Table 1.
Clinical variables | Recurrence | Metastasis | Overall survival | ||||||||||||
Univariate analysis | Multivariate analysis | Univariate analysis | Multivariate analysis | Univariate analysis | Multivariate analysis | ||||||||||
Rec (+) n=144 | Rec (−) n=152 | P value | HR (95% CI) |
P value | Metastasis (+) n=61 | Metastasis (−) n=235 | P value | HR (95% CI) |
P value | Death n=84 | Alive n=212 | P value | HR (95% CI) |
P value | |
Age (years) | 57.6±9.9 | 55.7±9.7 | 0.094 | 58.0±9.9 | 56.3±9.7 | 0.224 | 57.0±11.0 | 56.5±9.4 | 0.715 | ||||||
Male sex | 118 (81.9%) | 131 (86.2%) | 0.318 | 46 (75.5%) | 203 (86.4%) | 0.037 | 0.506 (0.271 to 0.945) |
0.032 | 69 (82.1%) | 180 (84.9%) | 0.558 | ||||
Cause of HCC | 0.526 | 0.974 | 0.254 | ||||||||||||
Alcohol | 14 | 13 | 5 | 21 | 8 | 18 | |||||||||
HBV | 109 | 125 | 50 | 184 | 63 | 171 | |||||||||
HCV | 16 | 9 | 4 | 21 | 10 | 15 | |||||||||
NAFLD | 2 | 3 | 1 | 4 | 0 | 5 | |||||||||
Undetermined | 3 | 3 | 1 | 5 | 3 | 3 | |||||||||
AFP (ng/mL) | 3290±19 017 | 3011±15 882 | 0.891 | 8684±31 684 | 1710±10 786 | 0.005 | 5930±25 840 | 2043±12 597 | 0.084 | ||||||
PIVKA II (mAU/mL) | 1580±8915 | 2299±10 634 | 0.549 | 4150±15 009 | 1365±7843 | 0.057 | 3067±12 679 | 1500±8404 | 0.236 | ||||||
PT (%) | 98.3±13.8 | 98.4±19.2 | 0.967 | 96.1±14.5 | 99.0±17.3 | 0.231 | 94.3±12.9 | 100.0±17.9 | 0.008 | ||||||
PLT (103/mm3) | 159±71 | 149±73 | 0.233 | 165±76 | 150±71 | 0.152 | 145±69.7 | 157±73.3 | 0.224 | ||||||
ALT (IU/L) | 46.0±33.3 | 36.6±19.9 | 0.003 | 35.7±19.0 | 42.6±29.3 | 0.083 | 0.982 (0.968 to 0.996) |
0.014 | 41.5±25.1 | 41.0±26.5 | 0.887 | ||||
Albumin (g/dL) | 4.15±0.42 | 4.15±0.55 | 0.843 | 4.06±0.43 | 4.18±0.50 | 0.111 | 0.515 (0.302 to 0.879) |
0.015 | 3.9±0.4 | 4.3±0.5 | <0.001 | 0.517 (0.355 to 0.752) |
0.001 | ||
Total bilirubin (mg/dL) | 0.8±0.5 | 1.3±3.7 | 0.132 | 0.9±0.6 | 1.1±3.0 | 0.545 | 0.9±0.5 | 1.2±3.1 | 0.437 | ||||||
MELD score | 5.3±3.2 | 5.3±4.5 | 0.915 | 4.8±3.3 | 5.5±4.1 | 0.160 | 5.6±3.1 | 5.2±4.2 | 0.41 | ||||||
CTP (A/B) | 140/4 | 140/12 | 0.052 | 58/3 | 222/13 | 0.850 | 79/5 | 201/11 | 0.780 | ||||||
Underlying liver disease (CH/LC) | 27/117 | 36/116 | 0.300 | 27/117 | 36/116 | 0.300 | 13/71 | 50/162 | 0.124 | ||||||
Tumour size (cm) | 5.1±3.0 | 4.0±3.6 | <0.001 | 0.587 (0.394 to 0.875) |
0.009 | 6.3±3.9 | 4.0±3.0 | <0.001 | 1.114 (1.058 to 1.173) |
<0.001 | 5.2±3.3 | 4.2±3.3 | 0.019 | ||
<3 cm/>3 cm | 38/106 | 82/70 | <0.001 | 13/48 | 107/128 | 0.001 | 25/59 | 95/117 | 0.017 | ||||||
Tumour number (single/multiple) | 123/11 | 131/21 | 0.850 | 54/7 | 200/35 | 0.495 | 72/12 | 182/30 | 0.976 | ||||||
E-S grade (I–II/III–IV) | 59/95 | 85/67 | <0.001 | 14/47 | 120/115 | <0.001 | 0.499 (0.265 to 0.940) |
0.031 | 29/55 | 105/107 | 0.019 | ||||
Microvascular invasion | 58/86 | 31/121 | <0.001 | 2.320 (1.618 to 3.327) |
<0.001 | 26/35 | 63/172 | 0.016 | 2.123 (1.189 to 3.790) |
0.011 | 40/44 | 105/107 | <0.001 | 2.931 (1.886 to 4.554) |
<0.001 |
Lymphovascular invasion | 37/107 | 12/140 | <0.001 | 1.856 (1.245 to 2.767) |
0.002 | 18/43 | 31/204 | 0.002 | 17/67 | 32/180 | 0.286 | ||||
Tumour satellites | 13/121 | 16/136 | 0.665 | 10/51 | 19/216 | 0.052 | 7/77 | 22/190 | 0.594 | ||||||
Resection margin | 4/140 | 0/152 | 0.055 | 0/61 | 4/231 | 0.584 | 2/82 | 2/210 | 0.319 | ||||||
Tumour capsule | 37/107 | 32/120 | 0.345 | 18/43 | 51/184 | 0.199 | 21/63 | 48/164 | 0.665 | ||||||
Tumour septum | 48/96 | 56/96 | 0.527 | 24/37 | 80/155 | 0.440 | 31/53 | 73/139 | 0.668 | ||||||
TonEBP expression | |||||||||||||||
TonEBP in non-tumour (tNT 0/1) |
48/96 | 82/70 | <0.001 | 0.566 (0.397 to 0.807) |
0.002 | 20/41 | 110/125 | 0.049 | 0.513 (0.288 to 0.914) |
0.024 | 32/52 | 98/114 | 0.204 | ||
TonEBP in tumour (tT 0/1) |
29/115 | 51/101 | 0.009 | 10/51 | 70/165 | 0.036 | 15/69 | 65/147 | 0.025 | 0.547 (0.311 to 0.754) |
0.036 |
tNT0 and tNT1 are defined in figure 1I; tT0 and tT1 are defined in figure 1J. A multivariate analysis was carried out to identify the independent predictor for recurrence and survival using the Cox regression hazard model.
AFP, alpha-fetoprotein; ALT, alanine transaminase; CH, chronic hepatitis; CTP, Child-Turcotte-Pugh class; E-S grade, Edmondson-Steiner grade; HCC, hepatocellular carcinoma; LC, liver cirrhosis; MELD score, model for end-stage liver disease score; NAFLD, non-alcoholic fatty liver disease; PIVKA II, protein induced by vitamin K absence or antagonist II; PLT, platelet; PT, prothrombin time; Rec (+), recurrence; Rec (−), non-recurrence; TonEBP, TonEBP, tonicity-responsive enhancer-binding protein.