | 41.6 ± 4.6 | 0.010 |
Liver cirrhosis, yes/no | 312 (81.0%)/73 (19.0%) | 956 (84.3%)/178 (15.7%) | 0.153 |
α-Fetoprotein (>200/≤200 ng/dL) | 191 (49.1%)/198 (50.9%) | 402 (34.9%)/749 (65.1%) | <0.001 |
Tumor size, cm | 6.5 ± 3.8 | 4.9 ± 3.3 | <0.001 |
Tumor size (>5 cm/≤5 cm) | 195 (50.1%)/194 (49.9%) | 370 (32.1%)/781 (67.9%) | <0.001 |
Tumor number, solitary/multiple | 332 (85.3%)/57 (14.7%) | 1009 (87.7%)/142 (12.3%) | 0.239 |
Tumor encapsulation, complete/no | 166 (42.9%)/221 (57.1%) | 637 (55.4%)/512 (44.6%) | <0.001 |
Tumor differentiation, I–II/III–IV | 232 (59.9%)/155 (40.1%) | 866 (76.5%)/266 (23.5%) | <0.001 |
BCLC stage, 0/A/B | 24 (6.2%)/312 (80.2%)/53 (13.6%) | 170 (14.8%)/880 (76.5%)/101 (8.8%) | <0.001* |
Prognostic factors
Features | Overall survival | Recurrence-free survival | ||||||
---|---|---|---|---|---|---|---|---|
Univariate
P
| Multivariate | Univariate
P
| Multivariate | |||||
HR | 95% CI |
P
| HR | 95% CI |
P
| |||
Age, ≤52 vs. >52 year | 0.366 | NA | 0.457 | NA | ||||
Gender, female vs. male | 0.184 | NA | 0.958 | NA | ||||
Hepatitis B history, yes vs. no | 0.079 | NA | 0.124 | NA | ||||
Liver cirrhosis, yes vs. no | 0.010 | 1.493 | 1.152–1.937 | 0.002 | 0.057 | NA | ||
α-Fetoprotein, >200 vs. ≤200 ng/dL | <0.001 | 1.559 | 1.313–1.851 | <0.001 | <0.001 | 1.436 | 1.227–1.681 | <0.001 |
ALT, >75 vs. ≤75 U/L | 0.841 | NA | 0.313 | NA | ||||
γ-GT, >50 vs. ≤50 U/L | <0.001 | 1.420 | 1.176–1.715 | 0.002 | <0.001 | 1.331 | 1.125–1.575 | 0.001 |
Albumin, >35 vs. ≤35 g/L | <0.001 | 0.645 | 0.501–0.832 | 0.001 | 0.003 | 0.724 | 0.567–0.926 | 0.010 |
Tumor size, >5 vs. ≤5 cm | <0.001 | 2.052 | 1.715–2.455 | <0.001 | <0.001 | 1.724 | 1.464–2.029 | <0.001 |
Tumor number, solitary vs. multiple | <0.001 | 0.683 | 0.544–0.857 | 0.001 | <0.001 | 0.666 | 0.540–0.822 | <0.001 |
Tumor differentiation, III–IV vs. I–II | <0.001 | 1.275 | 1.065–1.528 | 0.008 | <0.001 | 1.290 | 1.091–1.525 | 0.003 |
Tumor encapsulation, complete vs. none | <0.001 | 1.312 | 1.107–1.554 | 0.002 | <0.001 | 1.257 | 1.076–1.468 | 0.004 |
Microvascular invasion, yes vs. no | <0.001 | 1.425 | 1.187–1.712 | <0.001 | <0.001 | 1.404 | 1.182–1.667 | <0.001 |
BCLC stage, 0 vs. A vs. B | <0.001 | NA | <0.001 | NA |
The prognostic value of MVI in subgroups
Features | Overall survival | Recurrence-free survival | ||||||
---|---|---|---|---|---|---|---|---|
Univariate
P
| Multivariate | Univariate
P
| Multivariate | |||||
HR | 95% CI |
P
| HR | 95% CI |
P
| |||
Age, ≤52 vs. >52 year | 0.751 | NA | 0.871 | NA | ||||
Gender, female vs. male | 0.434 | NA | 0.673 | NA | ||||
Hepatitis B history, yes vs. no | 0.025 | NS | 0.023 | NS | ||||
Liver cirrhosis, yes vs. no | 0.007 | 1.564 | 1.181–2.071 | 0.002 | 0.030 | 1.401 | 1.093–1.796 | 0.008 |
α-Fetoprotein, >200 vs. ≤200 ng/dL | <0.001 | 1.644 | 1.354–1.996 | <0.001 | <0.001 | 1.468 | 1.227–1.758 | <0.001 |
ALT, >75 vs. ≤75 U/L | 0.745 | NS | 0.494 | NA | ||||
γ-GT, >50 vs. ≤50 U/L | <0.001 | 1.327 | 1.074–1.640 | 0.009 | <0.001 | 1.246 | 1.030–1.509 | 0.024 |
Albumin, >35 vs. ≤35 g/L | 0.001 | NS | 0.009 | NS | ||||
Tumor size, >5 vs. ≤5 cm | <0.001 | 2.080 | 1.698–2.548 | <0.001 | <0.001 | 1.847 | 1.533–2.225 | <0.001 |
Tumor number, solitary vs. multiple | 0.837 | NA | 0.505 | NA | ||||
Tumor differentiation, III–IV vs. I–II | <0.001 | 1.272 | 1.038–1.559 | 0.020 | <0.001 | 1.250 | 1.033–1.514 | 0.022 |
Tumor encapsulation, complete vs. none | <0.001 | 1.279 | 1.056–1.549 | 0.012 | 0.001 | 1.225 | 1.026–1.463 | 0.025 |
Microvascular invasion, yes vs. no | <0.001 | 1.431 | 1.163–1.761 | 0.001 | <0.001 | 1.400 | 1.150–1.705 | 0.001 |