Establishment and validation of an intratumoral fibrosis-based nomogram for predicting aggressive recurrence after liver resection in hepatocellular carcinoma

doi:10.4240/wjgs.v18.i5.116135

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World Journal of Gastrointestinal Surgery

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1948-9366

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Retrospective Cohort Study

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World J Gastrointest Surg. May 27, 2026; 18(5): 116135
Published online May 27, 2026. doi: 10.4240/wjgs.v18.i5.116135

Table 1 Baseline clinical and pathologic characteristics of patients in training and validation cohorts

Baseline characteristics	Training (n = 855)	Validation (n = 148)	P value
Age (years), mean ± SD	53.6 ± 11.6	54.4 ± 13.1	0.460
Gender			0.052
Male	726 (84.9)	116 (78.4)
Female	129 (15.1)	32 (21.6)
Underlying liver diseases			0.254
Absence	92 (10.8)	19 (12.8)
HBV	677 (79.2)	120 (81.1)
Others	86 (10.1)	9 (6.1)
Liver cirrhosis			0.789
Absence	437 (51.1)	78 (52.7)
Presence	418 (48.9)	70 (47.3)
BCLC stage			0.758
0	80 ( 9.4)	12 (8.1)
A	775 (90.6)	136 (91.9)
B	0 (0.0)	0 (0.0)
Neutrophil (× 10⁹), median (IQR)	3.30 (2.41, 4.30)	3.30 (2.39, 4.35)	0.620
Lymphocyte (× 10⁹), median (IQR)	1.38 (1.05, 1.73)	1.31 (1.02, 1.82)	0.758
Platelet (× 10⁹), median (IQR)	155 (114, 205)	152 (85, 199)	0.088
Monocyte (× 10⁹), median (IQR)	0.33 (0.24, 0.44)	0.38 (0.28, 0.53)	0.001
Albumin (g/L), median (IQR)	38.9 (36.3, 41.6)	41.4 (37.4, 44.0)	< 0.001
Total bilirubin (µmol/L), median (IQR)	13.7 (10.5, 18.2)	12.8 (9.6, 18.7)	0.197
ALT (U/L), median (IQR)	30.3 (20.8, 47.1)	33.1 (24.7, 48.3)	0.053
AST (U/L), median (IQR)	33.6 (24.3, 48.9)	40.2 (27.2, 52.4)	0.010
Creatine (µmol/L), median (IQR)	72.1 (62.5, 81.3)	61.4 (52.6, 73.8)	< 0.001
INR, median (IQR)	1.02 (0.96, 1.09)	1.00 (0.94, 1.08)	0.023
ALBI grade			< 0.001
I	393 (46.0)	101 (68.2)
II	462 (54.0)	47 (31.8)
AFP (ng/mL)			0.464
≤ 200	531 (62.1)	87 (58.8)
> 200	324 (37.9)	61 (41.2)
Tumor size (mm), median (IQR)	50.0 (31.0, 76.0)	47.7 (32.1, 76.7)	0.823
Up to seven criteria			0.580
Within	538 (62.9)	97 (65.5)
Beyond	317 (37.1)	51 (34.5)
LI-RADS			0.792
3	30 (3.5)	6 (4.1)
4	124 (14.5)	19 (12.8)
5	615 (71.9)	105 (70.9)
M	86 (10.1)	18 (12.2)
MVI			0.645
Negative	544 (63.6)	91 (61.5)
Positive	311 (36.4)	57 (38.5)
Satellite lesion			0.921
Absence	622 (72.7)	107 (72.3)
Presence	233 (27.3)	41 (27.7)
VETC pattern			0.705
Absence	579 (67.7)	98 (66.2)
Presence	276 (32.3)	50 (33.8)
Tumor grade			0.925
Well-moderate	565 (66.1)	97 (65.5)
Poor	290 (33.9)	51 (34.5)
Intratumoral fibrosis			0.845
Low	608 (71.0)	106 (71.6)
High	252 (29.5)	42 (28.4)
Follow-up period (months), median (IQR)	43.5 (26.4, 64.8)	50.6 (25.1, 76.9)	0.072
Aggressive recurrence	191 (22.3)	37 (25.0)	0.459

Data are presented as n (%). BCLC: Barcelona Clinic Liver Cancer; ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; INR: International normalized ratio; ALBI: Albumin-bilirubin; AFP: Alpha-fetoprotein; LI-RADS: Liver imaging reporting and data system; MVI: Microvascular invasion; VETC: Vessels that encapsulate tumor clusters; IQR: Interquartile range; M: Liver imaging reporting and data system category M.

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Table 2 Baseline characteristics of the low and high intratumoral fibrosis group before and after matching in training cohort

Baseline characteristics	Before matching				After IPTW
Baseline characteristics	Low-ITF group (n = 603)	High-ITF group (n = 252)	P value	SMD	Low-ITF group (n = 855)	High-ITF group (n = 856)	P value	SMD
Age (years), mean ± SD	54.0 ± 11.6	52.6 ± 11.6	0.108	0.121	53.8 ± 11.6	52.7 ± 11.7	0.233	0.094
Gender			0.750	0.032	-		0.521	0.049
Male	93 (15.4)	36 (14.3)			132 (15.4)	117 (13.7)
Female	510 (84.6)	216 (85.7)			723 (84.6)	739 (86.3)
Underlying liver diseases			0.036	0.206	-		0.998	0.005
Absence	64 (10.6)	28 (11.1)			92 (10.7)	91 (10.6)
HBV	468 (77.6)	209 (82.9)			677 (79.2)	680 (79.4)
Others	71 (11.8)	15 (6.0)			86 (10.1)	85 (9.9)
Liver cirrhosis			0.845	0.020	-		0.580	0.043
Absence	310 (51.4)	127 (50.4)			438 (51.2)	420 (49.0)
Presence	293 (48.6)	125 (49.6)			417 (48.8)	436 (51.0)
Tumor size (mm), median (IQR)	49.00 (31.00, 70.00)	53.50 (31.00, 90.00)	0.070	0.182	50.00 (31.00, 71.58)	49.43 (29.00, 84.81)	0.676	0.095
INR, median (IQR)	1.02 (0.96, 1.08)	1.03 (0.97, 1.12)	0.059	0.170	1.02 (0.96, 1.09)	1.03 (0.97, 1.12)	0.109	0.168
Neutrophil (× 10⁹), median (IQR)	3.24 (2.39, 4.22)	3.50 (2.49, 4.58)	0.055	0.150	3.24 (2.39, 4.25)	3.48 (2.43, 4.58)	0.142	0.137
Lymphocyte (× 10⁹), median (IQR)	1.39 (1.06, 1.73)	1.37 (1.05, 1.69)	0.657	0.006	1.38 (1.05, 1.73)	1.36 (1.03, 1.68)	0.582	0.005
Platelet (× 10⁹), median (IQR)	153 (116,198)	164 (110, 217)	0.093	0.119	154 (115,200)	159 (108,220)	0.195	0.107
Monocyte (× 10⁹), median (IQR)	0.32 (0.24, 0.42)	0.34 (0.25, 0.46)	0.093	0.171	0.33 (0.24, 0.43)	0.33 (0.25, 0.45)	0.178	0.153
ALT (U/L), median (IQR)	30.4 (20.8, 48.3)	30.2 (20.8, 45.4)	0.441	0.117	30.4 (20.9, 49.0)	30.0 (20.8, 45.3)	0.325	0.145
AST (U/L), median (IQR)	33.6 (24.5, 49.9)	33.6 (23.7, 47.5)	0.875	0.038	33.7 (24.6, 50.3)	33.2 (23.5, 45.2)	0.439	0.073
Creatine (µmol/L), median (IQR)	71.7 (63.1, 81.1)	72.4 (61.8, 81.4)	0.989	0.030	71.7 (62.8, 81.0)	72.4 (62.0, 82.3)	0.770	0.004
Albumin (g/L), median (IQR)	38.9 (36.5, 41.6)	39.0 (35.9, 41.8)	0.747	0.070	38.9 (36.3, 41.6)	38.8 (35.7, 42.2)	0.853	0.057
Total bilirubin (µmol/L), median (IQR)	13.7 (10.6, 18.1)	14.1 (10.3, 18.3)	0.791	0.013	13.7 (10.6, 18.1)	14.2 (10.4, 18.5)	0.943	0.015
AFP (ng/mL)			0.642	0.041	-		0.896	0.010
≤ 200	378 (62.7)	153 (60.7)			526 (61.5)	531 (62.0)
> 200	225 (37.3)	99 (39.3)			329 (38.5)	325 (38.0)
MVI			< 0.001	0.354	-		0.979	0.002
Negative	414 (68.7)	130 (51.6)			544 (63.6)	546 (63.8)
Positive	189 (31.3)	122 (48.4)			311 (36.4)	310 (36.2)
Satellite lesion			0.003	0.228	-		0.969	0.003
Absence	457 (75.8)	165 (65.5)			623 (72.9)	625 (73.0)
Presence	146 (24.2)	87 (34.5)			232 (27.1)	231 (27.0)
VETC pattern			0.767	0.028	-		0.063	0.143
Absence	406 (67.3)	173 (68.7)			564 (66.0)	621 (72.5)
Presence	197 (32.7)	79 (31.3)			291 (34.0)	235 (27.5)
Tumor grade			0.524	0.054	-		0.603	0.040
Well-moderate	403 (66.8)	162 (64.3)			559 (65.4)	576 (67.3)
Poor	200 (33.2)	90 (35.7)			296 (34.6)	280 (32.7)

Data are presented as n (%). ITF: Intratumoral fibrosis; SMD: Standardized mean difference; IPTW: Inverse probability of treatment weighting; INR: International normalized ratio; MVI: Microvascular invasion; VETC: Vessels that encapsulate tumor clusters; HBV: Hepatitis B virus; ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; IQR: Interquartile range; AFP: Alpha-fetoprotein.

Full Size Table

Table 3 Baseline characteristics of the low and high intratumoral fibrosis group before and after matching in validation cohort

Baseline characteristics	Before matching				After IPTW
Baseline characteristics	Low-ITF group (n = 106)	High-ITF group (n = 42)	P value	SMD	Low-ITF group (n = 147)	High-ITF group (n = 150)	P value	SMD
Age (years), mean ± SD	55.2 ± 12.8	52.4 ± 14.0	0.254	0.204	54.8 ± 12.7	54.3 ± 14.0	0.845	0.039
Gender			0.797	0.089	-		0.932	0.019
Male	82 (77.4)	34 (81.0)			112 (76.2)	113 (75.3)
Female	24 (22.6)	8 (19.0)			35 (23.8)	37 (24.7)
Underlying liver diseases			0.724	0.151	-		0.901	0.090
Absence	15 (14.2)	4 (9.5)			21 (14.3)	20 (13.3)
HBV	85 (80.2)	35 (83.3)			118 (80.3)	119 (79.3)
Others	6 (5.7)	3 (7.1)			8 (5.4)	11 (7.3)
Liver cirrhosis			0.388	0.192	-		0.889	0.028
Absence	53 (50.0)	25 (59.5)			78 (53.1)	77 (51.3)
Presence	53 (50.0)	17 (40.5)			69 (46.9)	73 (48.7)
Tumor size (mm), median and IQR	46.00 (33.03, 66.75)	55.00 (30.50, 90.25)	0.434	0.235	46.00 (32.67, 68.70)	51.10 (28.51, 89.40)	0.831	0.147
INR, median and IQR	1.00 (0.94, 1.08)	1.02 (0.94, 1.07)	0.892	0.032	1.00 (0.94, 1.08)	1.01 (0.94, 1.08)	0.784	0.059
Neutrophil (× 10⁹), median and IQR	3.07 (2.38, 4.25)	3.51 (2.52, 4.63)	0.339	0.103	3.05 (2.35, 4.23)	3.44 (2.29, 4.75)	0.335	0.155
Lymphocyte (× 10⁹), median and IQR	1.32 (1.02, 1.80)	1.23 (1.02, 1.86)	0.837	0.095	1.32 (1.03, 1.81)	1.21 (1.02, 1.66)	0.534	0.189
Platelet (× 10⁹), median and IQR	155(85, 205)	138(87, 193)	0.782	0.147	154 (82,201)	134 (80,190)	0.686	0.180
Monocyte (× 10⁹), median and IQR	0.36 (0.28, 0.50)	0.41 (0.30, 0.54)	0.373	0.039	0.36 (0.26, 0.49)	0.41 (0.31, 0.53)	0.305	0.051
ALT (U/L), median and IQR	32.7 (21.7, 46.5)	37.1 (29.6, 50.0)	0.137	0.104	32.7 (20.4, 45.9)	34.1 (22.8, 47.4)	0.706	0.005
AST (U/L), median and IQR	38.7 (26.5, 51.0)	41.7 (31.2, 53.0)	0.249	0.130	38.8 (26.5, 51.0)	39.4 (26.6, 52.4)	0.852	0.016
Creatine (umol/L), median and IQR	61.0 (52.9, 72.0)	64.1 (51.5, 75.6)	0.521	0.020	61.0 (52.0, 72.0)	64.2 (49.0, 76.3)	0.496	0.052
Albumin (g/L), median and IQR	41.3 (37.3, 43.8)	41.6 (38.0, 45.3)	0.308	0.147	41.2 (36.5, 43.8)	41.5 (37.0, 44.6)	0.460	0.122
Total bilirubin (umol/L), median and IQR	11.7 (9.2, 17.6)	14.6 (10.8, 19.3)	0.093	0.313	12.2 (9.5, 17.7)	11.6 (9.5, 16.6)	0.905	0.023
AFP (ng/mL)			0.055	0.387	-		0.779	0.054
≤ 200	68 (64.2)	19 (45.2)			88 (59.9)	94 (62.7)
> 200	38 (35.8)	23 (54.8)			59 (40.1)	56 (37.3)
MVI			0.620	0.124	-		0.992	0.002
Negative	67 (63.2)	24 (57.1)			94 (63.9)	96 (64.0)
Positive	39 (36.8)	18 (42.9)			53 (36.1)	54 (36.0)
Satellite lesion			0.956	0.047	-		0.388	0.159
Absence	76 (71.7)	31 (73.8)			107 (72.8)	120 (80.0)
Presence	30 (28.3)	11 (26.2)			40 (27.2)	30 (20)
VETC pattern			0.373	0.196	-		0.356	0.186
Absence	73 (68.9)	25 (59.5)			100 (68.0)	89 (59.3)
Presence	33 (31.1)	17 (40.5)			47 (32.0)	61 (40.7)
Tumor grade			0.054	0.385	-		0.933	0.016
Well-moderately	75 (70.8)	22 (52.4)			96 (65.3)	97 (64.7)
Poorly	31 (29.2)	20 (47.6)			51 (34.7)	53 (35.3)

Data are presented as n (%). ITF: Intratumoral fibrosis; SMD: Standardized mean difference; INR: International normalized ratio; MVI: Microvascular invasion; VETC: Vessels that encapsulate tumor clusters; ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; IQR: Interquartile range; AFP: Alpha-fetoprotein.

Full Size Table

Table 4 Univariable and multivariable Fine-Gray analysis in training cohort

Characteristics	Univariable Fine-Gray analysis			Multivariable Fine-Gray analysis
Characteristics	β value	SHR 95%CI	P value	β value	SHR 95%CI	P value
Age (years)	-0.008	0.992 (0.980, 1.000)	0.210	-	-	-
Tumor size (mm)	0.015	1.020 (1.010, 1.020)	< 0.001	0.012	1.010 (1.010, 1.020)	< 0.001
Neutrophil (× 10⁹)	0.162	1.180 (1.090, 1.260)	< 0.001	0.083	1.090 (1.000, 1.180)	0.046
Lymphocyte (× 10⁹)	-0.125	0.882 (0.690, 1.130)	0.320	-	-	-
Platelet (× 10⁹)	0.004	1.000 (1.000, 1.010)	< 0.001	-	-	-
Monocyte (× 10⁹)	1.370	3.950 (2.300, 6.800)	< 0.001	-	-	-
Albumin (g/L)	-0.040	0.961 (0.927, 0.996)	0.028	-	-	-
Total bilirubin (µmol/L)	-0.016	0.985 (0.968, 1.000)	0.068	-	-	-
ALT (U/L)	-0.001	0.999 (0.995, 1.000)	0.480	-	-	-
AST (U/L)	0.002	1.000 (0.999, 1.000)	0.240	-	-	-
Creatine (µmol/L)	-0.002	1.000 (0.992, 1.010)	0.960	-	-	-
INR	1.250	3.500 (1.070, 11.400)	0.038	-	-	-
Intratumoral fibrosis
Low	Ref	-	-	-	-	-
High	1.650	5.230 (3.900, 7.010)	< 0.001	1.557	4.750 (3.530, 6.370)	< 0.001
MVI
Negative	Ref	-	-	-	-	-
Positive	1.450	4.280 (3.180, 5.760)	< 0.001	1.165	3.200 (2.360, 4.350)	< 0.001
Gender
Female	Ref	-	-	-	-	-
Male	0.198	1.220 (0.803, 1.850)	0.350	-	-	-
Liver cirrhosis
Absence	Ref	-	-	-	-	-
Presence	-0.050	0.951 (0.716, 1.260)	0.730	-	-	-
AFP (ng/mL)
≤ 200	Ref	-	-	-	-	-
> 200	0.481	1.620 (1.220, 2.150)	< 0.001	-	-	-
Tumor grade
Well/moderate	Ref	-	-	-	-	-
Poor	0.560	1.750 (1.320, 2.330)	< 0.001	-	-	-
Satellite lesion
Absence	Ref	-	-	-	-	-
Presence	0.821	2.270 (1.700, 3.040)	< 0.001	-	-	-
VETC pattern
Absence	Ref	-	-	-	-	-
Presence	0.453	1.570 (1.180, 2.100)	0.002	-	-	-
Underlying liver diseases
Absence	Ref	-	-	-	-	-
HBV	0.078	1.081 (0.679, 1.720)	0.740	-	-	-
Others	-0.234	0.791 (0.408, 1.540)	0.490	-	-	-

SHR: Subdistribution hazard ratio; CI: Confidence interval; ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; INR: International normalized ratio; AFP: Alpha-fetoprotein; MVI: Microvascular invasion; VETC: Vessels that encapsulate tumor clusters; Ref: Reference.

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Citation: Deng QY, Leng HQ, Wang TC, Hu C. Establishment and validation of an intratumoral fibrosis-based nomogram for predicting aggressive recurrence after liver resection in hepatocellular carcinoma. World J Gastrointest Surg 2026; 18(5): 116135
URL: https://www.wjgnet.com/1948-9366/full/v18/i5/116135.htm
DOI: https://dx.doi.org/10.4240/wjgs.v18.i5.116135

Deng QY, Leng HQ, Wang TC, Hu C. Establishment and validation of an intratumoral fibrosis-based nomogram for predicting aggressive recurrence after liver resection in hepatocellular carcinoma. World J Gastrointest Surg 2026; 18(5): 116135 [DOI: 10.4240/wjgs.v18.i5.116135]

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