Journal of Hepatocellular Carcinoma最新文献

{"title":"Validation of the Up7-ALBI Score for Prognostication in Unresectable Hepatocellular Carcinoma Treated with Atezolizumab Plus Bevacizumab.","authors":"Chien-Hung Lu, Wei-Yu Kao, Yao-Yu Hsieh, Chia-Chi Wang, Ming-Shun Wu, Chih-Horng Wu, Tsung-Hao Liu, Wei-Yi Ting, Shan-Chia Wu, Kai-I Chuang, Chien-Wei Su, Chun-Chao Chang, San-Chi Chen","doi":"10.2147/JHC.S638385","DOIUrl":"10.2147/JHC.S638385","url":null,"abstract":"<p><strong>Purpose: </strong>A well-established prognostic scoring system for unresectable hepatocellular carcinoma (uHCC) receiving systemic therapy is lacking. The Up7-ALBI score has shown prognostic value for lenvatinib. This study aimed to validate its prognostic value in uHCC treated with atezolizumab plus bevacizumab (atezo-bev).</p><p><strong>Patients and methods: </strong>This retrospective multicenter study included 225 patients with uHCC who received first-line atezo-bev in Taiwan between 2017 and 2025. The Up7-ALBI score (0-2), combining tumor burden (within vs beyond up-to-7) and ALBI grade (1 vs 2-3), categorized patients into low-, intermediate-, and high-risk groups. The score was used to stratify progression-free survival (PFS) and overall survival (OS), with multivariate Cox analysis performed. Prognostic performance was compared with previously reported scoring systems.</p><p><strong>Results: </strong>The objective response rate (ORR) and disease control rate were 44.4% and 60.4%, respectively, and the median PFS and OS were 7.0 and 23.8 months. Among the 225 enrolled patients, 178 patients had complete data for Up7-ALBI analysis. The Up7-ALBI score significantly stratified outcomes, with median OS not reached, 36.0 months, and 9.2 months for scores 0, 1, and 2 (p < 0.01); median PFS of 13.4, 7.9, and 5.8 months (p < 0.01); and ORR of 66.7%, 52.2%, and 32.9%, respectively (p < 0.01). Multivariate analysis showed that Up7-ALBI scores 1 and 2, along with macrovascular invasion, were independent risk factors for OS. The Up7-ALBI score demonstrated the lowest Akaike information criterion (484.3) among the previously proposed scores.</p><p><strong>Conclusion: </strong>This study validated the Up7-ALBI score for uHCC receiving atezo-bev. Its consistent prognostic performance across systemic therapies supports its potential as a simple, clinically applicable risk-stratification tool.</p>","PeriodicalId":15906,"journal":{"name":"Journal of Hepatocellular Carcinoma","volume":"13 ","pages":"638385"},"PeriodicalIF":3.9,"publicationDate":"2026-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13644561/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149137003","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Very Early Recurrence as a Dynamic Prognostic Stratifier After Curative Hepatectomy for Hepatocellular Carcinoma: A Landmark Analysis with Internal Validation and Machine-Learning Benchmarking.","authors":"Yun Cong, Ziwei Ma, Shitao Lei, Yaoqiang Bao, Xiyao Wei, Ruhai Huang, Tuerganaili Aji, Yingmei Shao","doi":"10.2147/JHC.S641664","DOIUrl":"10.2147/JHC.S641664","url":null,"abstract":"<p><strong>Background: </strong>Very early recurrence (VER, defined as recurrence within 12 months) after hepatocellular carcinoma (HCC) resection is often linked to poor survival, but conventional survival analyses stratified by recurrence status are inherently susceptible to guarantee-time bias. The relation between VER and post-recurrence survival also remains uncertain.</p><p><strong>Methods: </strong>This retrospective cohort included 526 patients with histopathologically confirmed HCC who underwent curative hepatectomy at the First Affiliated Hospital of Xinjiang Medical University between January 2016 and July 2025. A 12-month landmark cohort included patients alive beyond 12 months after surgery. Patients were split 7:3 into training and internally held-out validation cohorts. Landmark Cox models, a time-varying Cox model, post-recurrence survival analyses, and machine-learning benchmarking were performed. Missing primary-model values were median-imputed; multiple imputation was not used.</p><p><strong>Results: </strong>The landmark cohort included 486 patients; 82 had VER. The proportional-hazards assumption was violated for VER; the conventional adjusted Cox model estimated an average HR of 3.86 (95% CI, 2.81-5.29; P < 0.001) over post-landmark follow-up. The association varied over time, with model-estimated HRs of 10.06 at 1 month and 2.23 at 60 months after the landmark. In the internally held-out validation cohort, adding VER to the conventional Cox model improved the C-index from 0.591 (95% CI, 0.508-0.675) to 0.716 (95% CI, 0.633-0.797; C-index difference = 0.125, 95% CI, 0.051-0.203; P = 0.002). VER was not independently associated with post-recurrence mortality (HR, 1.23; 95% CI, 0.87-1.75; P = 0.25).</p><p><strong>Conclusions: </strong>Among patients alive at the 12-month landmark, VER was associated with higher subsequent mortality and improved discrimination in an internally held-out cohort. External validation is required before use for individual risk prediction or surveillance decisions.</p>","PeriodicalId":15906,"journal":{"name":"Journal of Hepatocellular Carcinoma","volume":"13 ","pages":"641664"},"PeriodicalIF":3.9,"publicationDate":"2026-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13641000/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149110603","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development and External Validation of a Multimodal Machine Learning Model Integrating Preoperative Contrast-Enhanced CT Radiomics and Clinicopathological Features for Predicting Early Extrahepatic Recurrence After Hepatectomy for Hepatocellular Carcinoma.","authors":"Yanze Li, Xiaolong Luo, Qilin Li, Yanwei Wang, Jiazhi Zhang, Yi Li, Bo Li, Kangyi Jiang, Xiaoli Yang","doi":"10.2147/JHC.S646171","DOIUrl":"10.2147/JHC.S646171","url":null,"abstract":"<p><strong>Background: </strong>Early extrahepatic recurrence (eEHR) after hepatectomy for hepatocellular carcinoma (HCC) significantly affects patient prognosis; however, an accurate predictive framework integrating radiomics with clinicopathological features is currently lacking. This study aims to develop and validate a multimodal machine learning model for prediction of early postoperative extrahepatic recurrence risk, thereby offering a basis for individualized postoperative intervention strategies.</p><p><strong>Methods: </strong>A total of 208 patients who received surgical resection and had a postoperative pathological diagnosis of HCC were retrospectively enrolled from two centers between 2018 and 2023. The cohort was divided into a training set and an internal validation set at a 7:3 ratio. An external validation set was also established. Preoperative enhanced CT radiomic features and clinicopathological characteristics were extracted. After screening for key features using regression analysis, multiple machine learning prediction models were constructed via nested k-fold cross validation. The performance of the models was evaluated, and survival analysis was subsequently conducted.</p><p><strong>Results: </strong>Among the 208 patients, 55 (26.4%) had postoperative eEHR. The most common site of recurrence was the lung (26 cases, 47.3%), followed by lymph nodes (12 cases, 21.8%) and bone (10 cases, 18.2%). Three core clinicopathological features and four key radiomic features were identified. A multimodal predictive model for HCC-eEHR was developed using the Random Forest algorithm. This model achieved an AUC of 0.852 (sensitivity 0.511, specificity 0.959) in the training cohort and an AUC of 0.836 (sensitivity 0.750, specificity 0.875, accuracy 0.850) in the external validation cohort. A 24-month landmark analysis (n=156) confirmed that patients developing eEHR within 24 months had significantly worse post-landmark overall survival (median 16.3 vs 47.7 months; HR=3.342, 95%CI: 1.570-7.112, P<0.001). Furthermore, the model demonstrated effective risk stratification in both cohorts (Southwest OS: HR=3.549, 95%CI: 2.097-6.006, P<0.001; Leshan OS: HR=3.839, 95%CI: 1.171-8.369, P=0.026).</p><p><strong>Conclusion: </strong>The developed multimodal prediction model may assist in assessing the risk of eEHR following HCC hepatectomy, thereby facilitating the timely identification of high-risk patients and informing personalized postoperative surveillance and treatment strategies.</p>","PeriodicalId":15906,"journal":{"name":"Journal of Hepatocellular Carcinoma","volume":"13 ","pages":"646171"},"PeriodicalIF":3.9,"publicationDate":"2026-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13641005/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149110537","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"HepaKineticNet: Deep Learning of CT-Derived Intratumoral Heterogeneity for Overall Survival Prediction in BCLC Stage B-C Hepatocellular Carcinoma Treated with Locoregional Therapy Plus First-Line TKI and Anti-PD-1 Therapy.","authors":"Jinpeng Li, Wenzhe Bu, Xiaotian Hanming, Qianqian Zhang, Jinlong Song, Wei Chen","doi":"10.2147/JHC.S636207","DOIUrl":"https://doi.org/10.2147/JHC.S636207","url":null,"abstract":"<p><strong>Purpose: </strong>To develop HepaKineticNet, a deep learning framework that models inter-phase kinetic dynamics on multi-phase contrast-enhanced CT (CECT) to generate intratumoral heterogeneity (ITH) maps, and to assess in an independent external cohort whether a clinical-radiomics fusion model improves overall survival (OS) prediction in BCLC stage B-C hepatocellular carcinoma (HCC) treated with locoregional therapy plus first-line TKI and anti-PD-1 agents.</p><p><strong>Patients and methods: </strong>In this bi-institutional retrospective study, HepaKineticNet was developed using 359 patients from one institution (231 training, 128 validation) and evaluated in an independent external test cohort of 95 patients from a second institution. HepaKineticNet integrates a Spatial Kinetic Differential Attention module into an nnU-Net backbone, separately encoding arterial wash-in and delayed wash-out kinetics, with multiscale coefficient-of-variation self-supervision. Ten radiomics features (hierarchical filtering) and three clinical variables selected by LASSO-penalised Cox regression (10-fold cross-validation) were used to build clinical, radiomics, and fusion Cox models.</p><p><strong>Results: </strong>A total of 277 deaths occurred, 128 of them in the development cohort. Baseline characteristics were balanced (all P>0.05). In the external test cohort, the fusion model achieved a C-index of 0.713, exceeding the clinical model (0.651; P=0.012). Time-dependent AUCs at 1, 2, and 3 years were 0.760 (95%CI 0.651-0.864), 0.838 (95%CI 0.736-0.930), and 0.909 (95%CI 0.686-1.000), whereas those of the clinical model were 0.676, 0.742, and 0.772. Kaplan-Meier analysis showed median OS of 9.5 vs 19.0 months for high- vs low-risk strata (HR 3.02, 95%CI 1.86-4.91; P<0.001). Discrimination was consistent across ten prespecified subgroups.</p><p><strong>Conclusion: </strong>HepaKineticNet-derived ITH maps encode kinetic and spatial information that modestly improves individualized OS prediction and risk stratification in this combination-therapy HCC population, and may provide a noninvasive decision-support adjunct pending prospective validation.</p>","PeriodicalId":15906,"journal":{"name":"Journal of Hepatocellular Carcinoma","volume":"13 ","pages":"636207"},"PeriodicalIF":3.9,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13637505/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149110580","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hispidulin Suppresses Hepatocellular Carcinoma Proliferation by Targeting PI3K-Akt Pathway: A Network Pharmacology and Experimental Validation Study.","authors":"Xulei Zhang, Yuan Yang, Zhiyuan Xu, Miaoyang Chen, Anyin Yang, Yongfeng Yang","doi":"10.2147/JHC.S613778","DOIUrl":"https://doi.org/10.2147/JHC.S613778","url":null,"abstract":"<p><strong>Purpose: </strong>As a natural compound present in a variety of plants, hispidulin has an inhibitory effect on tumors.</p><p><strong>Methods: </strong>In this study, we combined network pharmacology, bioinformatics methods and experimental verification to explore the potential targets of hispidulin in inhibiting hepatocellular carcinoma.</p><p><strong>Results: </strong>The network pharmacology analysis showed that the pharmacokinetic properties of hispidulin conformed to the Lipinski's five rules, and it had no hepatotoxicity, carcinogenicity, cytotoxicity, immunotoxicity, mutagenicity, and had the potential to be developed as a drug. The results of network pharmacology and bioinformatics analysis showed that hispidulin may interfere with the occurrence and progression of hepatocellular carcinoma by affecting CDK1, SRC, CCNB1, AURKB and PI3K/AKT signaling pathways. In vitro and in vivo studies, hispidulin inhibited the growth of hepatocellular carcinoma, induced apoptosis and inhibited migration of hepatocellular carcinoma cells and exhibited no significant toxicity to the normal tissues and organs of mice. It downregulated the expression of CDK1, CCNB1, SRC, AURKB protein and attenuated the PI3K/AKT pathway signal. These results suggest that hispidulin can exert anti-HCC effects through the PI3K/AKT pathway.</p><p><strong>Conclusion: </strong>Hispidulin can inhibit the occurrence and progression of hepatocellular carcinoma through multiple targets, showing good anti-tumor efficacy in vitro and in vivo, and has the potential to develop new therapeutic drugs for hepatocellular carcinoma.</p>","PeriodicalId":15906,"journal":{"name":"Journal of Hepatocellular Carcinoma","volume":"13 ","pages":"613778"},"PeriodicalIF":3.9,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13634230/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149110549","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transposable Element Dysregulation in Hepatocellular Carcinoma: Epigenetic Mechanisms, Immune Remodeling, and Translational Opportunities.","authors":"Xiaopeng Chen, Baoding Li, Hao Chai, Chengwei Yang, Rui Bai, Wenxiao Ma, Minghao Li","doi":"10.2147/JHC.S637546","DOIUrl":"https://doi.org/10.2147/JHC.S637546","url":null,"abstract":"<p><p>Hepatocellular carcinoma (HCC) commonly develops in the context of chronic liver injury, viral hepatitis, metabolic dysfunction, alcohol-related liver disease and cirrhosis. Although immune checkpoint inhibitor-based combination therapies have improved the treatment of unresectable HCC, primary and acquired resistance and the lack of reliable predictive biomarkers continue to limit precision treatment. Transposable elements (TEs) and TE-derived sequences represent a regulatory layer linking epigenetic disruption, aberrant transcription and immune remodelling. In HCC, DNA hypomethylation, altered repressive histone modifications, dysfunction of TE-silencing machinery and dysregulated RNA-level control may promote the reactivation of LINE-1, HERV/ERV and other TE-derived sequences. Reactivated TEs may influence tumour-cell states and the immune microenvironment through cryptic promoter or enhancer activity, TE-derived transcripts, viral mimicry, innate immune sensing and potential tumour-associated antigens. HCC-specific evidence includes clinical associations of LINE-1 hypomethylation and mechanistic findings involving the TE/KDM1A/HNF4A axis and SETDB1-mediated HERV/ERV silencing and viral mimicry. Using a structured narrative literature search that emphasised studies published during the past five years while retaining relevant landmark studies, this review integrates the epigenetic, transcriptional, immune and translational dimensions of TE dysregulation in HCC. A five-level evidence framework is applied to distinguish HCC-specific mechanistic and in vivo evidence, HCC functional and cell-based findings, HCC clinical and omics associations, pan-cancer or non-HCC evidence, and hypothesis-generating candidates. This framework highlights the uneven maturity of the field and the need for locus-specific functional studies and independent clinical validation. TIGD family members are discussed as a hypothesis-generating example of TE-derived protein-coding candidates rather than as established HCC regulators, biomarkers or therapeutic targets.</p>","PeriodicalId":15906,"journal":{"name":"Journal of Hepatocellular Carcinoma","volume":"13 ","pages":"637546"},"PeriodicalIF":3.9,"publicationDate":"2026-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13633678/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149110575","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"DEB-TACE Combined with Immunotherapy and Targeted Therapy for Advanced Hepatocellular Carcinoma with Scapular Metastasis: A Case Report.","authors":"Wenxia Zhang, Dongxu Kang, Qiang Xu, Longzhen Piao","doi":"10.2147/JHC.S623085","DOIUrl":"https://doi.org/10.2147/JHC.S623085","url":null,"abstract":"<p><strong>Background: </strong>Advanced hepatocellular carcinoma (HCC) with massive intrahepatic tumors and bone metastases is associated with poor prognosis, and standard treatment options are limited. Bone metastases, particularly to rare sites such as the scapula, pose additional therapeutic challenges.</p><p><strong>Case presentation: </strong>We report a patient with a giant intrahepatic HCC and scapular metastasis. The patient received three sessions of drug-eluting bead transarterial chemoembolization (DEB-TACE) combined with systemic therapy using lenvatinib and camrelizumab. Marked radiological regression and improvement in tumor markers were observed. The patient remained progression-free at the last documented follow-up of 16 months.</p><p><strong>Conclusion: </strong>The combination of DEB-TACE, lenvatinib, and camrelizumab for treating advanced hepatocellular carcinoma with scapular metastasis was shown to be feasible in this case and was associated with sustained disease control of both intrahepatic and extrahepatic lesions.</p>","PeriodicalId":15906,"journal":{"name":"Journal of Hepatocellular Carcinoma","volume":"13 ","pages":"623085"},"PeriodicalIF":3.9,"publicationDate":"2026-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13625843/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149110524","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pan-Cancer Landscape of the Novel Oxygen Sensor ADO and Its Potential Role in Hepatocellular Carcinoma.","authors":"Jie Huang, Ying Xu, Yuqing Wang, Yuzhou Nie, Yidan Chen, Juan Shen, Shenglin Ma, Xueqin Chen","doi":"10.2147/JHC.S637010","DOIUrl":"10.2147/JHC.S637010","url":null,"abstract":"<p><strong>Background: </strong>Hypoxia is a key driver of tumor progression across cancers, yet oxygen-sensing mechanisms beyond HIFs remain underexplored. 2-Aminoethanethiol dioxygenase (ADO) has recently been identified as an oxygen sensor, but its role in malignancy is poorly defined. We conducted a pan-cancer analysis of ADO with a special focus on hepatocellular carcinoma (HCC), to assess its oncogenic significance and clinical potential.</p><p><strong>Methods: </strong>A multi-omics pan-cancer analysis of ADO expression and survival was performed using TCGA and GTEx, with validation in HCC across ICGC, GEO, and CNHPP proteomic cohorts. Correlations with genetic, epigenetic, immune, and pathways were evaluated. Drug sensitivity was predicted. Functional validation was conducted in HCC cells through proliferation, colony formation, Western blotting, and xenograft assays.</p><p><strong>Results: </strong>ADO was aberrantly expressed across cancers and showed cancer type-specific survival associations. Integrative analyses revealed links with tumor mutation burden, microsatellite instability, chromatin regulator methylation, RNA modification, proliferative signaling (G2M checkpoint, MYC, TGF-β), an immunosuppressive microenvironment, and negative correlations with ROS-responsive genes. In HCC, ADO was consistently overexpressed, associated with advanced stage, poor differentiation, residual disease, and unfavorable survival across independent cohorts. ADO-high HCC showed reduced predicted responsiveness to checkpoint blockade but increased sensitivity to sorafenib and fluorouracil. Experimentally, ADO overexpression activated ERK signaling, upregulated CD276 and HMGB1, and promoted HCC cell proliferation, while ADO depletion suppressed tumor growth in vitro and in vivo, reversible upon re-expression.</p><p><strong>Conclusion: </strong>ADO plays oncogenic and immunomodulatory roles in HCC, and may serve as a potential prognostic biomarker and therapeutic target in liver cancer.</p>","PeriodicalId":15906,"journal":{"name":"Journal of Hepatocellular Carcinoma","volume":"13 ","pages":"637010"},"PeriodicalIF":3.9,"publicationDate":"2026-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13620309/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149080449","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Associations of Type 2 Diabetes with Tumor Budding and Microvascular Invasion in Resected Hepatocellular Carcinoma.","authors":"Zhuoren Tang, Fei Jia, Shuo Xing, Jia Gao, Hangyu Ren, Zerong Yang, Kunjin Wu, Fei Xue, Xing Zhang, Kaibo Yang, Kai Qu","doi":"10.2147/JHC.S640109","DOIUrl":"10.2147/JHC.S640109","url":null,"abstract":"<p><strong>Purpose: </strong>Type 2 diabetes mellitus (DM) may influence invasive tumor phenotypes in hepatocellular carcinoma (HCC). We evaluated associations of pre-existing DM with tumor budding (TB), microvascular invasion (MVI), and postoperative outcomes.</p><p><strong>Patients and methods: </strong>This single-center retrospective cohort included 924 patients with pathologically confirmed HCC who underwent curative-intent hepatectomy from 2015 to 2020. Two blinded pathologists assessed TB and MVI. Logistic regression evaluated pathological associations, and Kaplan-Meier and Cox models evaluated recurrence-free survival (RFS) and overall survival (OS). Glycemic and treatment analyses in patients with DM were exploratory and used variable-specific available cases.</p><p><strong>Results: </strong>Among 924 patients, 124 (13.4%) had DM, 314 (34.0%) were TB-positive, and 493 (53.4%) were MVI-positive. DM was associated with TB-positive status (adjusted odds ratio [OR], 3.508; 95% confidence interval [CI], 2.287-5.381; <i>P</i> < 0.001) and MVI-positive status (adjusted OR, 3.364; 95% CI, 2.083-5.434; <i>P</i> < 0.001). In the primary overlap-weighted PS analysis, DM was not associated with RFS (hazard ratio [HR], 1.453; 95% CI, 0.778-2.714; <i>P</i> = 0.240) or OS (HR, 1.127; 95% CI, 0.556-2.284; <i>P</i> = 0.740). TB remained associated with RFS but not OS in expanded Cox models, whereas MVI was associated with both outcomes.</p><p><strong>Conclusion: </strong>Pre-existing DM was associated with TB-positive and MVI-positive status after hepatectomy for HCC. The primary PS analysis did not provide evidence of an independent DM survival association. Glycemic-control and treatment findings were exploratory and require prospective external validation.</p>","PeriodicalId":15906,"journal":{"name":"Journal of Hepatocellular Carcinoma","volume":"13 ","pages":"640109"},"PeriodicalIF":3.9,"publicationDate":"2026-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13616152/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149069517","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy of Lenvatinib versus Bevacizumab in Triple Therapy with Immune Checkpoint Inhibitors and Interventional Therapy for Hepatocellular Carcinoma with Macrovascular Invasion: A Multi-Center Real-World Retrospective Study.","authors":"Jiazhi Zhang, Yongfa Liu, Yi Ding, Zhouyi Deng, Bo Jiang, Benjian Gao, Shuai Hu, Jianming Sun, Xiaoli Yang, Hui Zhang, Bo Li","doi":"10.2147/JHC.S640366","DOIUrl":"10.2147/JHC.S640366","url":null,"abstract":"<p><strong>Background: </strong>Hepatocellular carcinoma (HCC) patients with macrovascular invasion (MaVI) continue to experience a dismal prognosis and the optimal drug combination choices remain undefined. The aim of this study was to compare the clinical efficacy and safety of lenvatinib-based triple therapy versus bevacizumab-based triple therapy, as first-line treatment for patients with MaVI.</p><p><strong>Patients and methods: </strong>This retrospective multicenter study enrolled 184 consecutive patients from three centers in China, all of whom received first-line lenvatinib (n=126) or bevacizumab (n=58) combined with immune checkpoint inhibitors (ICIs) and interventional therapy (TACE and/or HAIC). The primary endpoints were progression-free survival (PFS) and overall survival (OS). Propensity score matching (PSM) was applied to balance baseline clinical characteristics, and inverse probability of treatment weighting (IPTW) was subsequently applied to assess the robustness of the findings.</p><p><strong>Results: </strong>In the overall cohort, median PFS did not differ significantly between the lenvatinib group and the bevacizumab group (hazard ratio [HR]: 0.694; 95% confidence interval [CI]: 0.477-1.008; P = 0.053). However, the PFS difference reached statistical significance after PSM (8.40 months in the lenvatinib group vs 13.00 months in the bevacizumab group; HR: 0.601; 95% CI: 0.389-0.928; P = 0.02) and after IPTW (HR: 0.609; 95% CI: 0.415-0.894; P = 0.011). No significant difference in OS was observed between the two groups in the unadjusted cohort (HR: 0.809; 95% CI: 0.512-1.279; P = 0.362), after PSM (20.23 vs 35.20 months; HR: 0.634; 95% CI: 0.376-1.069; P = 0.085), or after IPTW (HR: 0.686; 95% CI: 0.432-1.089; P = 0.11). Multivariate analysis in the matched cohort showed that bevacizumab-based triple therapy was associated with prolonged PFS compared with lenvatinib-based triple therapy. There was no significant difference between the two groups in the incidence of grade 3-4 adverse events (58.57% vs 66.00%, P = 0.409) and grade 3-4 gastrointestinal hemorrhage (12.86% vs 8.00%, P = 0.399).</p><p><strong>Conclusion: </strong>In HCC patients with MaVI, bevacizumab-based triple therapy was associated with prolonged PFS compared to lenvatinib-based triple therapy, with no significant difference in OS.</p>","PeriodicalId":15906,"journal":{"name":"Journal of Hepatocellular Carcinoma","volume":"13 ","pages":"640366"},"PeriodicalIF":3.9,"publicationDate":"2026-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13615806/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149061357","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}