Recurrence after surgery for hepatocellular carcinoma: “The seed and the soil” - a multicentre retrospective cohort study

doi:10.4254/wjh.120213

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World Journal of Hepatology

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1948-5182

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Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA

Retrospective Cohort Study

Copyright: ©Author(s) 2026. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution-NonCommercial (CC BY-NC 4.0) license. No commercial re-use. See permissions. Published by Baishideng Publishing Group Inc.

World J Hepatol. Jun 27, 2026; 18(6): 120213
Published online Jun 27, 2026. doi: 10.4254/wjh.120213

Table 1 Baseline characteristics of patients with hepatocellular carcinoma undergoing primary liver resection

	Baseline characteristics of cohort (n = 235)	Recurrence, n = 94 (40)	No recurrence, n = 141 (60)
Patient factors
Recurrence by aetiology
HCV	71 (30)	36 (51)	35 (49)
HBV	94 (40)	33 (35)	61 (65)
MASLD/alcohol	70 (30)	25 (36)	45 (34)
Age, years [median (q1-q3)]	64 (57-70)	64 (56-71)	65 (57-70)
Male sex	183 (78)	74 (40)	109 (60)
Diabetes (T2DM)	79 (34)	28 (35)	51 (65)
Liver factors
Cirrhosis
No	92 (39)	35 (38)	57 (62)
Yes	143 (61)	59 (41)	84 (59)
Child Pugh
No cirrhosis	92 (39)	35 (38)	57 (62)
A5	112 (48)	43 (38)	69 (62)
≥ A6	31 (13)	16 (52)	15 (48)
MELD 3.0 score
No cirrhosis	92 (39)	35 (38)	57 (62)
6	27 (11)	6 (22)	21 (78)
7	35 (15)	17 (49)	18 (51)
8	31 (13)	13 (42)	18 (58)
≥ 9	50 (21)	23 (46)	27 (54)
ALBI grade
1	157 (67)	61 (39)	96 (61)
≥ 2	78 (33)	33 (42)	45 (58)
Platelet count
≤ 150	62 (26)	23 (37)	39 (63)
> 150	173 (74)	71 (41)	102 (59)
Tumour factors
AFP (ng/mL)
< 400	188 (80)	75 (40)	113 (60)
≥ 400	22 (9)	9 (41)	13 (59)
Unknown AFP at diagnosis	25 (11)	10 (40)	15 (60)
BCLC
0	42 (18)	14 (33)	28 (67)
A	159 (68)	66 (42)	93 (58)
B	20 (8)	9 (45)	11 (55)
C	14 (6)	5 (36)	9 (64)
UCSF criteria
In	195 (83)	78 (40)	117 (60)
Out	40 (17)	16 (40)	24 (60)
Number of nodules
1	192 (82)	80 (42)	112 (58)
2	29 (12)	9 (31)	20 (69)
≥ 3	14 (6)	5 (36)	9 (64)
Size of largest nodule/s
< 3 cm	100 (43)	36 (36)	64 (64)
3-4.9 cm	68 (29)	27 (40)	41 (60)
5-10 cm	50 (22)	26 (52)	24 (48)
> 10 cm	17 (7)	5 (29)	12 (71)
Presence of macroscopic vascular invasion (or tumour rupture/bleed)
Yes	14 (6)	5 (36)	9 (74)
No	221 (94)	89 (40)	132 (60)

Clinical, liver disease-related, and tumour-related characteristics of the study cohort stratified by recurrence status. Values are presented as n (%) or median (interquartile range). We performed univariate (unadjusted) analysis and identified factors associated with hepatocellular carcinoma recurrence including age, the presence of cirrhosis, Child-Pugh score, model for end-stage liver disease 3.0 score, albumin-bilirubin grade grade, aetiology, and University of California San Francisco criteria, Barcelona Clinic Liver Cancer staging system (BCLC) stage, nodule size and macrovascular invasion (Table 2). Multivariate analysis found the albumin-bilirubin score, if ≥ 2; adjusted hazard ratio (aHR): 2.24 (1.43-3.52) P < 0.001, the presence of cirrhosis; aHR: 2.21 (1.42-3.43) P < 0.001 and those with Barcelona Clinic Liver Cancer stage B/C; aHR: 2.51 (1.41-4.47) P = 0.002 as independent predictors of recurrence. AFP: Alpha-fetoprotein; ALBI: Albumin-bilirubin grade; BCLC: Barcelona Clinic Liver Cancer; HBV: Hepatitis B virus; HCV: Hepatitis C virus; MASLD: Metabolic dysfunction-associated steatotic liver disease; MELD: Model for end-stage liver disease; T2DM: Type 2 diabetes mellitus; UCSF: University of California San Francisco criteria.

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Table 2 Factors associated with hepatocellular carcinoma recurrence following primary liver resection, Cox proportional hazard model assessing hepatocellular carcinoma recurrence following primary liver resection (n = 235)

		Unadjusted model		Adjusted model 1		Adjusted model 2		Adjusted model 3		Adjusted model 4
Characteristics	Rate of recurrence (95%CI), per 100 person-years	HR (95%CI)	P value	HR (95%CI)	P value	HR (95%CI)	P value	HR (95%CI)	P value	HR (95%CI)	P value
Patient factors
Age, year	N/A	1.02 (1.01-1.04)	0.019	1.03 (1.00-1.05)	0.019	1.02 (1.00-1.05)	0.043	1.02 (1.00-1.04)	0.108	1.03 (1.01-1.05)	0.017
Sex
Male	10.5 (8.4-13.2)	1.00
Female	11.3 (7.3-17.6)	1.14 (0.70-1.88)	0.598
Diabetes (T2DM)
Nil diabetes	10.8 (8.5-13.8)	1.00
T2DM	10.3 (7.1-15.0)	1.09 (0.70-1.71)	0.704
Liver factors
Cirrhosis
No	7.8 (5.6-10.9)	1.00								1.00
Yes	13.5 (10.5-17.3)	2.21 (1.42-3.43)	< 0.001							2.03 (1.27-3.25)	0.003
Child Pugh
No cirrhosis	8.0 (5.8-11.2)	1.00		1.00
A5	11.8 (8.8-15.9)	1.87 (1.17-2.97)	0.008	1.73 (1.06-2.83)	0.029
> A6	19.7 (12.1-32.2)	3.24 (1.76-5.98)	< 0.001	2.85 (1.50-5.42)	0.001
MELD 3.0 score
No cirrhosis	7.8 (5.6-10.9)	1.00				1.00
6	6.6 (2.9-14.6)	1.18 (0.48-2.86)	0.718			1.13 (0.46-2.80)	0.790
7	12.1 (7.5-19.5)	1.68 (0.93-3.04)	0.083			1.51 (0.81-2.82)	0.191
8	16.2 (9.4-27.8)	3.06 (1.57-5.94)	0.001			2.77 (1.35-5.67)	0.005
≥ 9	18.0 (12.1-26.9)	3.29 (1.89-5.71)	< 0.001			2.97 (1.68-5.27)	< 0.001
ALBI grade
1	9.2 (7.1-11.8)	1.00						1.00
≥ 2	15.2 (10.8-21.4)	2.24 (1.43-3.52)	< 0.001					2.02 (1.27-3.21)	0.003
Tumour factors
Aetiology of HCC
HBV	8.8 (6.3-12.4)	1.00		1.00		1.00		1.00		1.00
HCV	14.6 (10.5-20.3)	1.75 (1.08-2.81)	0.022	1.22 (0.73-2.03)	0.448	1.18 (0.70-1.99)	0.532	1.45 (0.89-2.35)	0.132	1.20 (0.72-1.99)	0.478
MASLD/ETOH	9.6 (6.5-14.1)	1.27 (0.74-2.17)	0.378	0.91 (0.51-1.62)	0.758	0.85 (0.48-1.53)	0.595	0.99 (0.56-1.73)	0.966	0.87 (0.49-1.55)	0.644
AFP (ng/mL)
< 400 (n = 190)	10.2 (8.1-12.8)	1.00
≥ 400 (n = 27)	15.7 (8.2-30.2)	1.53 (0.76-3.10)	0.234
BCLC
0-A	9.9 (7.9-12.3)	1.00		1.00		1.00		1.00		1.00
B-C	19.9 (11.8-33.7)	2.51 (1.41-4.47)	0.002	2.01 (1.12-3.60)	0.019	2.23 (1.23-4.03)	0.008	2.38 (1.33-4.25)	0.003	2.05 (1.15-3.67)	0.015
Number of nodules
1	10.3 (8.2-12.8)	1.00
2	13.9 (7.3-26.8)	1.77 (0.88-3.59)	0.112
≥ 3	13.5 (5.6-32.3)	1.45 (0.59-3.60)	0.418
Size of largest nodule/s
< 3 cm	8.1 (5.9-11.3)	1.00
3-4.9 cm	11.0 (7.5-16.1)	1.50 (0.90-2.49)	0.118
5-10 cm	17.2 (11.7-25.3)	2.67 (1.58-4.52)	< 0.001
> 10 cm	11.9 (5.0-28.6)	1.87 (0.73-4.82)	0.195
Presence of macroscopic vascular invasion (or tumour rupture/bleed)
No	10.3 (8.4-12.7)	1.00
Yes	26.8 (11.2-64.4)	2.96 (1.19-7.39)	0.020

Univariate and multivariate Cox proportional hazards regression analyses evaluating factors associated with recurrence following curative-intent liver resection. Results are presented as hazard ratios with 95% confidence intervals. AFP: Alpha-fetoprotein; ALBI: Albumin-bilirubin grade; BCLC: Barcelona Clinic Liver Cancer; CP: Child-Pugh score; MELD: Model for end-stage liver disease; HR: Hazard ratio; HCV: Hepatitis C virus; MASLD: Metabolic dysfunction-associated steatotic liver disease; ETOH: Chronic ethanol; HBV: Hepatitis B virus; HCC: Hepatocellular carcinoma; MELD: Model for end-stage liver disease; T2DM: Type 2 diabetes mellitus.

Full Size Table

Table 3 Recurrence risk according to the number of pre-operative risk factors (cirrhosis, albumin-bilirubin grade ≥ 2, Barcelona Clinic Liver Cancer staging system stage B/C)

Number of risk factors	Criteria present	aHR (95%CI)	P value	n (%)
0	None	Reference	Reference	60 (26)
1	Any one of: Cirrhosis, ALBI ≥ 2, or BCLC stage B/C	2.74 (1.57-4.76)	< 0.001	102 (43)
2	Any two	4.32 (2.29-8.12)	< 0.001	62 (26)
3	All three	7.53 (2.47-22.93)	< 0.001	10 (4)

aHR: Adjusted hazard ratio; CI: Confidence interval; ALBI: Albumin-bilirubin; BCLC: Barcelona Clinic Liver Cancer.

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Citation: Blackmore C, Lockart I, Gandy G, Yeoh YKJ, Flynn C, Prince DS, Dore G, Danta M, George J, Alavi M, Farooque Y, Hajarizadeh B, Levy MT. Recurrence after surgery for hepatocellular carcinoma: “The seed and the soil” - a multicentre retrospective cohort study. World J Hepatol 2026; 18(6): 120213
URL: https://www.wjgnet.com/1948-5182/full/v18/i6/120213.htm
DOI: https://dx.doi.org/10.4254/wjh.120213

Blackmore C, Lockart I, Gandy G, Yeoh YKJ, Flynn C, Prince DS, Dore G, Danta M, George J, Alavi M, Farooque Y, Hajarizadeh B, Levy MT. Recurrence after surgery for hepatocellular carcinoma: “The seed and the soil” - a multicentre retrospective cohort study. World J Hepatol 2026; 18(6): 120213 [DOI: 10.4254/wjh.120213]

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