TACE Combined with PD-L1 Inhibitors Effectively Mitigates TACE Resistance in Advanced Hepatocellular Carcinoma: A Propensity Score-Matched Study

TACE Combined with PD-L1 Inhibitors Effectively Mitigates TACE Resistance in Advanced Hepatocellular Carcinoma: A Propensity Score-Matched 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 Article TACE Combined with PD-L1 Inhibitors Effectively Mitigates TACE Resistance in Advanced Hepatocellular Carcinoma: A Propensity Score-Matched Study Huyu Jiao, Xinmei Yan, Junxin Li, Zhengang Zhang This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6558171/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Transarterial chemoembolization (TACE) combined with PD-(L)1 inhibitors and molecular targeted therapies (MTT) has demonstrated significant improvements in progression-free survival (PFS), overall survival (OS).This retrospective study investigated TACE-PD-(L)1-MTT combination therapy's role in preventing TACE resistance in advanced HCC. Among 604 eligible patients (532 TACE alone vs. 72 combination) after propensity score matching, TACE resistance occurrence was evaluated post-3 treatment cycles. Combination therapy significantly reduced resistance incidence (9.7% vs. 38.8%, p < 0.001) and demonstrated superior efficacy in inhibiting tumor progression compared to TACE monotherapy. These findings support the preventive potential of triple combination therapy against TACE resistance while improving clinical outcomes in advanced HCC . Biological sciences/Cancer Health sciences/Medical research Health sciences/Oncology Figures Figure 1 Figure 2 Figure 3 Introduction Primary liver cancer, a frequently occurring malignancy, currently ranks sixth in global cancer incidence and third in cancer-related mortality 1 .Unfortunately, most patients are diagnosed at advanced stages, missing the optimal window for surgical intervention, leading to poor prognosis 2 .For advanced HCC, transarterial chemoembolization (TACE) remains the primary treatment modality 3 . However, a significant proportion of undifferentiated HCC (uHCC) patients experience disease progression within one year of TACE treatment. This progression is associated with enhanced interactions within the tumor microenvironment post-TACE, potentially contributing to post-treatment deterioration 4 . Clinical studies have shown that immunotherapies, including PD-1 and PD-L1 inhibitors, exhibit promising efficacy and safety profiles in phase I and II trials for advanced HCC 5 , 6 .Consequently, combining TACE with immunotherapy may achieve synergistic effects, potentially enhancing therapeutic outcomes. The primary mechanism underlying this combination involves TACE-induced antigen release and upregulation of PD-L1 expression, fostering an immunosuppressive microenvironment that augments responsiveness to PD-L1 inhibitors 7 . Numerous studies have confirmed that TACE combined with PD-(L)1 blockade and MTT significantly improves PFS, OS, and ORR in Chinese patients with advanced HCC, with acceptable safety profiles 8 .This study further substantiates the beneficial role of TACE combined with PD-(L)1 inhibitors and MTT in mitigating TACE resistance in advanced HCC. Methods This study strictly adhered to the guidelines outlined in the Declaration of Helsinki and received formal approval from the Ethics Committee of Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology (Ethics Approval Number: TJ-IRB202412142). Given the retrospective nature of the study, written informed consent was waived. The study design was based on the "Chinese Guidelines for the Diagnosis and Treatment of Primary Liver Cancer" and targeted patients clinically or pathologically diagnosed with HCC 9 .Patient data were collected between January 2020 and December 2024, including those who underwent TACE or TACE combined with PD-(L)1 inhibitors and MTT at our institution. Inclusion criteria were as follows: (1) Aged ≥ 18 years; (2) Barcelona Clinic Liver Cancer (BCLC) stage B or C HCC; (3) Received at least three cycles of TACE alone or TACE combined with PD-(L)1 inhibitors and MTT (defined as concurrent or sequential TACE and PD-(L)1 inhibitor administration within 60 days, combined with MTT); (4) Child-Pugh class A or B liver function; (5) Eastern Cooperative Oncology Group (ECOG) performance status score of 0–1; (6) Presence of at least one measurable target lesion assessable by Response Evaluation Criteria in Solid Tumors (RECIST). Exclusion criteria included: (1) Patients with other primary malignancies; (2) Patients receiving treatment regimens outside the study protocols; (3) Patients lost to follow-up or with incomplete medical records. Treatment Protocols TACE Treatment TACE was typically administered prior to the initiation of PD-L1 inhibitor therapy. During the procedure, patients received local anesthesia, followed by catheterization of the celiac trunk or superior mesenteric artery via a 5-French catheter, and subsequent angiography. A 2.7 French microcatheter was then navigated into the specific artery supplying the tumor. A mixture of 20 mg pirarubicin and 10 mL lipiodol was injected for embolization, followed by additional embolization using gelatin sponge particles until complete cessation of blood flow in the tumor-feeding artery was achieved. Anti-PD-(L)1 Drugs For patients receiving TACE combined with PD-(L)1 inhibitors and MTT, various PD-(L)1 inhibitors were selected based on treatment guidelines and drug availability in the Chinese market, including sintilimab, tislelizumab, and pembrolizumab. All selected PD-(L)1 inhibitors were administered according to their standard dosages and frequencies. Molecular Targeted Therapy For patients receiving TACE combined with PD-(L)1 inhibitors and MTT, various molecular targeted drugs were employed, including sorafenib, lenvatinib, apatinib, and bevacizumab (an anti-VEGF agent). All medications were initiated within two weeks post-TACE. Follow-Up and Assessment All patients underwent computed tomography (CT) and/or magnetic resonance imaging (MRI), liver function tests, complete blood counts, and tumor marker assessments within 1–3 months following each TACE session. TACE efficacy was evaluated using dynamic CT/MRI, and patients were categorized as having complete response (CR), partial response (PR), stable disease (SD), or progressive disease (PD) according to modified RECIST (mRECIST) criteria. Patients with PR, SD, or PD underwent subsequent TACE or TACE combined with PD-(L)1 inhibitors and MTT. The occurrence of TACE resistance was determined 1–3 months after three consecutive standardized and refined TACE sessions, based on enhanced CT/MRI findings indicating persistent disease progression (PD) of intrahepatic target lesions compared to baseline assessments, as per the Chinese definition of TACE resistance 10 . Statistical Analysis To control for confounding factors, 1:1 nearest-neighbor propensity score matching (PSM) was employed with a caliper width of 0.02 to ensure matching quality. Covariate balance was assessed using standardized mean differences (SMD), with a threshold of < 0.1 indicating adequate balance. Continuous variables were compared using independent samples t-tests (for normally distributed data, reported as mean ± standard deviation) or Mann-Whitney U tests (for non-normally distributed data, reported as median ± interquartile range). Categorical variables were analyzed using chi-square tests or Fisher's exact tests. Cox proportional hazards models were used to identify risk factors associated with TACE resistance (variables with p < 0.05 in univariate analysis were entered into multivariate analysis). Kaplan-Meier methods were used to plot OS and PFS curves. All analyses were performed using R (version 4.2.2) and SPSS (version 27.0). Two-tailed p-values < 0.05 were considered statistically significant. The proportional hazards assumption for the Cox model and the statistical power of the matched sample size were verified. Results Patient Baseline Characteristics We systematically reviewed clinical data of HCC patients treated at our institution between January 2020 and December 2024. Patients who underwent at least three consecutive TACE sessions, either alone or in combination with PD-(L)1 inhibitors and MTT, were included. After rigorous screening, 604 eligible patients were identified, comprising 532 who received TACE alone and 72 who received combination therapy(Fig. 1 ). Baseline characteristic analysis revealed that the combination therapy group exhibited greater tumor burden (mean maximum tumor diameter: 9.15 cm vs. 6.60 cm, p = 0.001) and a higher incidence of portal vein tumor thrombus (41.7% vs. 23.3%, p = 0.001). To minimize confounding, 1:1 PSM was performed, resulting in a balanced cohort of 144 patients (72 pairs). Post-matching, both groups were comparable in terms of male predominance, viral hepatitis history, and mean maximum tumor diameter (8.0 cm). No statistically significant differences were observed in any clinicopathological parameters between the groups (p > 0.05) (Table 1 ). Table 1 Baseline characteristics of patients in combination therapy group and monotherapy group before and after PSM. 0 N = 532 1 N = 72 p.overall 0 N = 72 1 N = 72 p.overall Gender: 0.882 0.325 wemen 59 (11.1%) 7 (9.72%) 12 (16.7%) 7 (9.72%) man 473 (88.9%) 65 (90.3%) 60 (83.3%) 65 (90.3%) Age 54.9 (10.6) 56.2 (10.5) 0.330 58.3 (11.0) 56.2 (10.5) 0.250 Comorbid Hepatitis B 0.184 0.669 No 75 (14.1%) 15 (20.8%) 12 (16.7%) 15 (20.8%) Yes 457 (85.9%) 57 (79.2%) 60 (83.3%) 57 (79.2%) White Blood Cells 5.23 [3.79;6.51] 5.67 [4.38;6.77] 0.094 5.88 [4.11;7.71] 5.67 [4.38;6.77] 0.453 Lymphocytes 1.19 [0.87;1.59] 1.31 [1.07;1.68] 0.031 1.23 [0.89;1.56] 1.31 [1.07;1.68] 0.128 Hemoglobin 133 [120;147] 138 [124;148] 0.304 132 [119;142] 138 [124;148] 0.169 Platelets 128 [80.2;190] 180 [130;226] < 0.001 154 [102;222] 180 [130;226] 0.110 Albumin 38.6 [34.9;42.2] 38.7 [36.3;41.7] 0.583 38.0 [35.5;42.0] 38.7 [36.3;41.7] 0.460 ALT 33.0 [23.0;52.0] 36.5 [22.0;54.2] 0.980 33.0 [20.8;48.0] 36.5 [22.0;54.2] 0.616 AST 44.0 [31.0;69.0] 53.5 [32.8;92.8] 0.046 47.0 [30.8;79.2] 53.5 [32.8;92.8] 0.306 Total_Bilirubin 14.9 [9.88;22.1] 15.3 [11.5;21.1] 0.475 14.4 [10.0;20.3] 15.3 [11.5;21.1] 0.361 AFP 0.826 0.170 <400 307 (57.7%) 40 (55.6%) 49 (68.1%) 40 (55.6%) ≥ 400 225 (42.3%) 32 (44.4%) 23 (31.9%) 32 (44.4%) APTT 38.5 [35.8;41.4] 36.0 [34.6;38.8] < 0.001 38.1 [33.8;39.5] 36.0 [34.6;38.8] 0.230 PT 14.1 [13.5;15.2] 13.3 [12.7;13.9] < 0.001 13.4 [12.8;14.3] 13.3 [12.7;13.9] 0.160 Fibrinogen 3.04 [2.45;3.95] 3.61 [2.91;4.54] 0.001 3.43 [2.74;4.33] 3.61 [2.91;4.54] 0.501 Primary Tumor Size 66.0 [37.8;100] 91.5 [57.5;122] < 0.001 85.0 [42.5;120] 91.5 [57.5;122] 0.370 Number of Tumors 0.192 0.577 No 178 (33.5%) 18 (25.0%) 22 (30.6%) 18 (25.0%) Yes 354 (66.5%) 54 (75.0%) 50 (69.4%) 54 (75.0%) Tumor Capsule: 0.130 0.489 No 163 (30.6%) 29 (40.3%) 24 (33.3%) 29 (40.3%) Yes 369 (69.4%) 43 (59.7%) 48 (66.7%) 43 (59.7%) Tumor Thrombus: 0.001 0.225 No 408 (76.7%) 42 (58.3%) 50 (69.4%) 42 (58.3%) Yes 124 (23.3%) 30 (41.7%) 22 (30.6%) 30 (41.7%) Bilobar Distribution of Tumor 0.446 0.867 No 320 (60.2%) 39 (54.2%) 37 (51.4%) 39 (54.2%) Yes 212 (39.8%) 33 (45.8%) 35 (48.6%) 33 (45.8%) Child Pugh Classification 0.366 A 488 (91.7%) 71 (98.6%) 0.098 69 (95.8%) 71 (98.6%) B 44 (8.3%) 1 (1.4%) 3 (4.2%) 1 (1.4%) Performance Status Score 1.000 0 456 (85.7%) 60 (83.3%) 0.719 61 (84.7%) 60 (83.3%) 1 76 (14.3%) 12 (16.7%) 11 (15.3%) 12 (16.7%) BCLC: 0.580 B 304 (57.2%) 32 (44.4%) 0.042 34 (47.2%) 32 (44.4%) C 228 (42.8%) 40 (53.6%) 38 (52.8%) 40 (53.6%) Clinical Outcomes All patients received three consecutive refined treatment cycles. Tumor progression was compared between the TACE-PD-(L)1-MTT combination group and the TACE monotherapy group. TACE resistance occurred in only 7 patients (9.7%) in the combination group, compared to 28 patients (38.8%) in the monotherapy group (Fig. 2 ). This difference was statistically significant (p < 0.001), indicating superior tumor progression control with combination therapy. Furthermore, the median follow-up durations were comparable between the combination and monotherapy groups (14.8 months [IQR 10.4–20.6] vs. 15.3 months [IQR 9.2–21.9], p = 0.23). Survival analysis demonstrated significant benefits with combination therapy: median PFS (mPFS) was 17.5 months (95% CI 15.7–19.3) in the combination group, an 8.4-month improvement over the monotherapy group's mPFS of 9.1 months (95% CI 6.2–12.2, p = 0.004) (Fig. 3 ). Median OS (mOS) reached 20.8 months in the combination group compared to 16.4 months (95% CI 11.3–21.5) in the monotherapy group, with a statistically significant difference (p = 0.0084). These data underscore the substantial advantages of combination therapy in prolonging PFS and OS. Finally, we analyzed risk factors for TACE resistance in 532 patients who developed resistance after TACE monotherapy. Univariate and multivariate logistic regression identified bilobar tumor distribution, maximum tumor diameter, and tumor capsule absence as independent risk factors for TACE resistance (Table 2 ). Table 2 Univariate and Multivariate Analysis of TACE Resistance Univariate logistic regression analysis Multivariate logistic regression analysis characteristics OR CI P OR CI P Age 0.98 0.97-1 0.128 Female 1.15 0.59–2.24 0.687 Comorbid Hepatitis B 1.06 0.56–2.01 0.858 White Blood Cells 1.13 1.04–1.24 0.005 1.09 0.95–1.22 0.09 Lymphocytes 1.03 0.95–1.12 0.445 Hemoglobin 1.12 0.99–1.21 0.96 Platelets 1.23 1-1.41 0.53 Albumin 1.02 0.98–1.06 0.361 ALT 1.43 1.21–1.65 0.67 AST 1.55 1.32–1.75 0.819 AFP ≥ 400 2.07 1.34–3.19 0.001 1.92 1.42–2.95 0.06 APTT 1.03 0.96–1.07 0.94 PT 0.91 0.79–1.04 0.177 Fibrinogen 1.36 1.15–1.61 0.23 Primary Tumor size 1.01 1.01–1.02 <0.001 1.01 1-1.02 0.001 Number of multiple tumors 1.96 1.21–3.18 0.006 Tumor Capsule 0.18 0.11–0.29 <0.001 0.29 0.17–0.48 0.002 Tumor Thrombus 4.52 2.74–7.47 0.03 Bilobar Distribution of Tumor 2.46 1.59–3.8 <0.001 2.13 1.3–3.48 0.003 Child Pugh Classification B 2.25 1.1–4.62 0.027 2.14 1.23–4.21 0.07 BCLC-B 2.56 0.92–7.14 0.073 BCLC-C 6.9 2.39–19.92 0.052 Safety Analysis After PSM, 48 of 72 patients (66.6%) in the combination group reported adverse events (AEs), compared to 35 of 72 patients (48.6%) in the monotherapy group (Table 3 ). Grade 3 or higher severe AEs (SAEs) occurred in 19.4% (combination group, 14 cases) and 9.7% (monotherapy group, 7 cases) of patients. No grade 5 life-threatening or fatal AEs were observed in either group. In the combination group, 5 patients (6.9%) required temporary discontinuation of lenvatinib due to treatment-related AEs, and 12 patients (16.6%) needed dose adjustments for PD-(L)1 immune checkpoint inhibitors and molecular targeted drugs. However, no patients discontinued treatment. All AEs were effectively managed through clinical interventions, and no treatment discontinuations or deaths occurred due to AEs. Table 3 Any-Cause Adverse Events in Combination Group vs. Monotherapy Group After PSM Variable Combination group ( n = 72) Monotherapy group ( n = 72) Patients with an adverse event from any cause 48 (66.6) 35 (48.6) Grade 1 or 2 event 34 (47.2) 28 (38.9) Grade 3 event 12 (16.7) 7 (9.7) Grade 4 event 2 (2.7) 0 Grade 5 event 0 0 Dose interruption of anti-PD-(L)1 therapies 5 (6.9) N/A Dose reduction or interruption of molecular targeted therapies 12 (16.6) N/A Discussion This study innovatively demonstrates that the combination of TACE with PD-(L)1 immune checkpoint inhibitors and MTT significantly reverses treatment resistance observed after three TACE cycles. In the core efficacy comparison, only 7 patients (9.7%) in the combination group exhibited target lesion progression, compared to 28 patients (38.8%) in the TACE monotherapy group, with a statistically significant difference (p < 0.01). Survival analysis further revealed a more favorable disease control trend with combination therapy, as evidenced by significantly superior PFS and OS compared to monotherapy. These findings strongly align with the recently published CHANCE001 multicenter retrospective study. This national cohort study (n = 867) demonstrated that TACE combined with PD-(L)1 inhibitors and MTT provides triple clinical benefits for advanced HCC patients: a 1.5-month prolongation of median PFS (HR = 0.76, p = 0.015), a 3.5-month prolongation of median OS (HR = 0.76, p = 0.001), and an increased ORR of 28.1% 8 .Notably, this study transcends traditional PFS definitions by innovatively focusing on intrahepatic target lesion progression as the primary endpoint, while considering new lesions, portal vein invasion, and extrahepatic metastases as secondary indicators. This evaluation framework more precisely reflects the biological characteristics of TACE resistance and offers clinically relevant insights for therapeutic assessment. Furthermore, this study identifies three core biological drivers of TACE resistance in advanced HCC: maximum tumor diameter, absence of tumor capsule integrity, and bilobar infiltrative growth. These indicators not only serve as independent prognostic markers but also represent critical targets for personalized treatment strategies. From a tumor biological perspective, the absence of tumor capsule integrity constitutes a significant warning signal. The pathological mechanism involves the tumor capsule acting as a natural barrier; its disruption enables tumor cells to breach fibrous matrix constraints and infiltrate along portal vein branches. This infiltrative growth pattern simultaneously compromises the integrity of tumor vascular architecture, promoting the formation of abnormal vascular networks between intra- and extra-tumoral vessels 11 .Clinical research confirms that such vascular remodeling significantly increases the risk of portal vein tumor thrombus formation, which represents an important anatomical basis for TACE treatment failure 12 . The prognostic value of bilobar infiltrative growth is validated in this study, aligning with Chen et al.'s meta-analysis of 1,238 patients 13 .The mechanism may involve enhanced intrahepatic metastatic potential of tumor cells, leading to multicentric lesion formation and significantly increasing treatment coverage challenges 14 . Maximum tumor diameter, established as an independent predictor of early TACE refractoriness, receives robust support in this study. Multiple investigations indicate that tumor size represents a critical prognostic factor in HCC patients 15 – 17 . Larger tumor diameters (≥ 5 cm) correlate with higher tumor burdens, rendering complete TACE coverage technically challenging 14 . Studies demonstrate that TACE-treated target lesions frequently develop compensatory blood supply through hepatofugal collateral arteries (e.g., inferior phrenic arteries, intercostal arteries) 18 . When the tumor diameter exceeds 5 cm, the incidence of extrahepatic collateral arterial supply increases significantly, which directly compromises therapeutic efficacy and is closely associated with treatment failure and poor prognosis 19 , 20 .These findings carry important clinical implications: for advanced HCC patients exhibiting these high-risk biological characteristics, early combination with systemic therapies (e.g., immuno-oncology combinations) or localized treatment escalation (e.g., embolic agents) should be considered 21 .This precision medicine approach, guided by tumor biological features, has the potential to overcome traditional TACE limitations and substantially improve patient outcomes. The remarkable efficacy observed in the combination therapy group can be attributed to multi-mechanistic synergies. TACE induces ischemic necrosis by embolizing tumor-feeding arteries while locally releasing chemotherapeutic agents to enhance cytotoxic effects. However, the hypoxic microenvironment in residual tumor cells post-TACE triggers VEGF upregulation, stimulating tumor angiogenesis and serving as a pathophysiological basis for disease progression 22 .Molecular targeted agents (e.g., lenvatinib, sorafenib) effectively block TACE-induced tumor vascular regeneration by inhibiting VEGF receptor signaling pathways, thereby delaying recurrence 23 , 24 .Concurrently, these agents normalize tumor vasculature, significantly optimizing the immune cell infiltration microenvironment and creating favorable conditions for immune checkpoint inhibitor efficacy 7 , 25 .The PD-1/PD-L1 axis plays a pivotal role in tumor immune evasion. Activation of this pathway suppresses T-cell activity, enabling tumor cells to evade immune surveillance 26 . PD-(L)1 inhibitors restore T-cell cytotoxic function by blocking inhibitory signals, thereby eliciting anti-tumor immune responses 27 .The triple combination forms a therapeutic loop encompassing "vascular occlusion, immune activation, and immune enhancement," exerting synergistic anti-tumor effects through three dimensions: tumor angiogenesis inhibition, immune microenvironment remodeling, and T-cell functional restoration. This synergy significantly elevates disease control rates 8 , 28 .Our study demonstrates that this triple combination substantially reduces target lesion progression post-TACE. For patients experiencing TACE resistance, treatment strategies require dynamic adjustment. Emerging research suggests targeting the hypoxic microenvironment with hypoxia-activated prodrugs (e.g., APX005M) or HIF-1α inhibitors may partially reverse TACE resistance 29 , 30 .However, standardized post-TACE resistance treatment protocols remain undefined, necessitating prospective studies to explore personalized therapeutic regimens. This study has several limitations. The retrospective design carries inherent risks of selection bias, as evidenced by baseline characteristic differences. To mitigate this, we employed PSM and conducted sensitivity analyses commonly used in real-world research. Additionally, the relatively small sample size necessitates larger cohort studies for more in-depth investigations. Conclusion Our study demonstrates the beneficial role of TACE combined with PD-(L)1 immune checkpoint inhibitors and MTT in mitigating TACE resistance in advanced HCC. Furthermore, it identifies maximum tumor diameter, bilobar infiltrative growth, and multiple tumor lesions as independent risk factors. These findings provide novel theoretical frameworks and practical directions for optimizing treatment strategies in patients with TACE resistance. Abbreviations TACE Transarterial Chemoembolization PD-(L)1 Programmed Death-Ligand 1 MTT Molecular Targeted Therapies HCC Hepatocellular Carcinoma PFS Progression-Free Survival OS Overall Survival ORR Objective Response Rate PSM Propensity Score Matching RECIST Response Evaluation Criteria in Solid Tumors mRECIST Modified RECIST CT Computed Tomography MRI Magnetic Resonance Imaging AFP Alpha-Fetoprotein APTT Activated Partial Thromboplastin Time PT Prothrombin Time BCLC Barcelona Clinic Liver Cancer ECOG Eastern Cooperative Oncology Group AE Adverse Event SAE Severe Adverse Event VEGF Vascular Endothelial Growth Factor HIF-1α Hypoxia-Inducible Factor 1α HR Hazard Ratio CI Confidence Interval OR Odds Ratio SD Standard Deviation IQR Interquartile Range N/A Not Applicable Declarations Author Contribution Huyu Jiao, Xinmei Yan, Junxin Li , and Zhengang Zhang conceived and designed the study. Huyu Jiao, Xinmei Yan, and Junxin Li collected and assembled the data. Huyu Jiao analyzed the data and wrote the article. Xinmei Yan, Junxin Li , and Zhengang Zhang helped to review the article critically. All authors contributed to data analysis, drafting or revising the article, have agreed on the journal to which the article will be submitted, and agree to be accountable for all aspects of the work. Data Availability The datasets used and/or analysed during the current study available from the corresponding author on reasonable request. References Li, C. & He, W. Q. Comparison of primary liver cancer mortality estimates from World Health Organization, global burden disease and global cancer observatory. Liver Int. 42 , 2299–2316 (2022). Wang, C. & Li, S. Clinical characteristics and prognosis of 2887 patients with hepatocellular carcinoma: A single center 14 years experience from China. Medicine 98 , e14070 (2019). Reig, M. & Bruix, J. Reply to: Correspondence on the . J. Hepatol. 76 , 1240–1241 (2022). Wang, L. et al. Enhanced interactions within microenvironment accelerates dismal prognosis in HBV-related HCC after TACE. Hepatol. Commun. 8 , e0548 (2024). Philips, G. K. & Atkins, M. Therapeutic uses of anti-PD-1 and anti-PD-L1 antibodies. Int. Immunol. 27 , 39–46 (2015). Xie, F., Xu, M., Lu, J., Mao, L. & Wang, S. The role of exosomal PD-L1 in tumor progression and immunotherapy. Mol. Cancer . 18 , 146 (2019). Llovet, J. M. et al. Locoregional therapies in the era of molecular and immune treatments for hepatocellular carcinoma. Nat. Rev. Gastroenterol. Hepatol. 18 , 293–313 (2021). Zhu, H. D. et al. Transarterial chemoembolization with PD-(L)1 inhibitors plus molecular targeted therapies for hepatocellular carcinoma (CHANCE001). Sig Transduct. Target. Ther. 8 , 1–10 (2023). Zhou, J. et al. Guidelines for the Diagnosis and Treatment of Primary Liver Cancer (2022 Edition). Liver Cancer . 12 , 405–444 (2023). Zhong, B. et al. Transarterial chemoembolization refractoriness in hepatocellular carcinoma: Chinese College of Interventionalists definition and consensus statement. Chin. Med. J. 137 , 2040 (2024). Aoki, T. et al. Narrow-band Imaging Examination of Microvascular Architecture of Subcapsular Hepatic Tumors. J. Surg. Res. 261 , 51–57 (2021). Choi, J. Y., Lee, J. M. & Sirlin, C. B. CT and MR Imaging Diagnosis and Staging of Hepatocellular Carcinoma: Part I. Development, Growth, and Spread: Key Pathologic and Imaging Aspects. Radiology 272 , 635–654 (2014). Chen, L. et al. Development of TACE Refractoriness Scores in Hepatocellular Carcinoma. Front. Mol. Biosci. 8 , (2021). Kudo, M. et al. A Changing Paradigm for the Treatment of Intermediate-Stage Hepatocellular Carcinoma: Asia-Pacific Primary Liver Cancer Expert Consensus Statements. Liver Cancer . 9 , 245–260 (2020). Guo, X. et al. Multiparametric MRI-based radiomics and clinical nomogram predicts the recurrence of hepatocellular carcinoma after postoperative adjuvant transarterial chemoembolization. BMC Cancer . 25 , 1–12 (2025). Xu, B. et al. Tumor Radiomic Features on Pretreatment MRI to Predict Response to Lenvatinib plus an Anti-PD-1 Antibody in Advanced Hepatocellular Carcinoma: A Multicenter Study. Liver Cancer . 12 , 262–276 (2022). Mao, S. et al. A new prognostic model predicting hepatocellular carcinoma early recurrence in patients with microvascular invasion who received postoperative adjuvant transcatheter arterial chemoembolization. Eur. J. Surg. Oncol. 49 , 129–136 (2023). European Association for the Study of the Liver. EASL Clinical Practice Guidelines: Management of hepatocellular carcinoma. J. Hepatol. 69 , 182–236 (2018). Moustafa, A. S. et al. Chemoembolization of Hepatocellular Carcinoma with Extrahepatic Collateral Blood Supply: Anatomic and Technical Considerations. RadioGraphics 37, 963–977 (2017). Shinkawa, H. et al. The Prognostic Impact of Tumor Differentiation on Recurrence and Survival after Resection of Hepatocellular Carcinoma Is Dependent on Tumor Size. Liver Cancer . 10 , 461–472 (2021). Wu, H. et al. Next-Generation Flexible Embolic Systems: Targeted Transarterial Chemoembolization Strategies for Hepatocellular Carcinoma. Adv Mater e2503971 (2025). 10.1002/adma.202503971 Gk, A. A. TACE and sorafenib: a good marriage? J. Clin. oncology: official J. Am. Soc. Clin. Oncol. 29 , (2011). Yamauchi, M. et al. Lenvatinib activates anti-tumor immunity by suppressing immunoinhibitory infiltrates in the tumor microenvironment of advanced hepatocellular carcinoma. Commun. Med. (Lond) . 3 , 152 (2023). Zhao, Y., Zhang, Y. N., Wang, K. T. & Chen, L. Lenvatinib for hepatocellular carcinoma: From preclinical mechanisms to anti-cancer therapy. Biochim. Biophys. Acta Rev. Cancer . 1874 , 188391 (2020). Xing, R., Gao, J., Cui, Q. & Wang, Q. Strategies to Improve the Antitumor Effect of Immunotherapy for Hepatocellular Carcinoma. Front. Immunol. 12 , (2021). Butte, M. J., Keir, M. E., Phamduy, T. B., Sharpe, A. H. & Freeman, G. J. Programmed death-1 ligand 1 interacts specifically with the B7-1 costimulatory molecule to inhibit T cell responses. Immunity 27 , 111–122 (2007). Hack, S. P., Zhu, A. X. & Wang, Y. Augmenting Anticancer Immunity Through Combined Targeting of Angiogenic and PD-1/PD-L1 Pathways: Challenges and Opportunities. Front. Immunol. 11 , (2020). Jiang, J. et al. The immune-reinforcements of Lenvatinib plus anti-PD-1 and their rationale to unite with TACE for unresectable hepatocellular carcinoma treatment. Immunol. Lett. 275 , 107003 (2025). Huang, J. X. et al. A Study on Overcoming Post-TACE Drug Resistance in HCC Based on Controllable Oxygen Release-Magnetic Hyperthermia Therapy. Adv. Healthc. Mater. e2402253 10.1002/adhm.202402253 (2024). Wang, Z., Li, Q. & Liang, B. Hypoxia as a Target for Combination with Transarterial Chemoembolization in Hepatocellular Carcinoma. Pharmaceuticals 17 , 1057 (2024). Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted 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. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6558171","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":498235663,"identity":"0b5e4173-d560-4d53-8dd7-3e9bf9c99960","order_by":0,"name":"Huyu Jiao","email":"","orcid":"","institution":"Tongji Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology","correspondingAuthor":false,"prefix":"","firstName":"Huyu","middleName":"","lastName":"Jiao","suffix":""},{"id":498235666,"identity":"1782e578-164f-4daf-8aa0-7fffa5f66023","order_by":1,"name":"Xinmei Yan","email":"","orcid":"","institution":"Tongji Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology","correspondingAuthor":false,"prefix":"","firstName":"Xinmei","middleName":"","lastName":"Yan","suffix":""},{"id":498235668,"identity":"df52df92-c741-43eb-8408-131c48801dad","order_by":2,"name":"Junxin Li","email":"","orcid":"","institution":"Tongji Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology","correspondingAuthor":false,"prefix":"","firstName":"Junxin","middleName":"","lastName":"Li","suffix":""},{"id":498235672,"identity":"846b41e2-1363-4dfe-a90b-486d70275ec6","order_by":3,"name":"Zhengang Zhang","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABAklEQVRIiWNgGAWjYHACNhAhx8BwBkjxgEUMiNJizAPScoAULYk9IBsOMBChRb5/+bMHP3fUpu9nPHuA+YPMtsQG9uZtEgw1d3BqYZzxIN2w98zx3B6GcwlAh91ObOA5VibBcOwZTi3MEgeOSfC2HQNqOWMA0SKRYybB2HAYt0ckDrZJ/m07ls4D1yL/Br8WHv5mNmnetpoEhBYJHvxaJCTY2KRl2w4Y9hw4Y3DgDM9t4zaetGKLhGO4tcj3H38m+batTp59xhnDB5U9t2X72Q9vvPGhBrcWBokEEAlUIHGA4QBjDzSaEnBrYGDgPwAi64CMBiD9A5/SUTAKRsEoGKkAAOilWOm3fbmfAAAAAElFTkSuQmCC","orcid":"","institution":"Tongji Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology","correspondingAuthor":true,"prefix":"","firstName":"Zhengang","middleName":"","lastName":"Zhang","suffix":""}],"badges":[],"createdAt":"2025-04-29 16:08:04","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6558171/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6558171/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":88982955,"identity":"0d441747-059c-49f4-82e3-b616eb126c90","added_by":"auto","created_at":"2025-08-13 11:56:42","extension":"jpeg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":112676,"visible":true,"origin":"","legend":"\u003cp\u003ePatient Recruitment Flowchart for This Study\u003c/p\u003e","description":"","filename":"floatimage1.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-6558171/v1/ffde5bb6c24d373299d0af10.jpeg"},{"id":88982961,"identity":"785c2aa8-dddb-482c-b943-71e46497ec6c","added_by":"auto","created_at":"2025-08-13 11:56:42","extension":"jpeg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":39563,"visible":true,"origin":"","legend":"\u003cp\u003eFrequency of TACE Procedures in Combination Therapy Group vs. Monotherapy Group\u003c/p\u003e","description":"","filename":"floatimage2.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-6558171/v1/b7c50fdbe813befa0ecfa3ac.jpeg"},{"id":88983560,"identity":"c971ae1a-4257-41dc-87e6-723b1ab18adf","added_by":"auto","created_at":"2025-08-13 12:04:42","extension":"jpeg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":310838,"visible":true,"origin":"","legend":"\u003cp\u003eKaplan-Meier Analysis of Progression-Free Survival (PFS) (a) and Overall Survival (OS) (b)\u003c/p\u003e","description":"","filename":"floatimage3.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-6558171/v1/24a8a539517b6997fa44a37d.jpeg"},{"id":89487922,"identity":"62bd7b16-2f68-4b30-bdea-1d632bd8bfe0","added_by":"auto","created_at":"2025-08-20 13:09:29","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1340094,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6558171/v1/d1e0e59e-75b0-4ad9-a721-c68bb5a9eac6.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"TACE Combined with PD-L1 Inhibitors Effectively Mitigates TACE Resistance in Advanced Hepatocellular Carcinoma: A Propensity Score-Matched Study","fulltext":[{"header":"Introduction","content":"\u003cp\u003ePrimary liver cancer, a frequently occurring malignancy, currently ranks sixth in global cancer incidence and third in cancer-related mortality \u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u003c/sup\u003e.Unfortunately, most patients are diagnosed at advanced stages, missing the optimal window for surgical intervention, leading to poor prognosis \u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e.For advanced HCC, transarterial chemoembolization (TACE) remains the primary treatment modality \u003csup\u003e\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u003c/sup\u003e. However, a significant proportion of undifferentiated HCC (uHCC) patients experience disease progression within one year of TACE treatment. This progression is associated with enhanced interactions within the tumor microenvironment post-TACE, potentially contributing to post-treatment deterioration \u003csup\u003e\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u003c/sup\u003e. Clinical studies have shown that immunotherapies, including PD-1 and PD-L1 inhibitors, exhibit promising efficacy and safety profiles in phase I and II trials for advanced HCC \u003csup\u003e\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e,\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u003c/sup\u003e.Consequently, combining TACE with immunotherapy may achieve synergistic effects, potentially enhancing therapeutic outcomes. The primary mechanism underlying this combination involves TACE-induced antigen release and upregulation of PD-L1 expression, fostering an immunosuppressive microenvironment that augments responsiveness to PD-L1 inhibitors \u003csup\u003e\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u003c/sup\u003e. Numerous studies have confirmed that TACE combined with PD-(L)1 blockade and MTT significantly improves PFS, OS, and ORR in Chinese patients with advanced HCC, with acceptable safety profiles \u003csup\u003e\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u003c/sup\u003e.This study further substantiates the beneficial role of TACE combined with PD-(L)1 inhibitors and MTT in mitigating TACE resistance in advanced HCC.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003e This study strictly adhered to the guidelines outlined in the Declaration of Helsinki and received formal approval from the Ethics Committee of Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology (Ethics Approval Number: TJ-IRB202412142). Given the retrospective nature of the study, written informed consent was waived. The study design was based on the \"Chinese Guidelines for the Diagnosis and Treatment of Primary Liver Cancer\" and targeted patients clinically or pathologically diagnosed with HCC \u003csup\u003e\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u003c/sup\u003e.Patient data were collected between January 2020 and December 2024, including those who underwent TACE or TACE combined with PD-(L)1 inhibitors and MTT at our institution. Inclusion criteria were as follows:\u003c/p\u003e\u003cp\u003e(1) Aged\u0026thinsp;\u0026ge;\u0026thinsp;18 years;\u003c/p\u003e\u003cp\u003e(2) Barcelona Clinic Liver Cancer (BCLC) stage B or C HCC;\u003c/p\u003e\u003cp\u003e(3) Received at least three cycles of TACE alone or TACE combined with PD-(L)1 inhibitors and MTT (defined as concurrent or sequential TACE and PD-(L)1 inhibitor administration within 60 days, combined with MTT);\u003c/p\u003e\u003cp\u003e(4) Child-Pugh class A or B liver function;\u003c/p\u003e\u003cp\u003e(5) Eastern Cooperative Oncology Group (ECOG) performance status score of 0\u0026ndash;1;\u003c/p\u003e\u003cp\u003e(6) Presence of at least one measurable target lesion assessable by Response Evaluation Criteria in Solid Tumors (RECIST).\u003c/p\u003e\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003eExclusion criteria included:\u003c/h2\u003e\u003cp\u003e(1) Patients with other primary malignancies;\u003c/p\u003e\u003cp\u003e(2) Patients receiving treatment regimens outside the study protocols;\u003c/p\u003e\u003cp\u003e(3) Patients lost to follow-up or with incomplete medical records.\u003c/p\u003e\u003c/div\u003e\n\u003ch3\u003eTreatment Protocols\u003c/h3\u003e\n\u003cp\u003e\u003cstrong\u003eTACE Treatment\u003c/strong\u003e\u003cp\u003eTACE was typically administered prior to the initiation of PD-L1 inhibitor therapy. During the procedure, patients received local anesthesia, followed by catheterization of the celiac trunk or superior mesenteric artery via a 5-French catheter, and subsequent angiography. A 2.7 French microcatheter was then navigated into the specific artery supplying the tumor. A mixture of 20 mg pirarubicin and 10 mL lipiodol was injected for embolization, followed by additional embolization using gelatin sponge particles until complete cessation of blood flow in the tumor-feeding artery was achieved.\u003c/p\u003e\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eAnti-PD-(L)1 Drugs\u003c/strong\u003e\u003cp\u003e For patients receiving TACE combined with PD-(L)1 inhibitors and MTT, various PD-(L)1 inhibitors were selected based on treatment guidelines and drug availability in the Chinese market, including sintilimab, tislelizumab, and pembrolizumab. All selected PD-(L)1 inhibitors were administered according to their standard dosages and frequencies.\u003c/p\u003e\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eMolecular Targeted Therapy\u003c/strong\u003e\u003cp\u003eFor patients receiving TACE combined with PD-(L)1 inhibitors and MTT, various molecular targeted drugs were employed, including sorafenib, lenvatinib, apatinib, and bevacizumab (an anti-VEGF agent). All medications were initiated within two weeks post-TACE.\u003c/p\u003e\u003c/p\u003e\n\u003ch3\u003eFollow-Up and Assessment\u003c/h3\u003e\n\u003cp\u003eAll patients underwent computed tomography (CT) and/or magnetic resonance imaging (MRI), liver function tests, complete blood counts, and tumor marker assessments within 1\u0026ndash;3 months following each TACE session. TACE efficacy was evaluated using dynamic CT/MRI, and patients were categorized as having complete response (CR), partial response (PR), stable disease (SD), or progressive disease (PD) according to modified RECIST (mRECIST) criteria. Patients with PR, SD, or PD underwent subsequent TACE or TACE combined with PD-(L)1 inhibitors and MTT. The occurrence of TACE resistance was determined 1\u0026ndash;3 months after three consecutive standardized and refined TACE sessions, based on enhanced CT/MRI findings indicating persistent disease progression (PD) of intrahepatic target lesions compared to baseline assessments, as per the Chinese definition of TACE resistance \u003csup\u003e\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e\u003cdiv id=\"Sec6\" class=\"Section2\"\u003e\u003ch2\u003eStatistical Analysis\u003c/h2\u003e\u003cp\u003eTo control for confounding factors, 1:1 nearest-neighbor propensity score matching (PSM) was employed with a caliper width of 0.02 to ensure matching quality. Covariate balance was assessed using standardized mean differences (SMD), with a threshold of \u0026lt;\u0026thinsp;0.1 indicating adequate balance. Continuous variables were compared using independent samples t-tests (for normally distributed data, reported as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation) or Mann-Whitney U tests (for non-normally distributed data, reported as median\u0026thinsp;\u0026plusmn;\u0026thinsp;interquartile range). Categorical variables were analyzed using chi-square tests or Fisher's exact tests. Cox proportional hazards models were used to identify risk factors associated with TACE resistance (variables with p\u0026thinsp;\u0026lt;\u0026thinsp;0.05 in univariate analysis were entered into multivariate analysis). Kaplan-Meier methods were used to plot OS and PFS curves. All analyses were performed using R (version 4.2.2) and SPSS (version 27.0). Two-tailed p-values\u0026thinsp;\u0026lt;\u0026thinsp;0.05 were considered statistically significant. The proportional hazards assumption for the Cox model and the statistical power of the matched sample size were verified.\u003c/p\u003e\u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e\u003ch2\u003ePatient Baseline Characteristics\u003c/h2\u003e\u003cp\u003e We systematically reviewed clinical data of HCC patients treated at our institution between January 2020 and December 2024. Patients who underwent at least three consecutive TACE sessions, either alone or in combination with PD-(L)1 inhibitors and MTT, were included. After rigorous screening, 604 eligible patients were identified, comprising 532 who received TACE alone and 72 who received combination therapy(Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Baseline characteristic analysis revealed that the combination therapy group exhibited greater tumor burden (mean maximum tumor diameter: 9.15 cm vs. 6.60 cm, p\u0026thinsp;=\u0026thinsp;0.001) and a higher incidence of portal vein tumor thrombus (41.7% vs. 23.3%, p\u0026thinsp;=\u0026thinsp;0.001). To minimize confounding, 1:1 PSM was performed, resulting in a balanced cohort of 144 patients (72 pairs). Post-matching, both groups were comparable in terms of male predominance, viral hepatitis history, and mean maximum tumor diameter (8.0 cm). No statistically significant differences were observed in any clinicopathological parameters between the groups (p\u0026thinsp;\u0026gt;\u0026thinsp;0.05) (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e\u003cp\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 patients in combination therapy group and monotherapy group before and after PSM.\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=\"char\" char=\".\" 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=\"char\" char=\".\" 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\" colname=\"c2\"\u003e\u003cp\u003e0 N\u0026thinsp;=\u0026thinsp;532\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1 N\u0026thinsp;=\u0026thinsp;72\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003ep.overall\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0 N\u0026thinsp;=\u0026thinsp;72\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\u003e\u003cp\u003e1 N\u0026thinsp;=\u0026thinsp;72\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c7\"\u003e\u003cp\u003ep.overall\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eGender:\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.882\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=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e0.325\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ewemen\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e59 (11.1%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e7 (9.72%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e12 (16.7%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e7 (9.72%)\u003c/p\u003e\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\u003eman\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e473 (88.9%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e65 (90.3%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e60 (83.3%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e65 (90.3%)\u003c/p\u003e\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\u003eAge\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e54.9 (10.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e56.2 (10.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.330\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e58.3 (11.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e56.2 (10.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e0.250\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eComorbid Hepatitis B\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.184\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=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e0.669\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNo\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e75 (14.1%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e15 (20.8%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e12 (16.7%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e15 (20.8%)\u003c/p\u003e\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\u003eYes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e457 (85.9%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e57 (79.2%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e60 (83.3%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e57 (79.2%)\u003c/p\u003e\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\u003eWhite Blood Cells\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e5.23 [3.79;6.51]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e5.67 [4.38;6.77]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.094\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e5.88 [4.11;7.71]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e5.67 [4.38;6.77]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e0.453\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eLymphocytes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.19 [0.87;1.59]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1.31 [1.07;1.68]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.031\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e1.23 [0.89;1.56]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e1.31 [1.07;1.68]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e0.128\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHemoglobin\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e133 [120;147]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e138 [124;148]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.304\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e132 [119;142]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e138 [124;148]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e0.169\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePlatelets\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e128 [80.2;190]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e180 [130;226]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e154 [102;222]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e180 [130;226]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e0.110\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAlbumin\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e38.6 [34.9;42.2]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e38.7 [36.3;41.7]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.583\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e38.0 [35.5;42.0]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e38.7 [36.3;41.7]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e0.460\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eALT\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e33.0 [23.0;52.0]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e36.5 [22.0;54.2]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.980\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e33.0 [20.8;48.0]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e36.5 [22.0;54.2]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e0.616\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAST\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e44.0 [31.0;69.0]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e53.5 [32.8;92.8]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.046\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e47.0 [30.8;79.2]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e53.5 [32.8;92.8]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e0.306\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTotal_Bilirubin\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e14.9 [9.88;22.1]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e15.3 [11.5;21.1]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.475\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e14.4 [10.0;20.3]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e15.3 [11.5;21.1]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e0.361\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAFP\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.826\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=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e0.170\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u0026lt;400\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e307 (57.7%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e40 (55.6%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e49 (68.1%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e40 (55.6%)\u003c/p\u003e\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\u003e\u0026ge;\u0026thinsp;400\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e225 (42.3%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e32 (44.4%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e23 (31.9%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e32 (44.4%)\u003c/p\u003e\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\u003eAPTT\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e38.5 [35.8;41.4]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e36.0 [34.6;38.8]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e38.1 [33.8;39.5]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e36.0 [34.6;38.8]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e0.230\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePT\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e14.1 [13.5;15.2]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e13.3 [12.7;13.9]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e13.4 [12.8;14.3]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e13.3 [12.7;13.9]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e0.160\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eFibrinogen\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e3.04 [2.45;3.95]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e3.61 [2.91;4.54]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e3.43 [2.74;4.33]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e3.61 [2.91;4.54]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e0.501\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePrimary Tumor Size\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e66.0 [37.8;100]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e91.5 [57.5;122]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e85.0 [42.5;120]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e91.5 [57.5;122]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e0.370\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNumber of Tumors\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.192\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=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e0.577\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNo\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e178 (33.5%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e18 (25.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e22 (30.6%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e18 (25.0%)\u003c/p\u003e\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\u003eYes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e354 (66.5%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e54 (75.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e50 (69.4%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e54 (75.0%)\u003c/p\u003e\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\u003eTumor Capsule:\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.130\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=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e0.489\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNo\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e163 (30.6%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e29 (40.3%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e24 (33.3%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e29 (40.3%)\u003c/p\u003e\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\u003eYes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e369 (69.4%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e43 (59.7%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e48 (66.7%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e43 (59.7%)\u003c/p\u003e\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\u003eTumor Thrombus:\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.001\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=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e0.225\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNo\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e408 (76.7%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e42 (58.3%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e50 (69.4%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e42 (58.3%)\u003c/p\u003e\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\u003eYes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e124 (23.3%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e30 (41.7%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e22 (30.6%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e30 (41.7%)\u003c/p\u003e\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\u003eBilobar Distribution of Tumor\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.446\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=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e0.867\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNo\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e320 (60.2%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e39 (54.2%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e37 (51.4%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e39 (54.2%)\u003c/p\u003e\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\u003eYes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e212 (39.8%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e33 (45.8%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e35 (48.6%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e33 (45.8%)\u003c/p\u003e\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\u003eChild Pugh Classification\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\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=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e0.366\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e488 (91.7%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e71 (98.6%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.098\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e69 (95.8%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e71 (98.6%)\u003c/p\u003e\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\u003eB\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e44 (8.3%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1 (1.4%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e3 (4.2%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e1 (1.4%)\u003c/p\u003e\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\u003ePerformance Status Score\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\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=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e1.000\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e456 (85.7%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e60 (83.3%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.719\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e61 (84.7%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e60 (83.3%)\u003c/p\u003e\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\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e76 (14.3%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e12 (16.7%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e11 (15.3%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e12 (16.7%)\u003c/p\u003e\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\u003eBCLC:\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\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=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e0.580\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eB\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e304 (57.2%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e32 (44.4%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.042\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e34 (47.2%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e32 (44.4%)\u003c/p\u003e\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\u003eC\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e228 (42.8%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e40 (53.6%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e38 (52.8%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e40 (53.6%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003c/div\u003e\n\u003ch3\u003eClinical Outcomes\u003c/h3\u003e\n\u003cp\u003eAll patients received three consecutive refined treatment cycles. Tumor progression was compared between the TACE-PD-(L)1-MTT combination group and the TACE monotherapy group. TACE resistance occurred in only 7 patients (9.7%) in the combination group, compared to 28 patients (38.8%) in the monotherapy group (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). This difference was statistically significant (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), indicating superior tumor progression control with combination therapy. Furthermore, the median follow-up durations were comparable between the combination and monotherapy groups (14.8 months [IQR 10.4\u0026ndash;20.6] vs. 15.3 months [IQR 9.2\u0026ndash;21.9], p\u0026thinsp;=\u0026thinsp;0.23). Survival analysis demonstrated significant benefits with combination therapy: median PFS (mPFS) was 17.5 months (95% CI 15.7\u0026ndash;19.3) in the combination group, an 8.4-month improvement over the monotherapy group's mPFS of 9.1 months (95% CI 6.2\u0026ndash;12.2, p\u0026thinsp;=\u0026thinsp;0.004) (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). Median OS (mOS) reached 20.8 months in the combination group compared to 16.4 months (95% CI 11.3\u0026ndash;21.5) in the monotherapy group, with a statistically significant difference (p\u0026thinsp;=\u0026thinsp;0.0084). These data underscore the substantial advantages of combination therapy in prolonging PFS and OS. Finally, we analyzed risk factors for TACE resistance in 532 patients who developed resistance after TACE monotherapy. Univariate and multivariate logistic regression identified bilobar tumor distribution, maximum tumor diameter, and tumor capsule absence as independent risk factors for TACE resistance (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eUnivariate and Multivariate Analysis of TACE Resistance\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 logistic regression analysis\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colspan=\"3\" nameend=\"c7\" namest=\"c5\"\u003e\u003cp\u003eMultivariate logistic regression analysis\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003echaracteristics\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eOR\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eCI\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eP\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eOR\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eCI\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eP\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAge\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\u003e0.97-1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.128\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\u003eFemale\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.15\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.59\u0026ndash;2.24\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.687\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\u003eComorbid Hepatitis B\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\u003e0.56\u0026ndash;2.01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.858\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\u003eWhite Blood Cells\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.13\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1.04\u0026ndash;1.24\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.005\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\u003e0.95\u0026ndash;1.22\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.09\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eLymphocytes\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\u003e0.95\u0026ndash;1.12\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.445\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\u003eHemoglobin\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.12\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.99\u0026ndash;1.21\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.96\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\u003ePlatelets\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.23\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1-1.41\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.53\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\u003eAlbumin\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.02\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.98\u0026ndash;1.06\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.361\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\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\u003e1.21\u0026ndash;1.65\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.67\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\u003eAST\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.55\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1.32\u0026ndash;1.75\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.819\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\u0026thinsp;\u0026ge;\u0026thinsp;400\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2.07\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1.34\u0026ndash;3.19\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e1.92\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e1.42\u0026ndash;2.95\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\u003eAPTT\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\u003e0.96\u0026ndash;1.07\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.94\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\u003ePT\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.91\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.79\u0026ndash;1.04\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.177\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\u003eFibrinogen\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.36\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1.15\u0026ndash;1.61\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.23\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\u003ePrimary Tumor size\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1.01\u0026ndash;1.02\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u0026lt;0.001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e1.01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e1-1.02\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNumber of multiple tumors\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.96\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1.21\u0026ndash;3.18\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.006\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\u003eTumor Capsule\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.18\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.11\u0026ndash;0.29\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u0026lt;0.001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.29\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.17\u0026ndash;0.48\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.002\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTumor Thrombus\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e4.52\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e2.74\u0026ndash;7.47\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.03\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\u003eBilobar Distribution of Tumor\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2.46\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1.59\u0026ndash;3.8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u0026lt;0.001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e2.13\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e1.3\u0026ndash;3.48\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.003\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eChild Pugh Classification B\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2.25\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1.1\u0026ndash;4.62\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.027\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e2.14\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e1.23\u0026ndash;4.21\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.07\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBCLC-B\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2.56\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.92\u0026ndash;7.14\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.073\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\u003eBCLC-C\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e6.9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e2.39\u0026ndash;19.92\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\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\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\n\u003ch3\u003eSafety Analysis\u003c/h3\u003e\n\u003cp\u003eAfter PSM, 48 of 72 patients (66.6%) in the combination group reported adverse events (AEs), compared to 35 of 72 patients (48.6%) in the monotherapy group (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). Grade 3 or higher severe AEs (SAEs) occurred in 19.4% (combination group, 14 cases) and 9.7% (monotherapy group, 7 cases) of patients. No grade 5 life-threatening or fatal AEs were observed in either group. In the combination group, 5 patients (6.9%) required temporary discontinuation of lenvatinib due to treatment-related AEs, and 12 patients (16.6%) needed dose adjustments for PD-(L)1 immune checkpoint inhibitors and molecular targeted drugs. However, no patients discontinued treatment. All AEs were effectively managed through clinical interventions, and no treatment discontinuations or deaths occurred due to AEs.\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 3\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eAny-Cause Adverse Events in Combination Group vs. Monotherapy Group After PSM\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"3\"\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\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\u003eCombination group (\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;72)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eMonotherapy group (\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;72)\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePatients with an adverse event from any cause\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e48 (66.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e35 (48.6)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eGrade 1 or 2 event\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e34 (47.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e28 (38.9)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eGrade 3 event\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e12 (16.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e7 (9.7)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eGrade 4 event\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2 (2.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eGrade 5 event\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDose interruption of anti-PD-(L)1 therapies\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e5 (6.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eN/A\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDose reduction or interruption of molecular targeted therapies\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e12 (16.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eN/A\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis study innovatively demonstrates that the combination of TACE with PD-(L)1 immune checkpoint inhibitors and MTT significantly reverses treatment resistance observed after three TACE cycles. In the core efficacy comparison, only 7 patients (9.7%) in the combination group exhibited target lesion progression, compared to 28 patients (38.8%) in the TACE monotherapy group, with a statistically significant difference (p\u0026thinsp;\u0026lt;\u0026thinsp;0.01). Survival analysis further revealed a more favorable disease control trend with combination therapy, as evidenced by significantly superior PFS and OS compared to monotherapy. These findings strongly align with the recently published CHANCE001 multicenter retrospective study. This national cohort study (n\u0026thinsp;=\u0026thinsp;867) demonstrated that TACE combined with PD-(L)1 inhibitors and MTT provides triple clinical benefits for advanced HCC patients: a 1.5-month prolongation of median PFS (HR\u0026thinsp;=\u0026thinsp;0.76, p\u0026thinsp;=\u0026thinsp;0.015), a 3.5-month prolongation of median OS (HR\u0026thinsp;=\u0026thinsp;0.76, p\u0026thinsp;=\u0026thinsp;0.001), and an increased ORR of 28.1% \u003csup\u003e8\u003c/sup\u003e.Notably, this study transcends traditional PFS definitions by innovatively focusing on intrahepatic target lesion progression as the primary endpoint, while considering new lesions, portal vein invasion, and extrahepatic metastases as secondary indicators. This evaluation framework more precisely reflects the biological characteristics of TACE resistance and offers clinically relevant insights for therapeutic assessment.\u003c/p\u003e\u003cp\u003eFurthermore, this study identifies three core biological drivers of TACE resistance in advanced HCC: maximum tumor diameter, absence of tumor capsule integrity, and bilobar infiltrative growth. These indicators not only serve as independent prognostic markers but also represent critical targets for personalized treatment strategies. From a tumor biological perspective, the absence of tumor capsule integrity constitutes a significant warning signal. The pathological mechanism involves the tumor capsule acting as a natural barrier; its disruption enables tumor cells to breach fibrous matrix constraints and infiltrate along portal vein branches. This infiltrative growth pattern simultaneously compromises the integrity of tumor vascular architecture, promoting the formation of abnormal vascular networks between intra- and extra-tumoral vessels \u003csup\u003e\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u003c/sup\u003e.Clinical research confirms that such vascular remodeling significantly increases the risk of portal vein tumor thrombus formation, which represents an important anatomical basis for TACE treatment failure \u003csup\u003e\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u003c/sup\u003e. The prognostic value of bilobar infiltrative growth is validated in this study, aligning with Chen et al.'s meta-analysis of 1,238 patients \u003csup\u003e\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u003c/sup\u003e.The mechanism may involve enhanced intrahepatic metastatic potential of tumor cells, leading to multicentric lesion formation and significantly increasing treatment coverage challenges \u003csup\u003e\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u003c/sup\u003e. Maximum tumor diameter, established as an independent predictor of early TACE refractoriness, receives robust support in this study. Multiple investigations indicate that tumor size represents a critical prognostic factor in HCC patients \u003csup\u003e\u003cspan additionalcitationids=\"CR16\" citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u003c/sup\u003e. Larger tumor diameters (\u0026ge;\u0026thinsp;5 cm) correlate with higher tumor burdens, rendering complete TACE coverage technically challenging \u003csup\u003e\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u003c/sup\u003e. Studies demonstrate that TACE-treated target lesions frequently develop compensatory blood supply through hepatofugal collateral arteries (e.g., inferior phrenic arteries, intercostal arteries) \u003csup\u003e\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e\u003c/sup\u003e. When the tumor diameter exceeds 5 cm, the incidence of extrahepatic collateral arterial supply increases significantly, which directly compromises therapeutic efficacy and is closely associated with treatment failure and poor prognosis \u003csup\u003e\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e,\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e\u003c/sup\u003e.These findings carry important clinical implications: for advanced HCC patients exhibiting these high-risk biological characteristics, early combination with systemic therapies (e.g., immuno-oncology combinations) or localized treatment escalation (e.g., embolic agents) should be considered \u003csup\u003e\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e\u003c/sup\u003e.This precision medicine approach, guided by tumor biological features, has the potential to overcome traditional TACE limitations and substantially improve patient outcomes.\u003c/p\u003e\u003cp\u003eThe remarkable efficacy observed in the combination therapy group can be attributed to multi-mechanistic synergies. TACE induces ischemic necrosis by embolizing tumor-feeding arteries while locally releasing chemotherapeutic agents to enhance cytotoxic effects. However, the hypoxic microenvironment in residual tumor cells post-TACE triggers VEGF upregulation, stimulating tumor angiogenesis and serving as a pathophysiological basis for disease progression \u003csup\u003e\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e\u003c/sup\u003e.Molecular targeted agents (e.g., lenvatinib, sorafenib) effectively block TACE-induced tumor vascular regeneration by inhibiting VEGF receptor signaling pathways, thereby delaying recurrence \u003csup\u003e\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e,\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e\u003c/sup\u003e.Concurrently, these agents normalize tumor vasculature, significantly optimizing the immune cell infiltration microenvironment and creating favorable conditions for immune checkpoint inhibitor efficacy \u003csup\u003e\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e,\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e\u003c/sup\u003e.The PD-1/PD-L1 axis plays a pivotal role in tumor immune evasion. Activation of this pathway suppresses T-cell activity, enabling tumor cells to evade immune surveillance \u003csup\u003e\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e\u003c/sup\u003e. PD-(L)1 inhibitors restore T-cell cytotoxic function by blocking inhibitory signals, thereby eliciting anti-tumor immune responses \u003csup\u003e\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e\u003c/sup\u003e.The triple combination forms a therapeutic loop encompassing \"vascular occlusion, immune activation, and immune enhancement,\" exerting synergistic anti-tumor effects through three dimensions: tumor angiogenesis inhibition, immune microenvironment remodeling, and T-cell functional restoration. This synergy significantly elevates disease control rates \u003csup\u003e\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e,\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e\u003c/sup\u003e.Our study demonstrates that this triple combination substantially reduces target lesion progression post-TACE.\u003c/p\u003e\u003cp\u003eFor patients experiencing TACE resistance, treatment strategies require dynamic adjustment. Emerging research suggests targeting the hypoxic microenvironment with hypoxia-activated prodrugs (e.g., APX005M) or HIF-1α inhibitors may partially reverse TACE resistance \u003csup\u003e\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e,\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e\u003c/sup\u003e.However, standardized post-TACE resistance treatment protocols remain undefined, necessitating prospective studies to explore personalized therapeutic regimens.\u003c/p\u003e\u003cp\u003eThis study has several limitations. The retrospective design carries inherent risks of selection bias, as evidenced by baseline characteristic differences. To mitigate this, we employed PSM and conducted sensitivity analyses commonly used in real-world research. Additionally, the relatively small sample size necessitates larger cohort studies for more in-depth investigations.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eOur study demonstrates the beneficial role of TACE combined with PD-(L)1 immune checkpoint inhibitors and MTT in mitigating TACE resistance in advanced HCC. Furthermore, it identifies maximum tumor diameter, bilobar infiltrative growth, and multiple tumor lesions as independent risk factors. These findings provide novel theoretical frameworks and practical directions for optimizing treatment strategies in patients with TACE resistance.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cdiv class=\"DefinitionList\"\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eTACE\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eTransarterial Chemoembolization\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003ePD-(L)1\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eProgrammed Death-Ligand 1\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eMTT\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eMolecular Targeted Therapies\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eHCC\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eHepatocellular Carcinoma\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003ePFS\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eProgression-Free Survival\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eOS\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eOverall Survival\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eORR\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eObjective Response Rate\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003ePSM\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003ePropensity Score Matching\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eRECIST\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eResponse Evaluation Criteria in Solid Tumors\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003emRECIST\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eModified RECIST\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eCT\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eComputed Tomography\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eMRI\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eMagnetic Resonance Imaging\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eAFP\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eAlpha-Fetoprotein\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eAPTT\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eActivated Partial Thromboplastin Time\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003ePT\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eProthrombin Time\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eBCLC\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eBarcelona Clinic Liver Cancer\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eECOG\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eEastern Cooperative Oncology Group\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eAE\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eAdverse Event\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eSAE\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eSevere Adverse Event\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eVEGF\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eVascular Endothelial Growth Factor\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eHIF-1α\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eHypoxia-Inducible Factor 1α\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eHR\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eHazard Ratio\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eCI\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eConfidence Interval\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eOR\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eOdds Ratio\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eSD\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eStandard Deviation\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eIQR\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eInterquartile Range\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eN/A\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eNot Applicable\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003c/div\u003e"},{"header":"Declarations","content":"\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eHuyu Jiao, Xinmei Yan, Junxin Li , and Zhengang Zhang conceived and designed the study. Huyu Jiao, Xinmei Yan, and Junxin Li collected and assembled the data. Huyu Jiao analyzed the data and wrote the article. Xinmei Yan, Junxin Li , and Zhengang Zhang helped to review the article critically. All authors contributed to data analysis, drafting or revising the article, have agreed on the journal to which the article will be submitted, and agree to be accountable for all aspects of the work.\u003c/p\u003e\u003ch2\u003eData Availability\u003c/h2\u003e\u003cp\u003eThe datasets used and/or analysed during the current study available from the corresponding author on reasonable request.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eLi, C. \u0026amp; He, W. Q. Comparison of primary liver cancer mortality estimates from World Health Organization, global burden disease and global cancer observatory. \u003cem\u003eLiver Int.\u003c/em\u003e \u003cb\u003e42\u003c/b\u003e, 2299\u0026ndash;2316 (2022).\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eWang, C. \u0026amp; Li, S. Clinical characteristics and prognosis of 2887 patients with hepatocellular carcinoma: A single center 14 years experience from China. \u003cem\u003eMedicine\u003c/em\u003e \u003cb\u003e98\u003c/b\u003e, e14070 (2019).\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eReig, M. \u0026amp; Bruix, J. Reply to: Correspondence on the \u0026lt;\u0026thinsp;BCLC strategy for prognosis prediction and treatment recommendation: The 2022 update\u0026gt;. \u003cem\u003eJ. Hepatol.\u003c/em\u003e \u003cb\u003e76\u003c/b\u003e, 1240\u0026ndash;1241 (2022).\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eWang, L. et al. Enhanced interactions within microenvironment accelerates dismal prognosis in HBV-related HCC after TACE. \u003cem\u003eHepatol. Commun.\u003c/em\u003e \u003cb\u003e8\u003c/b\u003e, e0548 (2024).\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003ePhilips, G. K. \u0026amp; Atkins, M. Therapeutic uses of anti-PD-1 and anti-PD-L1 antibodies. \u003cem\u003eInt. Immunol.\u003c/em\u003e \u003cb\u003e27\u003c/b\u003e, 39\u0026ndash;46 (2015).\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eXie, F., Xu, M., Lu, J., Mao, L. \u0026amp; Wang, S. The role of exosomal PD-L1 in tumor progression and immunotherapy. \u003cem\u003eMol. Cancer\u003c/em\u003e. \u003cb\u003e18\u003c/b\u003e, 146 (2019).\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eLlovet, J. M. et al. Locoregional therapies in the era of molecular and immune treatments for hepatocellular carcinoma. \u003cem\u003eNat. Rev. Gastroenterol. Hepatol.\u003c/em\u003e \u003cb\u003e18\u003c/b\u003e, 293\u0026ndash;313 (2021).\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eZhu, H. D. et al. Transarterial chemoembolization with PD-(L)1 inhibitors plus molecular targeted therapies for hepatocellular carcinoma (CHANCE001). \u003cem\u003eSig Transduct. Target. Ther.\u003c/em\u003e \u003cb\u003e8\u003c/b\u003e, 1\u0026ndash;10 (2023).\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eZhou, J. et al. Guidelines for the Diagnosis and Treatment of Primary Liver Cancer (2022 Edition). \u003cem\u003eLiver Cancer\u003c/em\u003e. \u003cb\u003e12\u003c/b\u003e, 405\u0026ndash;444 (2023).\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eZhong, B. et al. Transarterial chemoembolization refractoriness in hepatocellular carcinoma: Chinese College of Interventionalists definition and consensus statement. \u003cem\u003eChin. Med. J.\u003c/em\u003e \u003cb\u003e137\u003c/b\u003e, 2040 (2024).\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eAoki, T. et al. Narrow-band Imaging Examination of Microvascular Architecture of Subcapsular Hepatic Tumors. \u003cem\u003eJ. Surg. Res.\u003c/em\u003e \u003cb\u003e261\u003c/b\u003e, 51\u0026ndash;57 (2021).\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eChoi, J. Y., Lee, J. M. \u0026amp; Sirlin, C. B. CT and MR Imaging Diagnosis and Staging of Hepatocellular Carcinoma: Part I. Development, Growth, and Spread: Key Pathologic and Imaging Aspects. \u003cem\u003eRadiology\u003c/em\u003e \u003cb\u003e272\u003c/b\u003e, 635\u0026ndash;654 (2014).\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eChen, L. et al. Development of TACE Refractoriness Scores in Hepatocellular Carcinoma. \u003cem\u003eFront. Mol. Biosci.\u003c/em\u003e \u003cb\u003e8\u003c/b\u003e, (2021).\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eKudo, M. et al. A Changing Paradigm for the Treatment of Intermediate-Stage Hepatocellular Carcinoma: Asia-Pacific Primary Liver Cancer Expert Consensus Statements. \u003cem\u003eLiver Cancer\u003c/em\u003e. \u003cb\u003e9\u003c/b\u003e, 245\u0026ndash;260 (2020).\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eGuo, X. et al. Multiparametric MRI-based radiomics and clinical nomogram predicts the recurrence of hepatocellular carcinoma after postoperative adjuvant transarterial chemoembolization. \u003cem\u003eBMC Cancer\u003c/em\u003e. \u003cb\u003e25\u003c/b\u003e, 1\u0026ndash;12 (2025).\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eXu, B. et al. Tumor Radiomic Features on Pretreatment MRI to Predict Response to Lenvatinib plus an Anti-PD-1 Antibody in Advanced Hepatocellular Carcinoma: A Multicenter Study. \u003cem\u003eLiver Cancer\u003c/em\u003e. \u003cb\u003e12\u003c/b\u003e, 262\u0026ndash;276 (2022).\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eMao, S. et al. A new prognostic model predicting hepatocellular carcinoma early recurrence in patients with microvascular invasion who received postoperative adjuvant transcatheter arterial chemoembolization. \u003cem\u003eEur. J. Surg. Oncol.\u003c/em\u003e \u003cb\u003e49\u003c/b\u003e, 129\u0026ndash;136 (2023).\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eEuropean Association for the Study of the Liver. EASL Clinical Practice Guidelines: Management of hepatocellular carcinoma. \u003cem\u003eJ. Hepatol.\u003c/em\u003e \u003cb\u003e69\u003c/b\u003e, 182\u0026ndash;236 (2018).\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eMoustafa, A. S. et al. Chemoembolization of Hepatocellular Carcinoma with Extrahepatic Collateral Blood Supply: Anatomic and Technical Considerations. \u003cem\u003eRadioGraphics\u003c/em\u003e 37, 963\u0026ndash;977 (2017).\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eShinkawa, H. et al. The Prognostic Impact of Tumor Differentiation on Recurrence and Survival after Resection of Hepatocellular Carcinoma Is Dependent on Tumor Size. \u003cem\u003eLiver Cancer\u003c/em\u003e. \u003cb\u003e10\u003c/b\u003e, 461\u0026ndash;472 (2021).\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eWu, H. et al. Next-Generation Flexible Embolic Systems: Targeted Transarterial Chemoembolization Strategies for Hepatocellular Carcinoma. \u003cem\u003eAdv Mater\u003c/em\u003e e2503971 (2025). \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1002/adma.202503971\u003c/span\u003e\u003cspan address=\"10.1002/adma.202503971\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eGk, A. A. TACE and sorafenib: a good marriage? \u003cem\u003eJ. Clin. oncology: official J. Am. Soc. Clin. Oncol.\u003c/em\u003e \u003cb\u003e29\u003c/b\u003e, (2011).\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eYamauchi, M. et al. Lenvatinib activates anti-tumor immunity by suppressing immunoinhibitory infiltrates in the tumor microenvironment of advanced hepatocellular carcinoma. \u003cem\u003eCommun. Med. (Lond)\u003c/em\u003e. \u003cb\u003e3\u003c/b\u003e, 152 (2023).\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eZhao, Y., Zhang, Y. N., Wang, K. T. \u0026amp; Chen, L. Lenvatinib for hepatocellular carcinoma: From preclinical mechanisms to anti-cancer therapy. \u003cem\u003eBiochim. Biophys. Acta Rev. Cancer\u003c/em\u003e. \u003cb\u003e1874\u003c/b\u003e, 188391 (2020).\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eXing, R., Gao, J., Cui, Q. \u0026amp; Wang, Q. Strategies to Improve the Antitumor Effect of Immunotherapy for Hepatocellular Carcinoma. \u003cem\u003eFront. Immunol.\u003c/em\u003e \u003cb\u003e12\u003c/b\u003e, (2021).\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eButte, M. J., Keir, M. E., Phamduy, T. B., Sharpe, A. H. \u0026amp; Freeman, G. J. Programmed death-1 ligand 1 interacts specifically with the B7-1 costimulatory molecule to inhibit T cell responses. \u003cem\u003eImmunity\u003c/em\u003e \u003cb\u003e27\u003c/b\u003e, 111\u0026ndash;122 (2007).\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eHack, S. P., Zhu, A. X. \u0026amp; Wang, Y. Augmenting Anticancer Immunity Through Combined Targeting of Angiogenic and PD-1/PD-L1 Pathways: Challenges and Opportunities. \u003cem\u003eFront. Immunol.\u003c/em\u003e \u003cb\u003e11\u003c/b\u003e, (2020).\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eJiang, J. et al. The immune-reinforcements of Lenvatinib plus anti-PD-1 and their rationale to unite with TACE for unresectable hepatocellular carcinoma treatment. \u003cem\u003eImmunol. Lett.\u003c/em\u003e \u003cb\u003e275\u003c/b\u003e, 107003 (2025).\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eHuang, J. X. et al. A Study on Overcoming Post-TACE Drug Resistance in HCC Based on Controllable Oxygen Release-Magnetic Hyperthermia Therapy. \u003cem\u003eAdv. Healthc. Mater.\u003c/em\u003e \u003cb\u003ee2402253\u003c/b\u003e \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1002/adhm.202402253\u003c/span\u003e\u003cspan address=\"10.1002/adhm.202402253\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e (2024).\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eWang, Z., Li, Q. \u0026amp; Liang, B. Hypoxia as a Target for Combination with Transarterial Chemoembolization in Hepatocellular Carcinoma. \u003cem\u003ePharmaceuticals\u003c/em\u003e \u003cb\u003e17\u003c/b\u003e, 1057 (2024).\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"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":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"","lastPublishedDoi":"10.21203/rs.3.rs-6558171/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6558171/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eTransarterial chemoembolization (TACE) combined with PD-(L)1 inhibitors and molecular targeted therapies (MTT) has demonstrated significant improvements in progression-free survival (PFS), overall survival (OS).This retrospective study investigated TACE-PD-(L)1-MTT combination therapy's role in preventing TACE resistance in advanced HCC. Among 604 eligible patients (532 TACE alone vs. 72 combination) after propensity score matching, TACE resistance occurrence was evaluated post-3 treatment cycles. Combination therapy significantly reduced resistance incidence (9.7% vs. 38.8%, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) and demonstrated superior efficacy in inhibiting tumor progression compared to TACE monotherapy. These findings support the preventive potential of triple combination therapy against TACE resistance while improving clinical outcomes in advanced HCC .\u003c/p\u003e","manuscriptTitle":"TACE Combined with PD-L1 Inhibitors Effectively Mitigates TACE Resistance in Advanced Hepatocellular Carcinoma: A Propensity Score-Matched Study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-08-13 11:56:38","doi":"10.21203/rs.3.rs-6558171/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"db2bf3aa-f3d8-415f-b531-021ec360e184","owner":[],"postedDate":"August 13th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":52922962,"name":"Biological sciences/Cancer"},{"id":52922963,"name":"Health sciences/Medical research"},{"id":52922964,"name":"Health sciences/Oncology"}],"tags":[],"updatedAt":"2025-08-20T13:09:20+00:00","versionOfRecord":[],"versionCreatedAt":"2025-08-13 11:56:38","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-6558171","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6558171","identity":"rs-6558171","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}