Adjuvant transarterial chemoembolization for solitary large hepatocellular carcinoma by microvascular invasion and/or satellite lesion burden：A Multi-Center Retrospective Study

Adjuvant transarterial chemoembolization for solitary large hepatocellular carcinoma by microvascular invasion and/or satellite lesion burden：A Multi-Center Retrospective Study | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Adjuvant transarterial chemoembolization for solitary large hepatocellular carcinoma by microvascular invasion and/or satellite lesion burden：A Multi-Center Retrospective Study Chuwen Chen, Qing Tao, Changli Lu, Yu Zhang, Deng Shasha, Shusheng Leng, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7792877/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 5 You are reading this latest preprint version Abstract Background: Adjuvant therapy for solitary large hepatocellular carcinoma (SLHCC) remained unclear. Methods: 1292 SLHCC patients treated with hepatectomy between January 2010 and December 2020 were included in this retrospective cohort study investigating adjuvant transarterial chemoembolization (TACE), recurrence free survival (RFS) and overall survival (OS). Results: Among the study cohort, 571 SLHCC patients (44.2%) with microvascular invasion and/or satellite lesion (mVI/S) burden were classified as aggressive SLHCC, while 721 patients without mVI/S were classified as non-aggressive SLHCC, showing significantly better 10-year OS rates (51.7% versus 21.2%, p <0.001). Adjuvant TACE could significantly improve RFS in non-aggressive SLHCC patients, with 5- and 10-year RFS rates of 56.8% and 25.3% (vs. 43.7% and 24.8% in untreated patients, p =0.043), a finding confirmed by inverse probability of treatment weighting (IPTW) analysis ( p =0.018). However, adjuvant TACE did not significantly impact OS in this group( p =0.52; IPTW: p =0.249). For aggressive SLHCC patients, adjuvant TACE showed benefits in both RFS (5-year: 35.6% vs 24.5%; 10-year: 18.1% vs 11.4%, p <0.001; IPTW: p <0.001)) and OS (5-year: 52.4% vs 40.9%; 10-year: 25.5% vs 19.2%, p =0.033; IPTW: p =0.029). The mVI/S burden was independent predictors of RFS (HR：1.53, 95%CI:1.32-1.76, p <0.001) and OS (HR：1.79, 95%CI:1.52-2.11, p <0.001) for SLHCC. Adjuvant TACE was associated with RFS (HR：0.74 95%CI:0.58-0.93, p =0.011) but not OS (HR：0.91, 95%CI:0.68-1.22, p =0.523) for non-aggressive SLHCC, while demonstrating significant benefit for RFS (HR：0.68, 95%CI:0.53-0.87, p <0.001) and OS (HR：0.72, 95%CI:0.57-0.91, p =0.007) for aggressive SLHCC. Conclusions: The mVI/S burden identified aggressive SLHCC subtypes. Adjuvant TACE improved both RFS and OS in aggressive SLHCC, but only RFS (not OS) in non-aggressive cases. microvascular invasion satellite lesion solitary hepatocelluar carcinoma hepatectomy adjuvant therapy Figures Figure 1 Figure 2 Figure 3 Highlight 1. Solitary large HCC (SLHCC) should be further classified as non-aggressive SLHCC and aggressive SLHCC based on microvascular invasion and/or satellite lesion (mVI/S) burden. Non-aggressive SLHCC patients had long term survival, comparable to patients with early-stage HCC. 2. For those with aggressive SLHCC, long-term survival was dismal. Postoperative adjuvant transarterial chemoembolization (TACE) showed benefits in both recurrence free survival (RFS) and overall survival (OS). 3. Adjuvant TACE could improve RFS in non-aggressive SLHCC patients. However, Adjuvant TACE did not significantly impact OS. Introduction Hepatocellular carcinoma (HCC) was one of the most frequent cancers worldwide, with China alone accounting for about 50% of the total number of cases and deaths 1 . Solitary large HCC (> 5cm, SLHCC) was a subgroup of HCCs, which caught much attention for its proper position. Current staging systems exhibited significant discordance in classifying SLHCC. Barcelona Clinic Liver Cancer (BCLC) staging system was widely used to evaluate HCC of patients including tumor stage and treatment guidance. BCLC system categorizes SLHCC as early-stage (Stage A) 2 , while the AJCC 8th edition incorporates vascular invasion status to differentiate SLHCC into T1b and T2 classifications, respectively 3 . The CNLC stage system defined SLHCC as Ib stage, which had worse prognosis than that of small HCC 4 . Yang et al 5 suggested that tumor aggressive-related genes seem had no correlation with the tumor size. Tumor biology and underlying liver other than tumor size determined prognosis 6 . Study based on Surveillance Epidemiology and End Results (SEER) database, suggested that for solitary HCC with vascular invasion, tumor size could exhibit a notable impact on prognosis 7 . While, for HCC without vascular invasion, tumor size has no significant impact on prognosis 8 . Therefore, tumor biology should be incorporated into the staging classification system for solitary HCC. Recently, Forner A et al. identified that the presence of microvascular invasion and/or satellite lesions (mVI/S) was associated with aggressive recurrence and mortality of early-stage HCC patients 9 . The mVI/S burden configured a notable hallmark of advanced disease and could be used to evaluate the tumor biology of HCC. The incorporation of mVI/S was expected to enhance prognostic restratification in SLHCC. In recent year, postoperative adjuvant therapy attracted much attention for HCC patients at high risk of recurrence. From STORM study to IMbrave050 study, adjuvant systemic therapy failed to improve long-term survival of HCC patient after surgery 10 , 11 . Meanwhile, for HCC patients with MVI, local therapy such as postoperative adjuvant hepatic arterial infusion chemotherapy (HAIC) did not gain OS advantage 12 . Adjuvant transarterial chemoembolization (TACE) appeared to improve prognosis of HCC patient with intermediate or high risk of recurrence, but not for patients with early-stage HCC 13 , 14 . However, contrasting results were observed regarding adjuvant therapy, which showed no survival benefit 15 . Currently, there is no global consensus on recommending adjuvant therapies for HCC patients at high risk of recurrence after surgery. Implementing risk stratification might aid to improve the survival outcomes of postoperative adjuvant TACE 16 . Since management of SLHCC was challenged by narrow surgical margin and high rate of unfavorable pathological features, we conducted a multi-center retrospective study to explored the impact of adjuvant TACE on prognosis of SLHCC. Materials and Methods Study Population Between January 2010 and December 2020, 1292 eligible SLHCC patients who underwent hepatectomy were collected from maintained database in Division of Liver Surgery in West China Hospital, Sichuan Provincial People's Hospital and Chengdu University Affiliated Hospital. The patient selection process was schematically outlined in Figure S1 . Liver surgery was performed by experienced surgeons. The following data were retrospective collected after operation: demographics; routine blood tests, liver function tests, the status of HBV infection, international normalized ratio (INR), total bilirubin (TBIL), alanine aminotransferase (ALT), aspartate aminotransferase (AST), alpha-fetoprotein (AFP) level, liver cirrhosis, tumor size, tumor differentiation; microvascular invasion (MVI), satellite lesion and postoperative adjuvant TACE. Our inclusion criteria were as follows: (1) pathologically proven HCC; (2) initial hepatectomy; (3) Child–Pugh grade A, or Child-Pugh B could be improved A; (4) single tumor with tumor size > 5cm identified by preoperative enhanced CT or MRI. Exclusion criteria: (1) concurrent malignant; (2) major vascular invasion; (3) lymph node involvement; (4) positive surgical margin; (5) tumor invading local organ; (6) tumor rupture; (7) preoperative treatment; (8) incomplete clinicopathological information or follow up data. This study was approved by the ethic committee of West China Hospital, and written informed consent forms were obtained from all the participants. All treatments were performed in accordance with relevant guidelines and regulations. Definitions Satellite lesion was defined as microscopic nodules of HCC separated from the main tumor, which commonly located within 2 cm of the main tumor. One HCC around with satellite nodules was classified into solitary HCC 17 . The presence of MVI was defined as tumor emboli in the hepatic veins, portal vein and lymphatic ducts under microscope. The presence of MVI and satellite lesion was confirmed by hepatic pathologists (Changli Lu and Qing Tao). Ishak score 5 or 6 were defined as liver cirrhosis. SLHCC patients with mVI/S burden was defined as aggressive SLHCC, while those without mVI/S burden was defined as non-aggressive SLHCC. Postoperative adjuvant TACE implementation At postoperative 4 to 6 weeks, when liver function has recovered, patients should undergo screening CT or MRI to confirm a complete radiological response. This confirmation must be made collaboratively by experienced radiologists and interventional radiologists. Only patients with no residual tumor in the remnant liver are defined as candidates for prophylactic treatment. Patients receiving TACE for radiologically confirmed recurrence are classified into the treatment group. The TACE procedure is performed as follows: Using the Seldinger technique, an angiographic catheter is inserted via the femoral artery to access the hepatic artery. Angiography of the common hepatic artery and superior mesenteric artery is then performed to delineate the true hepatic arterial anatomy and confirm portal vein patency. Superselective catheterization of the right and left hepatic arteries is achieved using a microcatheter, followed by injection of epirubicin (10–50 mg) mixed with lipiodol (3–5 ml). The specific chemotherapeutic agents and dosages were determined by the treating physician based on the patient's body surface area, remnant liver volume, and overall health status. Follow-up protocol All patients were followed up at the first, third and sixth months in the first half year after the operation, every 3 months throughout the following 3 years, and every 6 months thereafter after surgery. At each of the follow-up visits, routine blood tests, liver function tests, serum AFP levels, HBV-DNA, and radiological examinations (ultrasound, contrast-enhanced ultrasound, contrast-enhanced computed tomography, or magnetic resonance imaging (MRI)) were performed. Antiviral drugs were administered to patients with positive HBV-DNA load before and after operation. Postoperative recurrence was defined as two typical imaging findings or one and increased AFP levels or confirmed by biopsy/resection. Treatment methods including repeat surgery, radiofrequency ablation (RFA), TACE, systemic treatment and best supportive care for recurrent HCC were recommended based on recurrence pattern and functional liver reserve. Overall survival (OS) time was described as the interval between the operation and death or the last follow up. Recurrence free survival (RFS) time was defined as the time interval between the operation and the first incidence of detectable recurrence. The final follow-up visit occurred at the end of 2024, or until death. The median follow-up time was 51 months. Statistical analysis Continuous variables are expressed as means ± standard deviations and were compared using the t-test (or Mann-Whitney U test for variables with an abnormal distribution). Categorical data were present as the number of cases and the prevalence and were compared using the χ2 test or Fisher's exact test. Univariate and multivariate analysis was performed using the Cox proportional hazards model. Potential risk factors with p < 0.05 in the univariate analysis would enter into the Cox model. Survival analysis was performed using the Kaplan–Meier method, and was compared using the log-rank test. To mitigate the potential impact of confounding variables, we utilized the Inverse Probability of Treatment Weighting (IPTW) method. It involved assigning distinct weights to the two patient cohorts based on their propensity scores - specifically applying the inverse propensity score to one cohort and the reciprocal of (1-propensity score) to the other. A standardized mean difference below 0.1 for any co-variate was considered indicative of adequate balance between the groups. Results Clinicopathological characteristics A total of 1292 patients were included in this study. The detailed screening process is shown in Figure S1 . The clinicopathological characteristics of the whole cohort are shown in Table 1 . Of the all patients, there were 420 patients (32.5%) with age > 60 y and 1103 male patients (85.4%). The rate of positive HBsAg and positive HBeAg were 78.8% and 16.1%, respectively. 40 patients (3.1%) had elevated TBIL (median:13.3µmol/L). 565 patients (43.7%) had elevated ALT (median:37U/L). 404 patients (31.3%) had decreased serum ALB level (median:42.2g/L). 240 patients (18.6%) had thrombocytopenia (median:154×10^9/L). Pathological assessment confirmed 545 patients (42.2%) had pathologically liver cirrhosis. Serum AFP above 400ng/mL was observed in 519 (40.2%) patients. 524 patients (40.6%) had poorly differentiated tumor. Among SLHCC patients, the presence of mVI/S burden reached up to 44.2%. SLHCC patients with mVI/S had higher rate of HBV infection and active HBV replication. About tumor characteristic, the rate of patients with AFP above 400ng/mL, capsular invasion and poorly differentiated tumor was significantly higher than that of SLHCC patient without mVI/S. Meanwhile, tumor size was larger in patients with mVI/S. SLHCC patient without mVI/S had lower serum AST level and higher PLT count (Table 1 ). Table 1 Baseline characteristics of the patient and stratified by mVI/S burden Variable all without mVI/S with mVI/S p value n = 1292 n = 721 n = 571 Age (> 60y) 420 (32.5) 261 (36.2) 159 (27.8) 0.002 Gender(male) 1103 (85.4) 605 (83.9) 498 (87.2) 0.112 HBsAg 1018 (78.8) 554 (76.8) 464 (81.3) 0.062 HBeAg 208 (16.1) 103 (14.3) 105 (18.4) 0.055 HBcAb 1237 (95.7) 682 (94.6) 555 (97.2) 0.030 TBIL(> 28µmol/L) 40 (3.1) 20 (2.8) 20 (3.5) 0.556 TBIL(µmol/L) 13.3 (10.1, 17.5) 13.1 (9.8, 17.5) 13.4 (10.4, 17.5) 0.228 ALT(> 40U/L) 565 (43.7) 310 (43.0) 255 (44.7) 0.588 ALT (U/L) 37 (26, 57) 36(25, 56) 37 (27, 57) 0.157 AST(> 40U/L) 639 (49.5) 321 (44.5) 318 (55.7) < 0.001 AST (U/L) 40 (30, 59) 38 (28, 55) 44 (32, 65) < 0.001 ALB( 6.1mmol/L) 208 (16.1) 123 (17.1) 85 (14.9) 0.327 PLT(> 100*10^9/L) 240 (18.6) 135 (18.7) 105 (18.4) 0.935 PLT (10^9/L) 154 (111, 204) 147 (108, 201) 163 (114, 206) 0.010 Neutrophil (10^9/L) 3.39 (2.66, 4.38) 3.37 (2.59, 4.32) 3.43 (2.70, 4.40) 0.140 Lymphocyte (10^9/L) 1.44 (1.14, 1.80) 1.45 (1.15, 1.83) 1.44 (1.12, 1.77) 0.083 Crea (µmol/L) 72.1 (64.0, 83.0) 72.1 (64.0, 83.6) 72.6 (64.0, 82.0) 0.868 NLR* 646 (50.0) 353 (49.0) 293 (51.3) 0.433 PLR* 646 (50.0) 324 (44.9) 322 (56.4) < 0.001 Liver cirrhosis 545 (42.2) 295 (40.9) 250 (43.8) 0.327 Tumor size(cm) 7.5 (6.0, 10.0) 7.0 (6.0, 9.0) 8.0 (6.5, 10.8) < 0.001 Capsular invasion 740 (57.3) 378 (52.4) 362 (63.4) < 0.001 Poorly differentiated Tumor 524 (40.6) 262 (36.3) 262 (45.9) 0.001 MVI 498 (38.5) 0 (0.0) 498 (87.2) < 0.001 Satellite lesion 146 (11.3) 0 (0.0) 146 (25.6) 400ng/mL) 519 (40.2) 247 (34.3) 272 (47.6) < 0.001 Postoperative adjuvant TACE 353(27.3) 137(19) 216(31.8) < 0.001 TBIL: total bilirubin, ALT: alanine aminotransferase, AST: aspartate aminotransferase, GLU: blood glucose level, ALB: albumin, PLT: platelet, PLR: platelet-to-lymphocyte ratio, NLR: neutrophil-to-lymphocyte ratio, MVI: microvascular invasion, AFP: alpha-fetoprotein * graded by median value The mVI/S burden re-stratified SLHCC Survival analysis demonstrated that the 1, 3, 5, 10-year of RFS were 70.5%, 50.8%, 38.6% and 20.1%, respectively, for SLHCC patients, and the 1, 3, 5, 10-year of OS were 88.2%, 67.7%, 56% and 39.4%, respectively, respectively, for SLHCC patients ( Figure S2 ). In subgroup analysis, the 1, 3, 5, 10-year of RFS were 79.3%, 60.1%, 46.2% and 24.6%, respectively for non-aggressive SLHCC patients, and 59.4%, 39.1%, 28.7% and 13.8%, respectively, for aggressive SLHCC patients ( p < 0.001, Fig. 1 a). The 1, 3, 5, 10-year of OS were 92.0%, 76.1%, 65.4% and 51.7%, respectively, for non-aggressive SLHCC patients, and 83.5%, 57.1%, 44.9% and 21.2%, respectively, for aggressive SLHCC patients ( p < 0.001, Fig. 1 b). Non-aggressive SLHCC patients had significant better prognosis than that of aggressive SLHCC patients. The role of postoperative adjuvant TACE in SLHCC 216 (31.8%) patients received postoperative adjuvant TACE in aggressive group, while in non-aggressive group, 137 (19%) patients received postoperative adjuvant TACE. Survival analysis demonstrated that the 1, 3, 5, 10-year of RFS were 78.5%, 57.7%, 43.8% and 20.5%, respectively for SLHCC patients with postoperative adjuvant TACE, and 67.5%, 48.2%, 36.7% and 20.1%, respectively, for SLHCC patients without postoperative adjuvant TACE ( p < 0.001, Figure S3 ). The 1, 3, 5, 10-year of OS were 93.8%, 69.6%, 56.8% and 36.9%, respectively for SLHCC patients with postoperative adjuvant TACE, and 86.1%, 67%, 55.6% and 39.9%, respectively, for SLHCC patients without postoperative adjuvant TACE (p = 0.72, Figure S3 ). Among patients with non-aggressive SLHCC, the 1, 3, 5, 10-year of RFS were 93.4%, 75%, 56.8% and 25.3%, respectively for patients with postoperative adjuvant TACE, and 76%, 56.6%,43.7% and 24.8%, respectively, for patients without postoperative adjuvant TACE ( p = 0.043, Fig. 2 a). After adjusting tumor size, tumor differentiation, capsular invasion, AFP, HBsAg, HBeAg, liver cirrhosis, elevated ALT and elevated AST, this difference in term of RFS was consistent in the IPTW analyses ( p = 0.018, Fig. 2 c). The 1, 3, 5, 10-year of OS were 98.5%, 81.7%, 64.9% and 50.9%, respectively, for patients with postoperative adjuvant TACE, and 90.4%, 74.7%,64.3% and 51.8%, respectively, for patients without postoperative adjuvant TACE ( p = 0.52, Fig. 2 b). The IPTW analyses confirmed the results ( p = 0.249, Fig. 2 d). Among patients with aggressive SLHCC subgroup, the 1, 3, 5, 10-year of RFS were 69%, 46.7%, 35.6% and 18.1%, respectively for patients with postoperative adjuvant TACE, and 53.5%, 34.4%, 24.5% and 11.4%, respectively, for patients without postoperative adjuvant TACE ( p < 0.001, Fig. 3 a). The 1, 3, 5, 10-year of OS were 90.7%,61.9%, 52.4% and 25.5%, respectively, for patients with postoperative adjuvant TACE, and 79.1%, 54.2%,40.9% and 19.2%, respectively, for patients without postoperative adjuvant TACE ( p = 0.033, Fig. 3 b). After adjusting tumor size, tumor differentiation, capsular invasion, AFP, HBsAg, HBeAg, liver cirrhosis, elevated ALT and elevated AST, this difference in term of RFS and OS were consistent in the IPTW analyses (RFS: p < 0.001, Fig. 3 c; OS: p = 0.029, Fig. 3 d). Prognostic factors for SLHCC patients As shown in Table 2 . Multivariate analyses revealed that the following factors were associated with RFS: tumor size (HR:1.07), capsular invasion (HR:1.20), mIV/S (HR:1.53), HBsAg (HR:1.32), HBeAg (HR:1.31), postoperative adjuvant TACE (HR:0.73), liver cirrhosis (HR:1.20), tumor differentiation (HR:1.31) and elevated AST (HR:1.26). Similarly, multivariate analysis identified that tumor size (HR:1.07), capsular invasion (HR:1.49), mIV/S (HR:1.79), HBeAg (HR:1.30), AFP above 400ng/mL (HR:1.19), liver cirrhosis (HR:1.33), elevated ALT (HR:1.22) were predictors of OS (Table 3 ). Subgroup analysis using Cox multivariate regression revealed that postoperative adjuvant TACE was associated with RFS (HR: 0.74,95%CI:0.58–0.93, p = 0.011), but not OS (HR:0.91 95%CI:0.68–1.22, p = 0.523) in non-aggressive SLHCC, and was associated with RFS (HR:0.68,95%CI:0.53–0.87, p < 0.001) and OS (HR:0.72 95%CI:0.57–0.91, p = 0.007) in aggressive SLHCC ( Table S1 and Table S2 ). Table 2 Predictive factors for recurrence free survival after hepatectomy Univariate analysis Multivariate analysis Variable HR 95%CI p value HR 95%CI p value Age (> 60 y) 0.69 0.60–0.81 < 0.001 0.87 0.75–1.04 0.116 Gender (male vs female) 1.11 0.91–1.36 0.299 HBsAg 1.66 1.38-2.00 < 0.001 1.32 1.06–1.64 0.012 HBeAg 1.65 1.39–1.96 28µmol/L) 1.03 0.69–1.54 0.868 ALT(> 40U/L) 1.28 1.12–1.47 40U/L) 1.57 1.37–1.80 < 0.001 1.26 1.06–1.51 0.01 ALB( 6.1mmol/L) 0.86 0.70–1.04 0.117 NLR 1.06 0.92–1.22 0.398 PLR 1.10 0.96–1.26 0.186 AFP(> 400ng/mL) 1.32 1.15–1.51 < 0.001 1.11 0.96–1.29 0.147 Liver cirrhosis 1.29 1.12–1.48 < 0.001 1.20 1.04–1.51 0.013 Tumor size 1.07 1.05–1.10 < 0.001 1.04 1.02–1.07 0.002 mIV/S 1.74 1.51–1.99 < 0.001 1.53 1.32–1.76 < 0.001 Capsular invasion 1.35 1.17–1.56 < 0.001 1.20 1.03–1.38 0.016 Poorly differentiated tumor 1.26 1.10–1.45 0.001 1.31 1.09–1.57 0.004 Postoperative adjuvant TACE 0.84 0.73–0.98 0.023 0.73 0.63–0.85 < 0.001 HR:hazard ratio; TBIL: total bilirubin, ALT: alanine aminotransferase, AST: aspartate aminotransferase, GLU: blood glucose level, ALB: albumin, PLT: platelet, PLR: platelet-to-lymphocyte ratio, NLR: neutrophil-to-lymphocyte ratio, MVI: microvascular invasion, AFP: alpha-fetoprotein;TACE:transhepatic arterial chem otherapy and embolization. Table 3 Predictive factors for overall survival after hepatectomy Univariate analysis Multivariate analysis HR 95%CI p value HR 95%CI p value Age (> 60 y) 0.85 0.72–1.01 0.065 1.08 0.89–1.30 0.44 Gender (male vs female) 1.14 0.91–1.43 0.266 HBsAg 1.50 1.22–1.85 < 0.001 1.18 0.94–1.48 0.15 HBeAg 1.60 1.31–1.94 28µmol/L) 0.96 0.60–1.53 0.849 ALT(> 40U/L) 1.38 1.18–1.61 40U/L) 1.61 1.37–1.89 < 0.001 1.16 0.95–1.42 0.146 ALB(( 6.1mmol/L) 0.89 0.72–1.11 0.318 NLR 1.24 1.06–1.46 0.006 1.18 0.99–1.40 0.06 PLR 1.17 1.00-1.37 0.054 0.93 0.78–1.11 0.403 AFP(> 400ng/mL) 1.40 1.20–1.65 < 0.001 1.19 1.02–1.41 0.033 Liver cirrhosis 1.35 1.15–1.57 < 0.001 1.33 1.13–1.56 0.001 Tumor size 1.09 1.07–1.12 < 0.001 1.07 1.04–1.09 < 0.001 mIV/S 1.90 1.62–2.23 < 0.001 1.79 1.52–2.11 < 0.001 Capsular invasion 1.64 1.39–1.94 < 0.001 1.49 1.26–1.76 < 0.001 Poorly differentiated tumor 1.43 1.22–1.67 < 0.001 1.16 0.99–1.30 0.065 Postoperative adjuvant TACE 0.98 0.83–1.17 0.843 HR:hazard ratio; TBIL: total bilirubin, ALT: alanine aminotransferase, AST: aspartate aminotransferase, GLU: blood glucose level, ALB: albumin, PLT: platelet, PLR: platelet-to-lymphocyte ratio, NLR: neutrophil-to-lymphocyte ratio, MVI: microvascular invasion, AFP: alpha-fetoprotein;TACE:transhepatic arterial chem otherapy and embolization. Discussion SLHCC was a subgroup of solitary HCC. In current study, we included relatively large sample of SLHCC with long-term follow-up. The overall 5- and 10-year survival was 56% and 39.4%, which was significantly worse than that of patient with early-stage HCC 18 . Therefore, we contended that simply classifying SLHCC as early-stage HCC might be inappropriate. The presence of MVI in HCC was well-established predictor of tumor biology, which indicated a potential tumor disseminate and had negative impact on HCC prognosis after hepatectomy or liver transplantation 19 . Among 1292 SLHCC patients, the rate of MVI was 38.5%. Satellite lesion was significantly associated with poorly differentiated HCC, indicating potential tumor disseminate 20 . The rate of satellite lesion was 11.3% in SLHCC patients.73 SLHCC patients (5.6%) had both MVI and satellite lesion. Satellite lesions and MVI could significantly modify survival probabilities of HCC patients 9 . In current study, we further classified SLHCC into aggressive SLHCC and non-aggressive SLHCC based on the status of mVI/S burden. As result of our data analysis, patient with aggressive SLHCC had more unfavorable tumor characteristics, such as elevated AFP, capsular invasion and poorly differentiated HCC. Based on the survival analysis, patients with non-aggressive SLHCC had significantly better long-term survival than those with aggressive SLHCC, showing the 5 and 10-year survival rate of only 44.9% and 31.2%, respectively. The prognosis of non-aggressive SLHCC patients was comparable to that of patents within early-stage HCC 21 , while the prognosis of aggressive SLHCC patients was significantly inferior. Tumor biology was the fundamental factor that determined the prognosis of HCC patients 9 . How to select proper indicator for tumor biology was critical. Despite numerous gene signature was explored to reflect tumor aggressiveness, it was limited for its expensive and ineffective 20 . Tumor characteristics detected by microscope remained to be mainstay to designate tumor biology. In current study, we selected the status of mVI/S to determine the aggressivity of HCC. The presence of mVI/S was identified to be the only independent risk factor for aggressive recurrence and mortality in single HCC 9 . Unlike the growth of cholangiocarcinoma, HCC commonly enlarged with expansive growth. From the surgery standpoint, complete remove of tumor might be technically feasible. However, clinical implementation is often constrained by two key factors: (1) HCC commonly occurred with underlying liver fibrosis, and (2) patients with large HCC hardly achieved wide surgical margin, particularly when tumors are adjacent to critical vascular structures. The presence of mVI/S increased risk of recurrence. For those with non-aggressive SLHCC, surgical resection tended to achieve radical remove of tumor. Tumor size was hotly debated for its role in patient survival. Kokudo et al 20 identified that tumor size was not a prognostic factor. Solitary HCC > 10cm would be a good candidate for hepatectomy as well as solitary HCC between 5 and 10cm 20 . Our study suggested that among patients with SLHCC, tumor size had negative effects on the prognosis in term of RFS and OS. This phenomenon might be attributable to the association between increasing tumor size and established adverse prognostic indicators, including vascular invasion status and histologic differentiation grade. Capsular invasion, AFP above 400ng/mL and poorly tumor differentiation was identified as risk factors for SLHCC patients. Among SLHCC patients, over 50% of patients had capsular invasion; and 40.2% had AFP > 400ng/mL, and 40.6% had poorly tumor differentiation. Particularly, aggressive SLHCC had higher rate of these above-mentioned tumor characteristics. On the other hand, liver cirrhosis and status of HBV was significantly associated with prognosis of SLHCC patients. In China, the majority of HCC occurred in hepatitis B and liver cirrhosis. Despite surgery could completely remove the tumor, underlying liver disease and viral replication had been validated to contribute to tumor recurrence 22 . Active antiviral therapy aided to reduce the rate of tumor recurrence and prolong long-term survival 23 . Adjuvant TACE was expected to improve prognosis of HCC patients at high risk of recurrence. Zhou et al. 13 reported that adjuvant TACE improved outcomes in HBV-related HCC patients with intermediate or high recurrence risk post-hepatectomy, demonstrating a 12.9% increase in RFS and a 7.8% higher 3-year OS rate. Cheng et al suggested adjuvant TACE was associated with a lower risk of death among advanced HCC 14 . In our study, we found that adjuvant TACE improved prognosis of aggressive SLHCC, but not for non-aggressive SLHCC. Non-aggressive SLHCC patients seemed to gain less long-term survival benefits from adjuvant TACE. This might be due to relative benign tumor characteristics for non-aggressive SLHCC. Supporting our findings, adjuvant TACE rarely improve prognosis of American Joint Committee on Cancer TNM stage I or II HCC 24 . Patients with high risk of recurrence benefited from adjuvant TACE 16 . For aggressive SLHCC patients, they were at high risk of potential tumor dissemination. Adjuvant TACE could treat any pre-existing microscopic tumor foci or occult intrahepatic multifocality, improving the prognosis of HCC patients with highly aggressive tumors 25 . Our results also demonstrated effectiveness in the adjuvant setting for patients with aggressive SLHCC. Consistently, Cheng et al. demonstrating that adjuvant TACE was beneficial for be beneficial for HCC patients with MVI 26 . There are some limitations in this study. First, this is a retrospective. We adopted multicenter data to overcome the section bias. Secondly, the majority of HCC patients in the current study had history of hepatitis B virus infection, which was different from the Western countries (predominantly hepatitis C virus infection). Thirdly, some date such as HBV-DNA was completely recorded, in current study, we did not include them to further analyze. However, all the antiviral regimen for HBV treatment was recommended based on guideline and patients received regular follow-up after surgery. In conclusion, our findings demonstrated that mVI/S status effectively stratified SLHCC into distinct prognostic subgroups: non-aggressive and aggressive variants. Notably, non-aggressive SLHCC patients exhibited favorable outcomes comparable to early-stage HCC. Adjuvant TACE significantly improved both RFS and OS in aggressive SLHCC, its prophylactic benefit appeared limited in non-aggressive cases, showing only marginal RFS improvement without significant OS advantage. Declarations Conflict of interest None Ethic statement The protocol for this research project was approved by Ethics Committee of west China hospital, and written informed consent was obtained from all patients. This study conformed to the provisions of the Declaration of Helsinki. Funding This study was supported by the Natural Science Foundation of Sichuan Province (No. 2025ZNSFSC1920), and the "Qimingxing" Research Fund for Young Talents of West China Hospital (No. HXQMX0062), and the West China Hospital Incubation Project (No. 22HXFH011). Author Contribution Chuwen Chen: Conceptualization, Data curation, Formal analysis, Investigation, Methodology, Writing original draft,Writing review & editing.Qing Tao: Investigation, Resources, Software, Validation, Visualization.Changli Lu: Data curation, Project administration, Supervision, Validation.Yu Zhang: Formal analysis, Methodology, Resources, Software.Shusheng Leng: Data curation, Supervision.Tianfu Wen: Conceptualization, Supervision, Writing – review & editing.Junyi Shen: Methodology, Project administration, Supervision, Validation, Writing – review & editing. Acknowledgement NO Data Availability The data that support the findings of this study are available from the corresponding author upon request. References Wang FS, Fan JG, Zhang Z, Gao B, Wang HY. The global burden of liver disease: the major impact of China. Hepatology. 2014;60(6):2099–108. Xiang L, Li J, Chen J, et al. Prospective cohort study of laparoscopic and open hepatectomy for hepatocellular carcinoma. Br J Surg. 2016;103(13):1895–901. Amin MB, Greene FL, Edge SB, et al. The Eighth Edition AJCC Cancer Staging Manual: Continuing to build a bridge from a population-based to a more personalized approach to cancer staging. CA Cancer J Clin. 2017;67(2):93–9. Zhou J, Sun H, Wang Z, et al. Guidelines for the Diagnosis and Treatment of Primary Liver Cancer (2022 Edition). Liver cancer. 2023;12(5):405–44. Yang LY, Fang F, Ou DP, Wu W, Zeng ZJ, Wu F. Solitary large hepatocellular carcinoma: a specific subtype of hepatocellular carcinoma with good outcome after hepatic resection. Ann Surg. 2009;249(1):118–23. Kluger MD, Salceda JA, Laurent A, et al. Liver resection for hepatocellular carcinoma in 313 Western patients: tumor biology and underlying liver rather than tumor size drive prognosis. J Hepatol. 2015;62(5):1131–40. Yang A, Xiao W, Chen D, et al. The power of tumor sizes in predicting the survival of solitary hepatocellular carcinoma patients. Cancer Med. 2018;7(12):6040–50. Goh BK, Teo JY, Chan CY, et al. Importance of tumor size as a prognostic factor after partial liver resection for solitary hepatocellular carcinoma: Implications on the current AJCC staging system. J Surg Oncol. 2016;113(1):89–93. Fuster-Anglada C, Mauro E, Ferrer-Fàbrega J, et al. Histological predictors of aggressive recurrence of hepatocellular carcinoma after liver resection. J Hepatol. 2024;81(6):995–1004. Bruix J, Takayama T, Mazzaferro V, et al. Adjuvant sorafenib for hepatocellular carcinoma after resection or ablation (STORM): a phase 3, randomised, double-blind, placebo-controlled trial. Lancet Oncol. 2015;16(13):1344–54. Qin S, Chen M, Cheng AL, et al. Atezolizumab plus bevacizumab versus active surveillance in patients with resected or ablated high-risk hepatocellular carcinoma (IMbrave050): a randomised, open-label, multicentre, phase 3 trial. Lancet (London England). 2023;402(10415):1835–47. Li SH, Mei J, Cheng Y, et al. Postoperative Adjuvant Hepatic Arterial Infusion Chemotherapy With FOLFOX in Hepatocellular Carcinoma With Microvascular Invasion: A Multicenter, Phase III, Randomized Study. J Clin oncology: official J Am Soc Clin Oncol. 2023;41(10):1898–908. Wang Z, Ren Z, Chen Y, et al. Adjuvant Transarterial Chemoembolization for HBV-Related Hepatocellular Carcinoma After Resection: A Randomized Controlled Study. Clin cancer research: official J Am Association Cancer Res. 2018;24(9):2074–81. Liu S, Guo L, Li H, et al. Postoperative Adjuvant Trans-Arterial Chemoembolization for Patients with Hepatocellular Carcinoma and Portal Vein Tumor Thrombus. Ann Surg Oncol. 2018;25(7):2098–104. An C, Kim DW, Park YN, Chung YE, Rhee H, Kim MJ. Single Hepatocellular Carcinoma: Preoperative MR Imaging to Predict Early Recurrence after Curative Resection. Radiology. 2015;276(2):433–43. Zeng JS, Zeng JX, Huang Y, Liu JF, Zeng JH. The effect of adjuvant transarterial chemoembolization for hepatocellular carcinoma after liver resection based on risk stratification. Hepatobiliary Pancreat Dis international: HBPD INT. 2023;22(5):482–9. Ma T, Bai X, Zhang Q et al. Adjuvant transarterial chemoembolization for hepatocellular carcinoma following curative resection: A randomized, open-label, phase 3 trial. Hepatology (Baltimore MD). 2025. Su JY, Huang DJ, Liu SP et al. Adjuvant Transarterial Chemoembolization After Truly Curative Resection Does Not Improve Survival of Patients With Hepatocellular Carcinoma at High Risk of Recurrence: A Target Trial Emulation Study. Hepatol research: official J Japan Soc Hepatol. 2025. Wang JH, Wang CC, Hung CH, Chen CL, Lu SN. Survival comparison between surgical resection and radiofrequency ablation for patients in BCLC very early/early stage hepatocellular carcinoma. J Hepatol. 2012;56(2):412–8. Lim C, Mise Y, Sakamoto Y, et al. Above 5 cm, size does not matter anymore in patients with hepatocellular carcinoma. World J Surg. 2014;38(11):2910–8. Lee S, Kang TW, Song KD, et al. Effect of Microvascular Invasion Risk on Early Recurrence of Hepatocellular Carcinoma After Surgery and Radiofrequency Ablation. Ann Surg. 2021;273(3):564–71. Shen J, Dai J, Zhang Y, et al. Baseline HBV-DNA load plus AST/ALT ratio predicts prognosis of HBV-related hepatocellular carcinoma after hepatectomy: A multicentre study. J Viral Hepatitis. 2021;28(11):1587–96. Shen J, Qi W, Dai J, et al. Tenofovir vs. entecavir on recurrence of hepatitis B virus-related hepatocellular carcinoma beyond Milan criteria after hepatectomy. Chin Med J. 2021;135(3):301–8. Panettieri E, Campisi A, De Rose AM et al. Emerging Prognostic Markers in Patients Undergoing Liver Resection for Hepatocellular Carcinoma: A Narrative Review. Cancers 2024;16(12). Aufhauser DD Jr., Sadot E, Murken DR, et al. Incidence of Occult Intrahepatic Metastasis in Hepatocellular Carcinoma Treated With Transplantation Corresponds to Early Recurrence Rates After Partial Hepatectomy. Ann Surg. 2018;267(5):922–8. Sun JJ, Wang K, Zhang CZ, et al. Postoperative Adjuvant Transcatheter Arterial Chemoembolization After R0 Hepatectomy Improves Outcomes of Patients Who have Hepatocellular Carcinoma with Microvascular Invasion. Ann Surg Oncol. 2016;23(4):1344–51. Additional Declarations No competing interests reported. Supplementary Files Supplementaryfigures.docx Cite Share Download PDF Status: Under Review Version 1 posted Reviewers invited by journal 30 Oct, 2025 Editor invited by journal 09 Oct, 2025 Editor assigned by journal 07 Oct, 2025 Submission checks completed at journal 07 Oct, 2025 First submitted to journal 06 Oct, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. 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16:38:47","extension":"html","order_by":16,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":175530,"visible":true,"origin":"","legend":"","description":"","filename":"earlyproof.html","url":"https://assets-eu.researchsquare.com/files/rs-7792877/v1/694aaa2a93368067401a9b31.html"},{"id":95663588,"identity":"5ec9b563-ed20-40c2-b305-3d4a7c1d5063","added_by":"auto","created_at":"2025-11-11 16:39:07","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":400669,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003ePatients with non-aggressive SLHCC showed significantly better prognosis than those with aggressive SLHCC.\u003c/strong\u003e \u003cstrong\u003e(a)\u003c/strong\u003e RFS curves: Non-aggressive SLHCC (red) exhibited superior RFS compared to aggressive SLHCC (cyan). SLHCC patients with satellite lesions (dark grey) had poorer RFS than those with MVI (light grey). \u003cstrong\u003e(b)\u003c/strong\u003e OS curves: Non-aggressive SLHCC (red) demonstrated longer OS than aggressive SLHCC (cyan). Patients with satellite lesions (dark grey) showed worse OS than those with MVI (light grey). RFS: recurrence-free survival OS: Overall survival\u003c/p\u003e","description":"","filename":"floatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-7792877/v1/7b17cc765173b71e56dbcce0.png"},{"id":95663317,"identity":"613cdf23-7854-4bf6-a3ec-2aa17ebf7bc2","added_by":"auto","created_at":"2025-11-11 16:38:41","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":158049,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eAdjuvant TACE significantly improved RFS compared to non-adjuvant treatment in non-aggressive SLHCC patients.\u003c/strong\u003e \u003cstrong\u003e(a)\u003c/strong\u003eRFS curves for patients receiving postoperative adjuvant TACE (cyan) versus no adjuvant TACE (red). \u003cstrong\u003e(b)\u003c/strong\u003eOS curves for patients receiving postoperative adjuvant TACE (cyan) versus no adjuvant TACE (red). \u003cstrong\u003e(c) \u003c/strong\u003eRFS curves after IPTW adjustment for patients receiving adjuvant TACE (cyan) versus no adjuvant TACE (red). (\u003cstrong\u003ed)\u003c/strong\u003e OS curves after IPTW adjustment for patients receiving adjuvant TACE (cyan) versus no adjuvant TACE (red). IPTW, inverse probability of treatment weights.\u003c/p\u003e","description":"","filename":"floatimage2.png","url":"https://assets-eu.researchsquare.com/files/rs-7792877/v1/84fce0e27221abef53d211e6.png"},{"id":95663478,"identity":"abd811c3-c996-4cc6-8c1e-fb94e1e3fa67","added_by":"auto","created_at":"2025-11-11 16:38:58","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":149898,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003ePostoperative adjuvant TACE was associated with significantly improved outcomes in aggressive SLHCC compared to non-adjuvant treatment. (a)\u003c/strong\u003e RFS in aggressive SLHCC: adjuvant TACE (cyan) vs. non-adjuvant (red). \u003cstrong\u003e(b)\u003c/strong\u003e OS in aggressive SLHCC: adjuvant TACE (cyan) vs. non-adjuvant (red). \u003cstrong\u003e(c)\u003c/strong\u003e RFS after IPTW adjustment: adjuvant TACE (cyan) vs. non-adjuvant (red). \u003cstrong\u003e(d)\u003c/strong\u003e OS after IPTW adjustment: adjuvant TACE (cyan) vs. non-adjuvant (red).\u003c/p\u003e","description":"","filename":"floatimage3.png","url":"https://assets-eu.researchsquare.com/files/rs-7792877/v1/aacb132b53145ce935c2abe3.png"},{"id":95664106,"identity":"f8d15551-bfd2-4475-a9dc-f72230e9ffac","added_by":"auto","created_at":"2025-11-11 16:39:53","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1737563,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7792877/v1/95dbab83-c828-4e6b-b715-b3df91bc80d6.pdf"},{"id":95663501,"identity":"19cdbc83-1710-4091-86ff-9791951a84aa","added_by":"auto","created_at":"2025-11-11 16:39:01","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":289211,"visible":true,"origin":"","legend":"","description":"","filename":"Supplementaryfigures.docx","url":"https://assets-eu.researchsquare.com/files/rs-7792877/v1/fe4e0c2de4e1f2b0a53faf3e.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Adjuvant transarterial chemoembolization for solitary large hepatocellular carcinoma by microvascular invasion and/or satellite lesion burden：A Multi-Center Retrospective Study","fulltext":[{"header":"Highlight","content":"\u003cp\u003e1. Solitary large HCC (SLHCC) should be further classified as non-aggressive SLHCC and aggressive SLHCC based on microvascular invasion and/or satellite lesion (mVI/S) burden. Non-aggressive SLHCC patients had long term survival, comparable to patients with early-stage HCC.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e2. For those with aggressive SLHCC, long-term survival was dismal. Postoperative adjuvant transarterial chemoembolization (TACE) showed benefits in both recurrence free survival (RFS) and overall survival (OS).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e3. Adjuvant TACE could improve RFS in non-aggressive SLHCC patients. However, Adjuvant TACE did not significantly impact OS.\u003c/p\u003e"},{"header":"Introduction","content":"\u003cp\u003eHepatocellular carcinoma (HCC) was one of the most frequent cancers worldwide, with China alone accounting for about 50% of the total number of cases and deaths\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u003c/sup\u003e. Solitary large HCC (\u0026gt;\u0026thinsp;5cm, SLHCC) was a subgroup of HCCs, which caught much attention for its proper position. Current staging systems exhibited significant discordance in classifying SLHCC. Barcelona Clinic Liver Cancer (BCLC) staging system was widely used to evaluate HCC of patients including tumor stage and treatment guidance. BCLC system categorizes SLHCC as early-stage (Stage A)\u003csup\u003e2\u003c/sup\u003e, while the AJCC 8th edition incorporates vascular invasion status to differentiate SLHCC into T1b and T2 classifications, respectively\u003csup\u003e\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u003c/sup\u003e. The CNLC stage system defined SLHCC as Ib stage, which had worse prognosis than that of small HCC\u003csup\u003e\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u003c/sup\u003e. Yang et al \u003csup\u003e5\u003c/sup\u003esuggested that tumor aggressive-related genes seem had no correlation with the tumor size. Tumor biology and underlying liver other than tumor size determined prognosis\u003csup\u003e\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u003c/sup\u003e. Study based on Surveillance Epidemiology and End Results (SEER) database, suggested that for solitary HCC with vascular invasion, tumor size could exhibit a notable impact on prognosis\u003csup\u003e\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u003c/sup\u003e. While, for HCC without vascular invasion, tumor size has no significant impact on prognosis\u003csup\u003e\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u003c/sup\u003e. Therefore, tumor biology should be incorporated into the staging classification system for solitary HCC. Recently, Forner A et al. identified that the presence of microvascular invasion and/or satellite lesions (mVI/S) was associated with aggressive recurrence and mortality of early-stage HCC patients\u003csup\u003e\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u003c/sup\u003e. The mVI/S burden configured a notable hallmark of advanced disease and could be used to evaluate the tumor biology of HCC. The incorporation of mVI/S was expected to enhance prognostic restratification in SLHCC.\u003c/p\u003e\u003cp\u003eIn recent year, postoperative adjuvant therapy attracted much attention for HCC patients at high risk of recurrence. From STORM study to IMbrave050 study, adjuvant systemic therapy failed to improve long-term survival of HCC patient after surgery\u003csup\u003e\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e,\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u003c/sup\u003e. Meanwhile, for HCC patients with MVI, local therapy such as postoperative adjuvant hepatic arterial infusion chemotherapy (HAIC) did not gain OS advantage\u003csup\u003e\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u003c/sup\u003e. Adjuvant transarterial chemoembolization (TACE) appeared to improve prognosis of HCC patient with intermediate or high risk of recurrence, but not for patients with early-stage HCC\u003csup\u003e\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e,\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u003c/sup\u003e. However, contrasting results were observed regarding adjuvant therapy, which showed no survival benefit\u003csup\u003e\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u003c/sup\u003e. Currently, there is no global consensus on recommending adjuvant therapies for HCC patients at high risk of recurrence after surgery. Implementing risk stratification might aid to improve the survival outcomes of postoperative adjuvant TACE\u003csup\u003e\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u003c/sup\u003e. Since management of SLHCC was challenged by narrow surgical margin and high rate of unfavorable pathological features, we conducted a multi-center retrospective study to explored the impact of adjuvant TACE on prognosis of SLHCC.\u003c/p\u003e"},{"header":"Materials and Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003eStudy Population\u003c/h2\u003e\u003cp\u003eBetween January 2010 and December 2020, 1292 eligible SLHCC patients who underwent hepatectomy were collected from maintained database in Division of Liver Surgery in West China Hospital, Sichuan Provincial People's Hospital and Chengdu University Affiliated Hospital. The patient selection process was schematically outlined in \u003cb\u003eFigure S1\u003c/b\u003e. Liver surgery was performed by experienced surgeons. The following data were retrospective collected after operation: demographics; routine blood tests, liver function tests, the status of HBV infection, international normalized ratio (INR), total bilirubin (TBIL), alanine aminotransferase (ALT), aspartate aminotransferase (AST), alpha-fetoprotein (AFP) level, liver cirrhosis, tumor size, tumor differentiation; microvascular invasion (MVI), satellite lesion and postoperative adjuvant TACE. Our inclusion criteria were as follows: (1) pathologically proven HCC; (2) initial hepatectomy; (3) Child\u0026ndash;Pugh grade A, or Child-Pugh B could be improved A; (4) single tumor with tumor size\u0026thinsp;\u0026gt;\u0026thinsp;5cm identified by preoperative enhanced CT or MRI. Exclusion criteria: (1) concurrent malignant; (2) major vascular invasion; (3) lymph node involvement; (4) positive surgical margin; (5) tumor invading local organ; (6) tumor rupture; (7) preoperative treatment; (8) incomplete clinicopathological information or follow up data. This study was approved by the ethic committee of West China Hospital, and written informed consent forms were obtained from all the participants. All treatments were performed in accordance with relevant guidelines and regulations.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003c/div\u003e\n\u003ch3\u003eDefinitions\u003c/h3\u003e\n\u003cp\u003eSatellite lesion was defined as microscopic nodules of HCC separated from the main tumor, which commonly located within 2 cm of the main tumor. One HCC around with satellite nodules was classified into solitary HCC\u003csup\u003e\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u003c/sup\u003e. The presence of MVI was defined as tumor emboli in the hepatic veins, portal vein and lymphatic ducts under microscope. The presence of MVI and satellite lesion was confirmed by hepatic pathologists (Changli Lu and Qing Tao). Ishak score 5 or 6 were defined as liver cirrhosis. SLHCC patients with mVI/S burden was defined as aggressive SLHCC, while those without mVI/S burden was defined as non-aggressive SLHCC.\u003c/p\u003e\n\u003ch3\u003ePostoperative adjuvant TACE implementation\u003c/h3\u003e\n\u003cp\u003eAt postoperative 4 to 6 weeks, when liver function has recovered, patients should undergo screening CT or MRI to confirm a complete radiological response. This confirmation must be made collaboratively by experienced radiologists and interventional radiologists. Only patients with no residual tumor in the remnant liver are defined as candidates for prophylactic treatment. Patients receiving TACE for radiologically confirmed recurrence are classified into the treatment group.\u003c/p\u003e\u003cp\u003eThe TACE procedure is performed as follows: Using the Seldinger technique, an angiographic catheter is inserted via the femoral artery to access the hepatic artery. Angiography of the common hepatic artery and superior mesenteric artery is then performed to delineate the true hepatic arterial anatomy and confirm portal vein patency. Superselective catheterization of the right and left hepatic arteries is achieved using a microcatheter, followed by injection of epirubicin (10\u0026ndash;50 mg) mixed with lipiodol (3\u0026ndash;5 ml). The specific chemotherapeutic agents and dosages were determined by the treating physician based on the patient's body surface area, remnant liver volume, and overall health status.\u003c/p\u003e\n\u003ch3\u003eFollow-up protocol\u003c/h3\u003e\u003cp\u003eAll patients were followed up at the first, third and sixth months in the first half year after the operation, every 3 months throughout the following 3 years, and every 6 months thereafter after surgery. At each of the follow-up visits, routine blood tests, liver function tests, serum AFP levels, HBV-DNA, and radiological examinations (ultrasound, contrast-enhanced ultrasound, contrast-enhanced computed tomography, or magnetic resonance imaging (MRI)) were performed. Antiviral drugs were administered to patients with positive HBV-DNA load before and after operation. Postoperative recurrence was defined as two typical imaging findings or one and increased AFP levels or confirmed by biopsy/resection. Treatment methods including repeat surgery, radiofrequency ablation (RFA), TACE, systemic treatment and best supportive care for recurrent HCC were recommended based on recurrence pattern and functional liver reserve. Overall survival (OS) time was described as the interval between the operation and death or the last follow up. Recurrence free survival (RFS) time was defined as the time interval between the operation and the first incidence of detectable recurrence. The final follow-up visit occurred at the end of 2024, or until death. The median follow-up time was 51 months.\u003c/p\u003e\u003cdiv id=\"Sec7\" class=\"Section2\"\u003e\u003ch2\u003eStatistical analysis\u003c/h2\u003e\u003cp\u003eContinuous variables are expressed as means\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviations and were compared using the t-test (or Mann-Whitney U test for variables with an abnormal distribution). Categorical data were present as the number of cases and the prevalence and were compared using the χ2 test or Fisher's exact test. Univariate and multivariate analysis was performed using the Cox proportional hazards model. Potential risk factors with p\u0026thinsp;\u0026lt;\u0026thinsp;0.05 in the univariate analysis would enter into the Cox model. Survival analysis was performed using the Kaplan\u0026ndash;Meier method, and was compared using the log-rank test. To mitigate the potential impact of confounding variables, we utilized the Inverse Probability of Treatment Weighting (IPTW) method. It involved assigning distinct weights to the two patient cohorts based on their propensity scores - specifically applying the inverse propensity score to one cohort and the reciprocal of (1-propensity score) to the other. A standardized mean difference below 0.1 for any co-variate was considered indicative of adequate balance between the groups.\u003c/p\u003e\u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec9\" class=\"Section2\"\u003e\u003ch2\u003eClinicopathological characteristics\u003c/h2\u003e\u003cp\u003eA total of 1292 patients were included in this study. The detailed screening process is shown in \u003cb\u003eFigure S1\u003c/b\u003e. The clinicopathological characteristics of the whole cohort are shown in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. Of the all patients, there were 420 patients (32.5%) with age\u0026thinsp;\u0026gt;\u0026thinsp;60 y and 1103 male patients (85.4%). The rate of positive HBsAg and positive HBeAg were 78.8% and 16.1%, respectively. 40 patients (3.1%) had elevated TBIL (median:13.3\u0026micro;mol/L). 565 patients (43.7%) had elevated ALT (median:37U/L). 404 patients (31.3%) had decreased serum ALB level (median:42.2g/L). 240 patients (18.6%) had thrombocytopenia (median:154\u0026times;10^9/L). Pathological assessment confirmed 545 patients (42.2%) had pathologically liver cirrhosis. Serum AFP above 400ng/mL was observed in 519 (40.2%) patients. 524 patients (40.6%) had poorly differentiated tumor. Among SLHCC patients, the presence of mVI/S burden reached up to 44.2%. SLHCC patients with mVI/S had higher rate of HBV infection and active HBV replication. About tumor characteristic, the rate of patients with AFP above 400ng/mL, capsular invasion and poorly differentiated tumor was significantly higher than that of SLHCC patient without mVI/S. Meanwhile, tumor size was larger in patients with mVI/S. SLHCC patient without mVI/S had lower serum AST level and higher PLT count (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eBaseline characteristics of the patient and stratified by mVI/S burden\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"5\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eVariable\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eall\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003ewithout mVI/S\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003ewith mVI/S\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003ep value\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003en\u0026thinsp;=\u0026thinsp;1292\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003en\u0026thinsp;=\u0026thinsp;721\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003en\u0026thinsp;=\u0026thinsp;571\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAge (\u0026gt;\u0026thinsp;60y)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e420 (32.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e261 (36.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e159 (27.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e\u003cb\u003e0.002\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eGender(male)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1103 (85.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e605 (83.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e498 (87.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.112\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHBsAg\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1018 (78.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e554 (76.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e464 (81.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.062\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHBeAg\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e208 (16.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e103 (14.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e105 (18.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.055\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHBcAb\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1237 (95.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e682 (94.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e555 (97.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e\u003cb\u003e0.030\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTBIL(\u0026gt;\u0026thinsp;28\u0026micro;mol/L)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e40 (3.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e20 (2.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e20 (3.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.556\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTBIL(\u0026micro;mol/L)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e13.3 (10.1, 17.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e13.1 (9.8, 17.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e13.4 (10.4, 17.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.228\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eALT(\u0026gt;\u0026thinsp;40U/L)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e565 (43.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e310 (43.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e255 (44.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.588\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eALT (U/L)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e37 (26, 57)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e36(25, 56)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e37 (27, 57)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.157\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAST(\u0026gt;\u0026thinsp;40U/L)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e639 (49.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e321 (44.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e318 (55.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAST (U/L)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e40 (30, 59)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e38 (28, 55)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e44 (32, 65)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eALB(\u0026lt;\u0026thinsp;40g/L)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e404 (31.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e217 (30.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e187 (32.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.337\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eALB (g/L)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e42.2 (39.3, 44.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e42.3 (39.4, 44.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e42.0 (39.0, 44.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.307\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eGLU(\u0026gt;\u0026thinsp;6.1mmol/L)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e208 (16.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e123 (17.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e85 (14.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.327\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePLT(\u0026gt;\u0026thinsp;100*10^9/L)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e240 (18.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e135 (18.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e105 (18.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.935\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePLT (10^9/L)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e154 (111, 204)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e147 (108, 201)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e163 (114, 206)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e\u003cb\u003e0.010\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNeutrophil (10^9/L)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e3.39 (2.66, 4.38)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e3.37 (2.59, 4.32)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e3.43 (2.70, 4.40)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.140\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eLymphocyte (10^9/L)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.44 (1.14, 1.80)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1.45 (1.15, 1.83)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e1.44 (1.12, 1.77)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.083\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCrea (\u0026micro;mol/L)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e72.1 (64.0, 83.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e72.1 (64.0, 83.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e72.6 (64.0, 82.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.868\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNLR*\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e646 (50.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e353 (49.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e293 (51.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.433\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePLR*\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e646 (50.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e324 (44.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e322 (56.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eLiver cirrhosis\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e545 (42.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e295 (40.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e250 (43.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.327\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTumor size(cm)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e7.5 (6.0, 10.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e7.0 (6.0, 9.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e8.0 (6.5, 10.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCapsular invasion\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e740 (57.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e378 (52.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e362 (63.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePoorly differentiated Tumor\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e524 (40.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e262 (36.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e262 (45.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e\u003cb\u003e0.001\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMVI\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e498 (38.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0 (0.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e498 (87.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSatellite lesion\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e146 (11.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0 (0.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e146 (25.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAFP(\u0026gt;\u0026thinsp;400ng/mL)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e519 (40.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e247 (34.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e272 (47.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePostoperative adjuvant TACE\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e353(27.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e137(19)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e216(31.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"5\"\u003eTBIL: total bilirubin, ALT: alanine aminotransferase, AST: aspartate aminotransferase, GLU: blood glucose level, ALB: albumin, PLT: platelet, PLR: platelet-to-lymphocyte ratio, NLR: neutrophil-to-lymphocyte ratio, MVI: microvascular invasion, AFP: alpha-fetoprotein\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd colspan=\"5\"\u003e* graded by median value\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003c/div\u003e\n\u003ch3\u003eThe mVI/S burden re-stratified SLHCC\u003c/h3\u003e\n\u003cp\u003eSurvival analysis demonstrated that the 1, 3, 5, 10-year of RFS were 70.5%, 50.8%, 38.6% and 20.1%, respectively, for SLHCC patients, and the 1, 3, 5, 10-year of OS were 88.2%, 67.7%, 56% and 39.4%, respectively, respectively, for SLHCC patients (\u003cb\u003eFigure S2\u003c/b\u003e). In subgroup analysis, the 1, 3, 5, 10-year of RFS were 79.3%, 60.1%, 46.2% and 24.6%, respectively for non-aggressive SLHCC patients, and 59.4%, 39.1%, 28.7% and 13.8%, respectively, for aggressive SLHCC patients (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001, Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e1\u003c/span\u003ea). The 1, 3, 5, 10-year of OS were 92.0%, 76.1%, 65.4% and 51.7%, respectively, for non-aggressive SLHCC patients, and 83.5%, 57.1%, 44.9% and 21.2%, respectively, for aggressive SLHCC patients (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001, Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e1\u003c/span\u003eb). Non-aggressive SLHCC patients had significant better prognosis than that of aggressive SLHCC patients.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cdiv id=\"Sec11\" class=\"Section2\"\u003e\u003ch2\u003eThe role of postoperative adjuvant TACE in SLHCC\u003c/h2\u003e\u003cp\u003e216 (31.8%) patients received postoperative adjuvant TACE in aggressive group, while in non-aggressive group, 137 (19%) patients received postoperative adjuvant TACE. Survival analysis demonstrated that the 1, 3, 5, 10-year of RFS were 78.5%, 57.7%, 43.8% and 20.5%, respectively for SLHCC patients with postoperative adjuvant TACE, and 67.5%, 48.2%, 36.7% and 20.1%, respectively, for SLHCC patients without postoperative adjuvant TACE (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001, \u003cb\u003eFigure S3\u003c/b\u003e). The 1, 3, 5, 10-year of OS were 93.8%, 69.6%, 56.8% and 36.9%, respectively for SLHCC patients with postoperative adjuvant TACE, and 86.1%, 67%, 55.6% and 39.9%, respectively, for SLHCC patients without postoperative adjuvant TACE (p\u0026thinsp;=\u0026thinsp;0.72, \u003cb\u003eFigure S3\u003c/b\u003e).\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eAmong patients with non-aggressive SLHCC, the 1, 3, 5, 10-year of RFS were 93.4%, 75%, 56.8% and 25.3%, respectively for patients with postoperative adjuvant TACE, and 76%, 56.6%,43.7% and 24.8%, respectively, for patients without postoperative adjuvant TACE (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.043, Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e2\u003c/span\u003ea). After adjusting tumor size, tumor differentiation, capsular invasion, AFP, HBsAg, HBeAg, liver cirrhosis, elevated ALT and elevated AST, this difference in term of RFS was consistent in the IPTW analyses (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.018, Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e2\u003c/span\u003ec). The 1, 3, 5, 10-year of OS were 98.5%, 81.7%, 64.9% and 50.9%, respectively, for patients with postoperative adjuvant TACE, and 90.4%, 74.7%,64.3% and 51.8%, respectively, for patients without postoperative adjuvant TACE (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.52, Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e2\u003c/span\u003eb). The IPTW analyses confirmed the results (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.249, Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e2\u003c/span\u003ed).\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eAmong patients with aggressive SLHCC subgroup, the 1, 3, 5, 10-year of RFS were 69%, 46.7%, 35.6% and 18.1%, respectively for patients with postoperative adjuvant TACE, and 53.5%, 34.4%, 24.5% and 11.4%, respectively, for patients without postoperative adjuvant TACE (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001, Fig.\u0026nbsp;\u003cspan refid=\"Fig6\" class=\"InternalRef\"\u003e3\u003c/span\u003ea). The 1, 3, 5, 10-year of OS were 90.7%,61.9%, 52.4% and 25.5%, respectively, for patients with postoperative adjuvant TACE, and 79.1%, 54.2%,40.9% and 19.2%, respectively, for patients without postoperative adjuvant TACE (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.033, Fig.\u0026nbsp;\u003cspan refid=\"Fig6\" class=\"InternalRef\"\u003e3\u003c/span\u003eb). After adjusting tumor size, tumor differentiation, capsular invasion, AFP, HBsAg, HBeAg, liver cirrhosis, elevated ALT and elevated AST, this difference in term of RFS and OS were consistent in the IPTW analyses (RFS: \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001, Fig.\u0026nbsp;\u003cspan refid=\"Fig6\" class=\"InternalRef\"\u003e3\u003c/span\u003ec; OS: \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.029, Fig.\u0026nbsp;\u003cspan refid=\"Fig6\" class=\"InternalRef\"\u003e3\u003c/span\u003ed).\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec12\" class=\"Section2\"\u003e\u003ch2\u003ePrognostic factors for SLHCC patients\u003c/h2\u003e\u003cp\u003eAs shown in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e. Multivariate analyses revealed that the following factors were associated with RFS: tumor size (HR:1.07), capsular invasion (HR:1.20), mIV/S (HR:1.53), HBsAg (HR:1.32), HBeAg (HR:1.31), postoperative adjuvant TACE (HR:0.73), liver cirrhosis (HR:1.20), tumor differentiation (HR:1.31) and elevated AST (HR:1.26). Similarly, multivariate analysis identified that tumor size (HR:1.07), capsular invasion (HR:1.49), mIV/S (HR:1.79), HBeAg (HR:1.30), AFP above 400ng/mL (HR:1.19), liver cirrhosis (HR:1.33), elevated ALT (HR:1.22) were predictors of OS (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). Subgroup analysis using Cox multivariate regression revealed that postoperative adjuvant TACE was associated with RFS (HR: 0.74,95%CI:0.58\u0026ndash;0.93, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.011), but not OS (HR:0.91 95%CI:0.68\u0026ndash;1.22, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.523) in non-aggressive SLHCC, and was associated with RFS (HR:0.68,95%CI:0.53\u0026ndash;0.87, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001) and OS (HR:0.72 95%CI:0.57\u0026ndash;0.91, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.007) in aggressive SLHCC (\u003cb\u003eTable S1 and Table S2\u003c/b\u003e).\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003ePredictive factors for recurrence free survival after hepatectomy\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"7\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colspan=\"3\" nameend=\"c4\" namest=\"c2\"\u003e\u003cp\u003eUnivariate analysis\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colspan=\"3\" nameend=\"c7\" namest=\"c5\"\u003e\u003cp\u003eMultivariate analysis\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eVariable\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eHR\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e95%CI\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003ep value\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eHR\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e95%CI\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003ep value\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAge (\u0026gt;\u0026thinsp;60 y)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.69\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.60\u0026ndash;0.81\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.87\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.75\u0026ndash;1.04\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.116\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eGender (male vs female)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.11\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.91\u0026ndash;1.36\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.299\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHBsAg\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.66\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1.38-2.00\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e1.32\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e1.06\u0026ndash;1.64\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e\u003cb\u003e0.012\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHBeAg\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.65\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1.39\u0026ndash;1.96\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e1.31\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e1.09\u0026ndash;1.57\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e\u003cb\u003e0.003\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHBcAb\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.45\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1.00-2.09\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.052\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.92\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.61\u0026ndash;1.38\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.68\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTBIL(\u0026gt;\u0026thinsp;28\u0026micro;mol/L)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.03\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.69\u0026ndash;1.54\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.868\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eALT(\u0026gt;\u0026thinsp;40U/L)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.28\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1.12\u0026ndash;1.47\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e1.05\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.89\u0026ndash;1.24\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.56\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAST(\u0026gt;\u0026thinsp;40U/L)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.57\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1.37\u0026ndash;1.80\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e1.26\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e1.06\u0026ndash;1.51\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e\u003cb\u003e0.01\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eALB(\u0026lt;\u0026thinsp;40g/L)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.07\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.92\u0026ndash;1.24\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.391\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eGLU(\u0026gt;\u0026thinsp;6.1mmol/L)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.86\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.70\u0026ndash;1.04\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.117\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNLR\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.06\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.92\u0026ndash;1.22\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.398\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePLR\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.10\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.96\u0026ndash;1.26\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.186\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAFP(\u0026gt;\u0026thinsp;400ng/mL)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.32\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1.15\u0026ndash;1.51\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e1.11\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.96\u0026ndash;1.29\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.147\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eLiver cirrhosis\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.29\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1.12\u0026ndash;1.48\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e1.20\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e1.04\u0026ndash;1.51\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e\u003cb\u003e0.013\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTumor size\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.07\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1.05\u0026ndash;1.10\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e1.04\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e1.02\u0026ndash;1.07\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e\u003cb\u003e0.002\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003emIV/S\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.74\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1.51\u0026ndash;1.99\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e1.53\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e1.32\u0026ndash;1.76\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCapsular invasion\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.35\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1.17\u0026ndash;1.56\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e1.20\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e1.03\u0026ndash;1.38\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e\u003cb\u003e0.016\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePoorly differentiated tumor\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.26\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1.10\u0026ndash;1.45\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e0.001\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e1.31\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e1.09\u0026ndash;1.57\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e\u003cb\u003e0.004\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePostoperative adjuvant TACE\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.84\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.73\u0026ndash;0.98\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e0.023\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.73\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.63\u0026ndash;0.85\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"7\"\u003eHR:hazard ratio; TBIL: total bilirubin, ALT: alanine aminotransferase, AST: aspartate aminotransferase, GLU: blood glucose level, ALB: albumin, PLT: platelet, PLR: platelet-to-lymphocyte ratio, NLR: neutrophil-to-lymphocyte ratio, MVI: microvascular invasion, AFP: alpha-fetoprotein;TACE:transhepatic arterial chem otherapy and embolization.\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab5\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003ePredictive factors for overall survival after hepatectomy\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"7\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colspan=\"3\" nameend=\"c4\" namest=\"c2\"\u003e\u003cp\u003eUnivariate analysis\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colspan=\"3\" nameend=\"c7\" namest=\"c5\"\u003e\u003cp\u003eMultivariate analysis\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eHR\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e95%CI\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003ep value\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eHR\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e95%CI\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003ep value\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAge (\u0026gt;\u0026thinsp;60 y)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.85\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.72\u0026ndash;1.01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.065\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e1.08\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.89\u0026ndash;1.30\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.44\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eGender (male vs female)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.14\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.91\u0026ndash;1.43\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.266\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHBsAg\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.50\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1.22\u0026ndash;1.85\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e1.18\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.94\u0026ndash;1.48\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.15\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHBeAg\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.60\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1.31\u0026ndash;1.94\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e1.30\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e1.06\u0026ndash;1.60\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e\u003cb\u003e0.013\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHBcAb\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.39\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.91\u0026ndash;2.13\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.125\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTBIL(\u0026gt;\u0026thinsp;28\u0026micro;mol/L)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.96\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.60\u0026ndash;1.53\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.849\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eALT(\u0026gt;\u0026thinsp;40U/L)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.38\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1.18\u0026ndash;1.61\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e1.22\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e1.05\u0026ndash;1.47\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e\u003cb\u003e0.044\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAST(\u0026gt;\u0026thinsp;40U/L)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.61\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1.37\u0026ndash;1.89\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e1.16\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.95\u0026ndash;1.42\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.146\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eALB((\u0026lt;\u0026thinsp;40g/L))\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.26\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1.07\u0026ndash;1.48\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e0.006\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e1.09\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.92\u0026ndash;1.30\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.303\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eGLU(\u0026gt;\u0026thinsp;6.1mmol/L)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.89\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.72\u0026ndash;1.11\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.318\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNLR\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.24\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1.06\u0026ndash;1.46\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e0.006\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e1.18\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.99\u0026ndash;1.40\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.06\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePLR\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.17\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1.00-1.37\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e0.054\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.93\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.78\u0026ndash;1.11\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.403\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAFP(\u0026gt;\u0026thinsp;400ng/mL)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.40\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1.20\u0026ndash;1.65\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e1.19\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e1.02\u0026ndash;1.41\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e\u003cb\u003e0.033\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eLiver cirrhosis\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.35\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1.15\u0026ndash;1.57\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e1.33\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e1.13\u0026ndash;1.56\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e\u003cb\u003e0.001\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTumor size\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.09\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1.07\u0026ndash;1.12\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e1.07\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e1.04\u0026ndash;1.09\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003emIV/S\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.90\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1.62\u0026ndash;2.23\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e1.79\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e1.52\u0026ndash;2.11\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCapsular invasion\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.64\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1.39\u0026ndash;1.94\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e1.49\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e1.26\u0026ndash;1.76\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePoorly differentiated tumor\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.43\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1.22\u0026ndash;1.67\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e1.16\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.99\u0026ndash;1.30\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.065\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePostoperative adjuvant TACE\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.98\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.83\u0026ndash;1.17\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.843\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"7\"\u003eHR:hazard ratio; TBIL: total bilirubin, ALT: alanine aminotransferase, AST: aspartate aminotransferase, GLU: blood glucose level, ALB: albumin, PLT: platelet, PLR: platelet-to-lymphocyte ratio, NLR: neutrophil-to-lymphocyte ratio, MVI: microvascular invasion, AFP: alpha-fetoprotein;TACE:transhepatic arterial chem otherapy and embolization.\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eSLHCC was a subgroup of solitary HCC. In current study, we included relatively large sample of SLHCC with long-term follow-up. The overall 5- and 10-year survival was 56% and 39.4%, which was significantly worse than that of patient with early-stage HCC\u003csup\u003e\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e\u003c/sup\u003e. Therefore, we contended that simply classifying SLHCC as early-stage HCC might be inappropriate. The presence of MVI in HCC was well-established predictor of tumor biology, which indicated a potential tumor disseminate and had negative impact on HCC prognosis after hepatectomy or liver transplantation\u003csup\u003e\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e\u003c/sup\u003e. Among 1292 SLHCC patients, the rate of MVI was 38.5%. Satellite lesion was significantly associated with poorly differentiated HCC, indicating potential tumor disseminate\u003csup\u003e\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e\u003c/sup\u003e. The rate of satellite lesion was 11.3% in SLHCC patients.73 SLHCC patients (5.6%) had both MVI and satellite lesion. Satellite lesions and MVI could significantly modify survival probabilities of HCC patients\u003csup\u003e\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u003c/sup\u003e. In current study, we further classified SLHCC into aggressive SLHCC and non-aggressive SLHCC based on the status of mVI/S burden. As result of our data analysis, patient with aggressive SLHCC had more unfavorable tumor characteristics, such as elevated AFP, capsular invasion and poorly differentiated HCC. Based on the survival analysis, patients with non-aggressive SLHCC had significantly better long-term survival than those with aggressive SLHCC, showing the 5 and 10-year survival rate of only 44.9% and 31.2%, respectively. The prognosis of non-aggressive SLHCC patients was comparable to that of patents within early-stage HCC\u003csup\u003e\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e\u003c/sup\u003e, while the prognosis of aggressive SLHCC patients was significantly inferior. Tumor biology was the fundamental factor that determined the prognosis of HCC patients\u003csup\u003e\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u003c/sup\u003e. How to select proper indicator for tumor biology was critical. Despite numerous gene signature was explored to reflect tumor aggressiveness, it was limited for its expensive and ineffective\u003csup\u003e\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e\u003c/sup\u003e. Tumor characteristics detected by microscope remained to be mainstay to designate tumor biology. In current study, we selected the status of mVI/S to determine the aggressivity of HCC. The presence of mVI/S was identified to be the only independent risk factor for aggressive recurrence and mortality in single HCC\u003csup\u003e\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u003c/sup\u003e. Unlike the growth of cholangiocarcinoma, HCC commonly enlarged with expansive growth. From the surgery standpoint, complete remove of tumor might be technically feasible. However, clinical implementation is often constrained by two key factors: (1) HCC commonly occurred with underlying liver fibrosis, and (2) patients with large HCC hardly achieved wide surgical margin, particularly when tumors are adjacent to critical vascular structures. The presence of mVI/S increased risk of recurrence. For those with non-aggressive SLHCC, surgical resection tended to achieve radical remove of tumor.\u003c/p\u003e\u003cp\u003eTumor size was hotly debated for its role in patient survival. Kokudo et al\u003csup\u003e20\u003c/sup\u003e identified that tumor size was not a prognostic factor. Solitary HCC\u0026thinsp;\u0026gt;\u0026thinsp;10cm would be a good candidate for hepatectomy as well as solitary HCC between 5 and 10cm\u003csup\u003e\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e\u003c/sup\u003e. Our study suggested that among patients with SLHCC, tumor size had negative effects on the prognosis in term of RFS and OS. This phenomenon might be attributable to the association between increasing tumor size and established adverse prognostic indicators, including vascular invasion status and histologic differentiation grade. Capsular invasion, AFP above 400ng/mL and poorly tumor differentiation was identified as risk factors for SLHCC patients. Among SLHCC patients, over 50% of patients had capsular invasion; and 40.2% had AFP\u0026thinsp;\u0026gt;\u0026thinsp;400ng/mL, and 40.6% had poorly tumor differentiation. Particularly, aggressive SLHCC had higher rate of these above-mentioned tumor characteristics. On the other hand, liver cirrhosis and status of HBV was significantly associated with prognosis of SLHCC patients. In China, the majority of HCC occurred in hepatitis B and liver cirrhosis. Despite surgery could completely remove the tumor, underlying liver disease and viral replication had been validated to contribute to tumor recurrence\u003csup\u003e\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e\u003c/sup\u003e. Active antiviral therapy aided to reduce the rate of tumor recurrence and prolong long-term survival\u003csup\u003e\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eAdjuvant TACE was expected to improve prognosis of HCC patients at high risk of recurrence. Zhou et al. \u003csup\u003e13\u003c/sup\u003e reported that adjuvant TACE improved outcomes in HBV-related HCC patients with intermediate or high recurrence risk post-hepatectomy, demonstrating a 12.9% increase in RFS and a 7.8% higher 3-year OS rate. Cheng et al suggested adjuvant TACE was associated with a lower risk of death among advanced HCC\u003csup\u003e\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u003c/sup\u003e. In our study, we found that adjuvant TACE improved prognosis of aggressive SLHCC, but not for non-aggressive SLHCC. Non-aggressive SLHCC patients seemed to gain less long-term survival benefits from adjuvant TACE. This might be due to relative benign tumor characteristics for non-aggressive SLHCC. Supporting our findings, adjuvant TACE rarely improve prognosis of American Joint Committee on Cancer TNM stage I or II HCC\u003csup\u003e\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e\u003c/sup\u003e. Patients with high risk of recurrence benefited from adjuvant TACE\u003csup\u003e\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u003c/sup\u003e. For aggressive SLHCC patients, they were at high risk of potential tumor dissemination. Adjuvant TACE could treat any pre-existing microscopic tumor foci or occult intrahepatic multifocality, improving the prognosis of HCC patients with highly aggressive tumors\u003csup\u003e\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e\u003c/sup\u003e. Our results also demonstrated effectiveness in the adjuvant setting for patients with aggressive SLHCC. Consistently, Cheng et al. demonstrating that adjuvant TACE was beneficial for be beneficial for HCC patients with MVI\u003csup\u003e\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eThere are some limitations in this study. First, this is a retrospective. We adopted multicenter data to overcome the section bias. Secondly, the majority of HCC patients in the current study had history of hepatitis B virus infection, which was different from the Western countries (predominantly hepatitis C virus infection). Thirdly, some date such as HBV-DNA was completely recorded, in current study, we did not include them to further analyze. However, all the antiviral regimen for HBV treatment was recommended based on guideline and patients received regular follow-up after surgery.\u003c/p\u003e\u003cp\u003eIn conclusion, our findings demonstrated that mVI/S status effectively stratified SLHCC into distinct prognostic subgroups: non-aggressive and aggressive variants. Notably, non-aggressive SLHCC patients exhibited favorable outcomes comparable to early-stage HCC. Adjuvant TACE significantly improved both RFS and OS in aggressive SLHCC, its prophylactic benefit appeared limited in non-aggressive cases, showing only marginal RFS improvement without significant OS advantage.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003ch2\u003eConflict of interest\u003c/h2\u003e\u003cp\u003eNone\u003c/p\u003e\u003c/p\u003e\u003cp\u003e\u003ch2\u003eEthic statement\u003c/h2\u003e\u003cp\u003e The protocol for this research project was approved by Ethics Committee of west China hospital, and written informed consent was obtained from all patients. This study conformed to the provisions of the Declaration of Helsinki.\u003c/p\u003e\u003c/p\u003e\u003ch2\u003eFunding\u003c/h2\u003e\u003cp\u003eThis study was supported by the Natural Science Foundation of Sichuan Province (No. 2025ZNSFSC1920), and the \"Qimingxing\" Research Fund for Young Talents of West China Hospital (No. HXQMX0062), and the West China Hospital Incubation Project (No. 22HXFH011).\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eChuwen Chen: Conceptualization, Data curation, Formal analysis, Investigation, Methodology, Writing original draft,Writing review \u0026amp; editing.Qing Tao: Investigation, Resources, Software, Validation, Visualization.Changli Lu: Data curation, Project administration, Supervision, Validation.Yu Zhang: Formal analysis, Methodology, Resources, Software.Shusheng Leng: Data curation, Supervision.Tianfu Wen: Conceptualization, Supervision, Writing \u0026ndash; review \u0026amp; editing.Junyi Shen: Methodology, Project administration, Supervision, Validation, Writing \u0026ndash; review \u0026amp; editing.\u003c/p\u003e\u003ch2\u003eAcknowledgement\u003c/h2\u003e\u003cp\u003eNO\u003c/p\u003e\u003ch2\u003eData Availability\u003c/h2\u003e\u003cp\u003eThe data that support the findings of this study are available from the corresponding author upon request.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eWang FS, Fan JG, Zhang Z, Gao B, Wang HY. 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J Surg Oncol. 2016;113(1):89\u0026ndash;93.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eFuster-Anglada C, Mauro E, Ferrer-F\u0026agrave;brega J, et al. Histological predictors of aggressive recurrence of hepatocellular carcinoma after liver resection. J Hepatol. 2024;81(6):995\u0026ndash;1004.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eBruix J, Takayama T, Mazzaferro V, et al. Adjuvant sorafenib for hepatocellular carcinoma after resection or ablation (STORM): a phase 3, randomised, double-blind, placebo-controlled trial. Lancet Oncol. 2015;16(13):1344\u0026ndash;54.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eQin S, Chen M, Cheng AL, et al. Atezolizumab plus bevacizumab versus active surveillance in patients with resected or ablated high-risk hepatocellular carcinoma (IMbrave050): a randomised, open-label, multicentre, phase 3 trial. Lancet (London England). 2023;402(10415):1835\u0026ndash;47.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eLi SH, Mei J, Cheng Y, et al. Postoperative Adjuvant Hepatic Arterial Infusion Chemotherapy With FOLFOX in Hepatocellular Carcinoma With Microvascular Invasion: A Multicenter, Phase III, Randomized Study. J Clin oncology: official J Am Soc Clin Oncol. 2023;41(10):1898\u0026ndash;908.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eWang Z, Ren Z, Chen Y, et al. Adjuvant Transarterial Chemoembolization for HBV-Related Hepatocellular Carcinoma After Resection: A Randomized Controlled Study. Clin cancer research: official J Am Association Cancer Res. 2018;24(9):2074\u0026ndash;81.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eLiu S, Guo L, Li H, et al. Postoperative Adjuvant Trans-Arterial Chemoembolization for Patients with Hepatocellular Carcinoma and Portal Vein Tumor Thrombus. Ann Surg Oncol. 2018;25(7):2098\u0026ndash;104.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eAn C, Kim DW, Park YN, Chung YE, Rhee H, Kim MJ. Single Hepatocellular Carcinoma: Preoperative MR Imaging to Predict Early Recurrence after Curative Resection. Radiology. 2015;276(2):433\u0026ndash;43.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eZeng JS, Zeng JX, Huang Y, Liu JF, Zeng JH. The effect of adjuvant transarterial chemoembolization for hepatocellular carcinoma after liver resection based on risk stratification. Hepatobiliary Pancreat Dis international: HBPD INT. 2023;22(5):482\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eMa T, Bai X, Zhang Q et al. Adjuvant transarterial chemoembolization for hepatocellular carcinoma following curative resection: A randomized, open-label, phase 3 trial. Hepatology (Baltimore MD). 2025.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eSu JY, Huang DJ, Liu SP et al. Adjuvant Transarterial Chemoembolization After Truly Curative Resection Does Not Improve Survival of Patients With Hepatocellular Carcinoma at High Risk of Recurrence: A Target Trial Emulation Study. Hepatol research: official J Japan Soc Hepatol. 2025.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eWang JH, Wang CC, Hung CH, Chen CL, Lu SN. Survival comparison between surgical resection and radiofrequency ablation for patients in BCLC very early/early stage hepatocellular carcinoma. J Hepatol. 2012;56(2):412\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eLim C, Mise Y, Sakamoto Y, et al. Above 5 cm, size does not matter anymore in patients with hepatocellular carcinoma. World J Surg. 2014;38(11):2910\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eLee S, Kang TW, Song KD, et al. Effect of Microvascular Invasion Risk on Early Recurrence of Hepatocellular Carcinoma After Surgery and Radiofrequency Ablation. Ann Surg. 2021;273(3):564\u0026ndash;71.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eShen J, Dai J, Zhang Y, et al. Baseline HBV-DNA load plus AST/ALT ratio predicts prognosis of HBV-related hepatocellular carcinoma after hepatectomy: A multicentre study. J Viral Hepatitis. 2021;28(11):1587\u0026ndash;96.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eShen J, Qi W, Dai J, et al. Tenofovir vs. entecavir on recurrence of hepatitis B virus-related hepatocellular carcinoma beyond Milan criteria after hepatectomy. Chin Med J. 2021;135(3):301\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003ePanettieri E, Campisi A, De Rose AM et al. Emerging Prognostic Markers in Patients Undergoing Liver Resection for Hepatocellular Carcinoma: A Narrative Review. Cancers 2024;16(12).\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eAufhauser DD Jr., Sadot E, Murken DR, et al. Incidence of Occult Intrahepatic Metastasis in Hepatocellular Carcinoma Treated With Transplantation Corresponds to Early Recurrence Rates After Partial Hepatectomy. Ann Surg. 2018;267(5):922\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eSun JJ, Wang K, Zhang CZ, et al. Postoperative Adjuvant Transcatheter Arterial Chemoembolization After R0 Hepatectomy Improves Outcomes of Patients Who have Hepatocellular Carcinoma with Microvascular Invasion. Ann Surg Oncol. 2016;23(4):1344\u0026ndash;51.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-cancer","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bcan","sideBox":"Learn more about [BMC Cancer](http://bmccancer.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bcan/default.aspx","title":"BMC Cancer","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"microvascular invasion, satellite lesion, solitary, hepatocelluar carcinoma, hepatectomy, adjuvant therapy","lastPublishedDoi":"10.21203/rs.3.rs-7792877/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7792877/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground:\u003c/strong\u003e Adjuvant therapy for solitary large hepatocellular carcinoma (SLHCC) remained unclear.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods: \u003c/strong\u003e1292 SLHCC patients treated with hepatectomy between January 2010 and December 2020 were included in this retrospective cohort study investigating adjuvant transarterial chemoembolization (TACE), recurrence free survival (RFS) and overall survival (OS).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults:\u003c/strong\u003e Among the study cohort, 571 SLHCC patients (44.2%) with microvascular invasion and/or satellite lesion (mVI/S) burden were classified as aggressive SLHCC, while 721 patients without mVI/S were classified as non-aggressive SLHCC, showing significantly better 10-year OS rates (51.7% versus 21.2%, \u003cem\u003ep\u003c/em\u003e\u0026lt;0.001). Adjuvant TACE could significantly improve RFS in non-aggressive SLHCC patients, with 5- and 10-year RFS rates of 56.8% and 25.3% (vs. 43.7% and 24.8% in untreated patients, \u003cem\u003ep\u003c/em\u003e=0.043), a finding confirmed by inverse probability of treatment weighting (IPTW) analysis (\u003cem\u003ep\u003c/em\u003e=0.018). However, adjuvant TACE did not significantly impact OS in this group(\u003cem\u003ep\u003c/em\u003e=0.52; IPTW:\u003cem\u003ep\u003c/em\u003e=0.249). For aggressive SLHCC patients, adjuvant TACE showed benefits in both RFS (5-year: 35.6% vs 24.5%; 10-year: 18.1% vs 11.4%, \u003cem\u003ep\u003c/em\u003e\u0026lt;0.001; IPTW:\u003cem\u003ep\u003c/em\u003e\u0026lt;0.001)) and OS (5-year: 52.4% vs 40.9%; 10-year: 25.5% vs 19.2%, \u003cem\u003ep\u003c/em\u003e=0.033; IPTW:\u003cem\u003ep\u003c/em\u003e=0.029). The mVI/S burden was independent predictors of RFS (HR：1.53, 95%CI:1.32-1.76, \u003cem\u003ep\u003c/em\u003e\u0026lt;0.001) and OS (HR：1.79, 95%CI:1.52-2.11, \u003cem\u003ep\u003c/em\u003e\u0026lt;0.001) for SLHCC. Adjuvant TACE was associated with RFS (HR：0.74 95%CI:0.58-0.93, \u003cem\u003ep\u003c/em\u003e=0.011) but not OS (HR：0.91, 95%CI:0.68-1.22, \u003cem\u003ep\u003c/em\u003e=0.523) for non-aggressive SLHCC, while demonstrating significant benefit for RFS (HR：0.68, 95%CI:0.53-0.87, \u003cem\u003ep\u003c/em\u003e\u0026lt;0.001) and OS (HR：0.72, 95%CI:0.57-0.91, \u003cem\u003ep\u003c/em\u003e=0.007) for aggressive SLHCC.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusions:\u003c/strong\u003e The mVI/S burden identified aggressive SLHCC subtypes. Adjuvant TACE improved both RFS and OS in aggressive SLHCC, but only RFS (not OS) in non-aggressive cases.\u003c/p\u003e","manuscriptTitle":"Adjuvant transarterial chemoembolization for solitary large hepatocellular carcinoma by microvascular invasion and/or satellite lesion burden：A Multi-Center Retrospective Study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-11-11 16:30:57","doi":"10.21203/rs.3.rs-7792877/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"reviewersInvited","content":"","date":"2025-10-30T16:19:49+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2025-10-09T08:03:24+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-10-08T01:52:23+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-10-08T01:52:08+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Cancer","date":"2025-10-06T16:00:00+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-cancer","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bcan","sideBox":"Learn more about [BMC Cancer](http://bmccancer.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bcan/default.aspx","title":"BMC Cancer","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"f5e78cc7-b474-4c33-9399-adb7a78aa6ad","owner":[],"postedDate":"November 11th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2025-11-11T16:30:57+00:00","versionOfRecord":[],"versionCreatedAt":"2025-11-11 16:30:57","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7792877","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7792877","identity":"rs-7792877","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}