Prediction of Non-Transplantable Recurrence After Liver Resection for Solitary Hepatocellular Carcinoma

Figures & data

Figure 1 Flowchart of inclusion and exclusion criteria for the study.

Table 1 Baseline Characteristics

Variable	Overall (n = 253)	Non-NTR (n = 219)	NTR (n = 34)	p-value*
Sex				>0.9
Male	201 (79%)	174 (79%)	27 (79%)
Female	52 (21%)	45 (21%)	7 (21%)
Age				0.2
≤ 50 years	86 (34%)	71 (32%)	15 (44%)
> 50 years	167 (66%)	148 (68%)	19 (56%)
Hepatitis				>0.9
No	17 (6.7%)	15 (6.8%)	2 (5.9%)
HBsAg	220 (87%)	190 (86.8%)	30 (88.2%)
HCsAg	16 (6.3%)	14 (6.4%)	2 (5.9%)
Cirrhosis				0.7
No	67 (26%)	59 (27%)	8 (24%)
Yes	186 (74%)	160 (73%)	26 (76%)
AFP				0.3
≤ 400 ng/mL	204 (81%)	179 (82%)	25 (74%)
> 400 ng/mL	49 (19%)	40 (18%)	9 (26%)
ALT				0.4
≤ 40 U/L	152 (60%)	134 (61%)	18 (53%)
> 40 U/L	101 (40%)	85 (39%)	16 (47%)
AST				0.4
≤ 40 U/L	172 (68%)	151 (69%)	21 (62%)
> 40 U/L	81 (32%)	68 (31%)	13 (38%)
Size				0.093
≤ 20mm	30 (12%)	29 (13%)	1 (3%)
> 20mm	223 (88%)	190 (87%)	33 (97%)
ALBI				0.4
1	91 (36%)	81 (37%)	10 (29%)
2	162 (64%)	138 (63%)	24 (71%)
PLT				0.5
≤ 150×10^9/L	135 (53%)	115 (53%)	20 (59%)
> 150×10^9/L	118 (47%)	104 (47%)	14 (41%)
Child–Pugh				>0.9
A	246 (97%)	213 (97%)	33 (97%)
B	7 (3%)	6 (3%)	1 (3%)
Morphological
Regular	147 (58.1%)	129 (58.9%)	18 (52.9%)	0.6
Irregular	106 (41.9%)	90 (41.1%)	16 (47.1%)

Notes: Categorical variables are presented as n (%). *Wilcoxon rank sum test; Pearson’s Chi-squared test; Fisher’s exact test.

Abbreviations: AFP, Alpha-fetoprotein; ALT, Alanine aminotransferase; AST, Aspartate aminotransferase; ALBI, albumin-bilirubin; PLT, platelets, regular Nodular, Irregular Confluent nodular or with extrahepatic growth.

Table 2 Imaging Features with NTR

Variable	Overall (n = 253)	Non-NTR (n = 219)	NTR (n = 34)	p-value*
APHE				0.027
Non-rim APHE	219 (87%)	194 (89%)	25 (74%)
None or rim APHE	34 (13%)	25 (11%)	9 (26%)
Washout				0.067
None	27 (11%)	20 (9.1%)	7 (21%)
Washout	226 (89%)	199 (91%)	27 (79%)
Capsule				0.015
None	56 (22%)	43 (20%)	13 (38%)
Capsule	197 (78%)	176 (80%)	21 (62%)
Satellite nodules				0.7
No	240 (95%)	208 (95%)	32 (94%)
Yes	13 (5%)	11 (5.0%)	2 (6%)
Peritumoral enhancement				0.6
No	165 (65%)	144 (66%)	21 (62%)
Yes	88 (35%)	75 (34%)	13 (38%)
Mosaic architecture				0.8
No	94 (37%)	82 (37%)	12 (35%)
Yes	159 (63%)	137 (63%)	22 (65%)
Intratumor ischemia				0.1
No	187 (74%)	158 (72%)	29 (85%)
Yes	66 (26%)	61 (28%)	5 (15%)
Intratumor hemorrhage				0.4
No	209 (83%)	179 (82%)	30 (88%)
Yes	44 (17%)	40 (18%)	4 (12%)
Fat in mass				0.5
No	196 (77%)	168 (77%)	28 (82%)
Yes	57 (23%)	51 (23%)	6 (18%)

Notes: Categorical variables are presented as n (%).*Wilcoxon rank sum test; Fisher’s exact test; Pearson’s Chi-squared test.

Abbreviation: APHE, arterial phase hyperenhancement.

Figure 2 (A) A streamplot to show pre - and post-operative HCC status.(NTR: Non-transplantable Recurrence T Transplantable TR: Transplantable Recurrence NR: Non-Recurrence) (B) Recurrence stratification by NTRScore after surgical resection for hepatocellular carcinoma (NTR: Non-transplantable Recurrence TR: Transplantable Recurrence NR: Non-Recurrence) (C) NTRScore categories in Kaplan-Meier curves for recurrence-free survival (RFS) in HCC patients (D) NTRScore categories in Kaplan-Meier curves for overall survival (OS) in HCC patients.

Table 3 Univariate and Multivariate Cox Analyses for NTR of HCC Patients

Characteristic	Univariate			Multivariate
	HR	95% CI	P-value	HR	95% CI	p-value
AFP(> 10 ng/mL)	2.86	1.33, 6.13	0.007*	3.42	1.54, 7.63	0.003
Size (>20 mm)	4.6	0.63, 33.6	0.13
APHE	2.73	1.27, 5.85	0.01*	2.23	1.03, 4.81	0.041
Washout	0.44	0.19, 1.02	0.056*	0.35	0.15, 0.84	0.019
Capsule	0.4	0.20, 0.80	0.009*	0.44	0.22, 0.88	0.021
Satellite nodules	1.24	0.30, 5.19	0.77
Peritumoral enhancement	1.15	0.57, 2.30	0.69
Mosaic architecture	1.06	0.52, 2.14	0.87
Intratumoral hypoperfusion	0.49	0.19, 1.28	0.15
Intratumor hemorrhage	0.65	0.23, 1.85	0.42
Fat in mass	0.69	0.29, 1.67	0.41

Note: *Referred to p<0.1 in multivariable analysis.

Abbreviations: HR, Hazard Ratio; CI, Confidence Interval; AFP, Alpha-fetoprotein; APHE, Arterial phase hyperenhancement.

Figure 3 The red arrows are tumors, the blue arrows are the recurrence tumors. 1. Low: a 61-year-old man had a preoperative AFP of 1.96 ng/mL. According to (a-c) it was found that the patient with APHE, capsule, washout got a score of −1.87. (d) showed that the patient had no recurrence. 2. Medium: A 57-year-old man had a preoperative AFP greater than 1210 ng/mL. According to the (e-g) it was found that the patient with APHE, capsule and washout got a score of 0.64. (h) showed that the patient had recurrence, but it was transplanted recurrence. 3. High: A 41-year-old man had a preoperative AFP of 332.4 ng/mL. According to the (i-k), the patient had washout and APHE without capsule and the score was 0.19. (l) showed multiple recurrent tumors in the patient.