Journal of Hepatocellular Carcinoma最新文献

{"title":"Stage-Dependent Efficacy of TACE Combined with Tyrosine Kinase and Immune Checkpoint Inhibitors as Conversion Therapy for Unresectable Hepatocellular Carcinoma: A Multicenter Retrospective Study.","authors":"Haozhe Zhou, Lin Ye, Wanrong Yue, Kangqiang Lin, Bixia Chi, Jiaye Liao, Xuanting Chen, Hao Shi, Tao Wang, Zhao Jiang, Jiguang Luo, Borong Huang, Yaqun Yu, Qingzhi He","doi":"10.2147/JHC.S619735","DOIUrl":"10.2147/JHC.S619735","url":null,"abstract":"<p><strong>Purpose: </strong>This study was designed to compare the efficacy and safety of transarterial chemoembolization (TACE) alone versus TACE combined with tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs) as conversion therapy for patients with initially unresectable hepatocellular carcinoma (HCC), and to identify which patient populations benefit most from triple combination therapy.</p><p><strong>Methods: </strong>This multicenter retrospective study included 260 patients with initially unresectable HCC treated at 7 centers in China between January 2020 and January 2025. Of these, 150 received triple conversion therapy (TACE + TKI + ICI) and 110 received TACE alone. Inverse probability of treatment weighting (IPTW) was applied to minimize confounding. Overall survival (OS), progression-free survival (PFS), tumor response, conversion hepatectomy rates, and treatment-related adverse events (TRAEs) were compared between the two groups.</p><p><strong>Results: </strong>After IPTW, all standardized mean differences were < 0.10. Triple therapy was associated with significantly longer median OS (31.0 vs 16.5 months; HR 0.51, 95% CI: 0.39-0.68, P < 0.001) and PFS (10.2 vs 5.8 months; HR 0.55, 95% CI: 0.43-0.72, P < 0.001), with benefit maintained after IPTW adjustment. The modified RECIST objective response rate (59.3% vs 29.1%) and conversion hepatectomy rate (34.7% vs 12.7%) were both higher with triple therapy (both P < 0.001). The OS benefit was significant in BCLC stage B (HR 0.37, P < 0.001) and stage C (HR 0.47, P < 0.001) but not stage A (HR 0.78, P = 0.480). Grade 3-4 TRAEs did not differ significantly (30.0% vs 24.5%, P = 0.406).</p><p><strong>Conclusion: </strong>Triple conversion therapy was well tolerated and provided superior efficacy over TACE alone in patients with intermediate- or advanced-stage unresectable HCC. No significant survival difference was detected in early-stage (BCLC stage A) disease, supporting a stage-stratified approach to conversion therapy selection.</p>","PeriodicalId":15906,"journal":{"name":"Journal of Hepatocellular Carcinoma","volume":"13 ","pages":"619735"},"PeriodicalIF":3.9,"publicationDate":"2026-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13387194/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148549332","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":"Adjuvant Sintilimab Plus Bevacizumab After Curative Resection of Spontaneously Ruptured Hepatocellular Carcinoma: Protocol for a Prospective, Exploratory, Single-Arm Study (CLEAR-2).","authors":"Yuan Cheng, Feng Ye, Hui-Chuan Sun, Yongjun Chen","doi":"10.2147/JHC.S614872","DOIUrl":"10.2147/JHC.S614872","url":null,"abstract":"<p><strong>Background: </strong>Spontaneous rupture of hepatocellular carcinoma (srHCC) is a life-threatening complication associated with high perioperative mortality and increased postoperative recurrence, particularly peritoneal dissemination. Although timely haemostasis and curative-intent resection allow selected patients to achieve meaningful survival, postoperative management remains poorly defined, and patients with srHCC are usually excluded from major adjuvant trials.</p><p><strong>Methods: </strong>CLEAR-2 is a prospective, exploratory, multicentre, single-arm study evaluating adjuvant sintilimab plus bevacizumab biosimilar after R0 resection of srHCC. Thirty-five patients with imaging- or intraoperatively confirmed spontaneous rupture, China Liver Cancer (CNLC) stage I-II disease, complete radiological response 4-8 weeks after surgery, ECOG performance status 0-1, Child-Pugh class A liver function, and adequate organ function will be enrolled. Preoperative transarterial embolisation for haemostasis is permitted as a single bridging procedure without chemotherapeutic agents, followed by surgery within 2 weeks. Treatment consists of sintilimab 200 mg plus bevacizumab biosimilar 15 mg/kg intravenously every 3 weeks for up to 1 year or until recurrence, unacceptable toxicity, or withdrawal. The primary endpoint is disease-free survival. Secondary endpoints include overall survival, safety, and recurrence patterns. Tumour assessments will be performed every 12 weeks using contrast-enhanced CT or MRI according to RECIST version 1.1.</p><p><strong>Conclusion: </strong>CLEAR-2 is designed to generate preliminary prospective evidence on the feasibility, safety, and antitumour activity of adjuvant sintilimab plus bevacizumab in a highly selected, high-risk srHCC population. The findings may inform future randomized or comparative studies of postoperative strategies for srHCC.</p><p><strong>Trial registration: </strong>NCT07331883.</p>","PeriodicalId":15906,"journal":{"name":"Journal of Hepatocellular Carcinoma","volume":"13 ","pages":"614872"},"PeriodicalIF":3.9,"publicationDate":"2026-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13383990/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148604112","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":"Prognostic Relevance of Neddylation-Related Genes in Hepatocellular Carcinoma.","authors":"Qiyue Sun, Guang Tan","doi":"10.2147/JHC.S610030","DOIUrl":"10.2147/JHC.S610030","url":null,"abstract":"<p><strong>Purpose: </strong>Targeting neddylation offers a potential therapeutic strategy for hepatocellular carcinoma (HCC). This retrospective study aims to identify genes linked to HCC prognosis associated with neddylation through bioinformatics.</p><p><strong>Patients and methods: </strong>The research used publicly available datasets. Neddylation-related genes and survival-associated differentially expressed genes (DEGs) were intersected to identify key genes, which underwent enrichment analysis. Least absolute selection and shrinkage operator (LASSO)-Cox and multivariate Cox regression analyses were performed to identify prognostic genes and build a risk model. Potential mechanisms were explored via immune microenvironment and single-cell analysis. Finally, prognostic gene expression was validated in clinical tumor samples using real-time quantitative PCR (RT-qPCR).</p><p><strong>Results: </strong>Through methodical investigation, 62 intersection genes were found, mainly enriched in \"DNA duplex unwinding\" and \"p53 signaling pathway\". Six prognostic genes were further determined (SOCS2, DIRAS2, LPL, KRT17, BFSP1, and POF1B). RT-qPCR results confirmed the downregulation of SOCS2 and the upregulation of DIRAS2, LPL, KRT17, BFSP1, and POF1B in HCC. Risk prediction model based on these genes exhibited high predictive accuracy. Subsequently, analysis of the immunological microenvironment showed that the infiltration levels of 8 immune cell types varied significantly among risk categories. M0 macrophages had the highest negative correlation with SOCS2 and the strongest positive association with DIRAS2. Single-cell analysis showed that SOCS2 had higher expression levels in endothelial cells and significant differential expression in most cellular classifications.</p><p><strong>Conclusion: </strong>Six prognosis-associated genes (SOCS2, DIRAS2, LPL, KRT17, BFSP1, and POF1B) as predictive biomarkers for HCC were identified, and a high-accuracy risk model was developed, providing predictive and prognostic references for HCC risk stratification and clinical management.</p>","PeriodicalId":15906,"journal":{"name":"Journal of Hepatocellular Carcinoma","volume":"13 ","pages":"610030"},"PeriodicalIF":3.9,"publicationDate":"2026-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13371868/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148455985","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":"Tumor Burden Thresholds Associated with Successful Downstaging After Yttrium-90 Radioembolization in Hepatocellular Carcinoma Beyond UCSF Criteria.","authors":"Chun-Hua Chiu, Chun-Yen Yu, Hsin-You Ou, Leung-Chit Tsang, Po-Hsun Huang, Ching-Chun Weng, Yi Lu, Chao-Long Chen, Yu-Fan Cheng","doi":"10.2147/JHC.S613375","DOIUrl":"10.2147/JHC.S613375","url":null,"abstract":"<p><strong>Purpose: </strong>Hepatocellular carcinoma (HCC) is frequently diagnosed at advanced stages, limiting access to curative therapies. Yttrium-90 (Y-90) trans-arterial radioembolization (TARE) has been used for tumor downstaging to enable surgical resection or liver transplantation; however, the factors associated with successful downstaging and potential selection thresholds remain unclear.</p><p><strong>Patients and methods: </strong>We retrospectively analyzed 65 patients with unresectable HCC exceeding the University of California, San Francisco (UCSF) criteria who underwent Y-90 TARE between 2020 and 2024. Tumor burden parameters, dosimetric features, treatment response, overall survival (OS), and progression-free survival (PFS) were evaluated. Receiver operating characteristic (ROC) analysis was performed to identify exploratory thresholds associated with successful downstaging, and survival outcomes were assessed using Kaplan-Meier methods.</p><p><strong>Results: </strong>Down-staging to within UCSF criteria was achieved in 58.5% of patients. Successfully down-staged patients had significantly longer OS than non-downstaged patients (median OS, not reached vs. 18.8 months; p = 0.034). ROC analysis identified exploratory tumor burden thresholds associated with downstaging failure, including largest tumor diameter ≥7.8 cm, tumor volume ≥265 cm³, and a composite tumor number-diameter score >11. The presence of multiple adverse tumor burden factors was associated with a high likelihood of downstaging failure. When adequate tumor radiation delivery was achieved, a tumor-to-normal uptake ratio (T/N) >4 predicted successful downstaging in tumors <7.8 cm, whereas its prognostic value diminished in larger lesions.</p><p><strong>Conclusion: </strong>Y-90 TARE enables effective downstaging in a substantial proportion of patients with advanced HCC and may facilitate subsequent curative surgery or living donor liver transplantation. Tumor burden metrics and size-dependent T/N ratios were associated with successful downstaging and may assist patient selection for Y-90 TARE. These findings should be considered exploratory and warrant validation in larger prospective studies.</p>","PeriodicalId":15906,"journal":{"name":"Journal of Hepatocellular Carcinoma","volume":"13 ","pages":"613375"},"PeriodicalIF":3.9,"publicationDate":"2026-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13367484/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148447519","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":"<i>SNHG6</i> Promotes Lipid Metabolic Reprogramming in Hepatocellular Carcinoma via Upregulation of SCD.","authors":"Xin Zheng, Jiajun Lu, Huiping Qiu, Qianya Jin, Lulu Cao, Jie Liu, Pengxia Song, Shuihong Yao","doi":"10.2147/JHC.S610313","DOIUrl":"10.2147/JHC.S610313","url":null,"abstract":"<p><strong>Objective: </strong>The aim of this study was to examine the role and molecular mechanism of the long non-coding RNA small nucleolar RNA host gene 6 (<i>SNHG6</i>) in lipid metabolic reprogramming in hepatocellular carcinoma (HCC).</p><p><strong>Methods: </strong>The effects of <i>SNHG6</i> knockdown on the proliferative and metastatic capacities of Huh7 and LM3 cells were assessed using CCK-8 assays, colony formation assays, and Transwell migration and invasion assays. Lipid alterations were assessed using LipidTOX staining, triglyceride (TG) quantification, and non-targeted metabolomics. Downstream genes and signaling pathways were analyzed by RNA sequencing, quantitative reverse transcription polymerase chain reaction, and Western blotting. Rescue experiments were conducted by overexpressing stearoyl-coenzyme A desaturase (SCD) in <i>SNHG6</i>-knockdown cells. The regulation of SCD expression by <i>SNHG6</i> via the AMPK/ sterol regulatory element-binding protein-1 (SREBP1) axis was examined by Western blotting. Additional rescue experiments were conducted using AMPK inhibitors and overexpression of SREBP1 in <i>SNHG6</i>-knockdown cells.</p><p><strong>Results: </strong><i>SNHG6</i> expression was significantly upregulated in tumor tissues from patients with HCC and was associated with poor prognosis. <i>SNHG6</i> silencing reduced lipid droplet accumulation and TG content in HCC cells and suppressed cellular proliferation, migration, and invasion. Further analyses demonstrated that <i>SNHG6</i> knockdown decreased SCD expression, whereas overexpression of SCD restored lipogenesis and reversed the suppression of proliferation and metastatic capacity induced by <i>SNHG6</i> silencing. Mechanistically, the data suggested that <i>SNHG6</i> upregulated SREBP1 expression through the AMPK signaling pathway, thereby enhancing SCD expression and promoting lipid metabolism. The reduction in lipogenesis and inhibition of proliferation and metastatic capacity induced by <i>SNHG6</i> silencing were reversed by AMPK pathway inhibition and SREBP1 overexpression.</p><p><strong>Conclusion: </strong>Taken together, these findings suggested that SNHG6 may regulate lipid metabolism in HCC by linking to SCD-centered lipogenic regulation via the AMPK/SREBP1 pathway, pointing to a potential SNHG6/AMPK/SREBP1/SCD signaling axis.</p>","PeriodicalId":15906,"journal":{"name":"Journal of Hepatocellular Carcinoma","volume":"13 ","pages":"610313"},"PeriodicalIF":3.9,"publicationDate":"2026-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13367348/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148447472","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":"Correlation of Insulin and/or Insulin Secretagogues with the Risk of Hepatocellular Carcinoma and All-Cause Mortality Among Patients with Chronic Hepatitis B and Type 2 Diabetes Mellitus: A Retrospective Cohort Study.","authors":"Ming Zhou, Peng Zhou, Wenchao Xu, Dongmei Zhu, Fan Zhang, Wenjian Li, Chunyan Ye","doi":"10.2147/JHC.S611091","DOIUrl":"10.2147/JHC.S611091","url":null,"abstract":"<p><strong>Background: </strong>Patients with chronic hepatitis B (CHB) have a higher risk of developing hepatocellular carcinoma (HCC), causing poor prognosis. Type 2 diabetes mellitus (T2DM), a common comorbidity of CHB, further elevates HCC risk. Insulin and insulin secretagogues are commonly used antidiabetic medications (ADMs) that lower blood glucose by elevating circulating insulin levels. This study aimed to explore the association of insulin and/or insulin secretagogues with the risk of HCC and all-cause mortality among patients with CHB and T2DM.</p><p><strong>Patients and methods: </strong>This study included 696 patients diagnosed with CHB and T2DM between January 2016 and December 2019, who were divided into four groups. Group 1 received insulin and/or insulin secretagogues; Group 2 received no ADMs; Group 3 received other ADMs except for insulin and insulin secretagogues; Group 4 received insulin and/or insulin secretagogues in combination with other ADMs. Cox proportional hazards regression models were constructed to assess the risk of developing HCC and death. Subgroup analysis and sensitivity analysis were conducted to assess the robustness of the findings.</p><p><strong>Results: </strong>Throughout the follow-up period (median 77.5 months for HCC, 80 months for all-cause mortality), Group 1 had a significantly higher incidence of both HCC and all-cause mortality compared with other groups (both P < 0.001). After adjusting for potential covariates, compared with Group 2, Group 1 was associated with a higher risk of developing HCC (HR = 4.42, 95% CI: 1.75-11.17, P = 0.002) and all-cause mortality (HR = 2.46, 95% CI: 1.35-4.50, P = 0.003). Subgroup and sensitivity analyses confirmed robustness.</p><p><strong>Conclusion: </strong>This study found that the use of insulin and/or insulin secretagogues was associated with a higher incidence of HCC and all-cause mortality among patients with CHB and T2DM. However, when combining insulin and/or insulin secretagogues with other types of ADMs, no increased risk was observed.</p>","PeriodicalId":15906,"journal":{"name":"Journal of Hepatocellular Carcinoma","volume":"13 ","pages":"611091"},"PeriodicalIF":3.9,"publicationDate":"2026-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13360819/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148437018","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 and Safety of Modified Sishen Decoction for Tyrosine Kinase Inhibitor-Induced Diarrhea in Hepatocellular Carcinoma: A Randomized Controlled Trial.","authors":"Jingwen Cao, Shengli He, Song Yu, Jie Shen, Nanhua Hu, Dan Yu, Tieliu Cao, Liwen Jiang, Junwei Peng, Xiaofeng Zhai","doi":"10.2147/JHC.S608479","DOIUrl":"10.2147/JHC.S608479","url":null,"abstract":"<p><strong>Background: </strong>Diarrhea is a common and dose-limiting toxicity of tyrosine kinase inhibitors (TKIs) in patients with hepatocellular carcinoma (HCC), for which current treatments are often insufficient. This study aimed to evaluate the efficacy and safety of Modified Sishen Decoction (MSD), a Traditional Chinese Medicine formula, for TKI-induced diarrhea.</p><p><strong>Methods: </strong>We conducted a single-blind, randomized controlled trial involving 60 HCC patients with TKI-induced diarrhea. Patients were randomly assigned (1:1) to receive either MSD capsules or montmorillonite powder capsules for 7 days. The primary outcome was the change in diarrhea grade (NCI CTCAE v4.0) from baseline to day 8. Secondary outcomes included changes in TCM-related symptom scores and safety.</p><p><strong>Results: </strong>At day 8, the MSD group demonstrated a significantly greater reduction in diarrhea grade compared to the montmorillonite group (OR=4.75, 95% CI: 1.50-15.05, P=0.008). The overall effective rate for diarrhea control was significantly higher in the MSD group (90% vs. 20%; P<0.001). Patients receiving MSD also reported greater improvement in systemic symptoms, including fatigue and poor appetite (total symptom score reduction, P<0.001). Adverse event rates were comparable between the two groups.</p><p><strong>Conclusion: </strong>In this trial, Modified Sishen Decoction was more effective than montmorillonite powder in reducing the severity of TKI-induced diarrhea and alleviating associated systemic symptoms in HCC patients, with a comparable safety profile. MSD may be a valuable therapeutic option for this challenging clinical problem.</p><p><strong>Clinical trial number: </strong>ChiCTR1900023194.</p>","PeriodicalId":15906,"journal":{"name":"Journal of Hepatocellular Carcinoma","volume":"13 ","pages":"608479"},"PeriodicalIF":3.9,"publicationDate":"2026-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13361394/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148437096","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":"SPP1+ Macrophages Promote Immunosuppression in Post-TACE Hepatocellular Carcinoma Involving Lactate-Induced Lactylation and Potential SPP1-CD44 Signaling.","authors":"Hongyu Wang, Guojun Liang, Ting Liu, Min He, Yang Jiang, Jinwei Li, Yushu Ouyang, Shufang Hao, Wendao Liu, Jiaping Li","doi":"10.2147/JHC.S603485","DOIUrl":"10.2147/JHC.S603485","url":null,"abstract":"<p><strong>Background: </strong>Transarterial chemoembolization (TACE) treats inoperable liver cancer by inducing tumor ischemia, but subsequent hypoxia can promote an immunosuppressive microenvironment. This study explores how TACE-related hypoxia influences immune cells through lactate metabolism and lactylation.</p><p><strong>Methods: </strong>Single-cell RNA sequencing of TACE-treated and newly diagnosed liver cancer samples was performed. Scores were assigned to lactate-related gene sets, and differentially expressed genes were identified. Bioinformatics analysis integrated scRNA-seq, TCGA, and GEO data. Machine learning derived a consensus gene signature, and a prognostic nomogram was constructed. The study evaluated immune infiltration and drug sensitivity. Key findings were validated via spatial transcriptomics, in vitro experiments, and immunofluorescence.</p><p><strong>Results: </strong>We identified seven distinct single-cell types, noting an increase in macrophage infiltration and a decrease in CD8+ T cells within the TACE group. A six-gene consensus signature related to lactate-comprising SPP1, DNASE1L3, HRG, TPX2, LAPTM4B, and G6PD-was identified and found to be significantly associated with poor prognosis. This consensus gene score and T, N staging constructed a prognostic nomogram validated by calibration curves and decision curves. We also found that SPP1+ macrophages were elevated in the TACE treatment group, with increased lactate-related gene set scores, and were associated with hypoxia, glycolysis, and inflammatory pathways. Cell communication analysis suggested a potential regulatory link between SPP1+ macrophages and CD8+ T cells, highlighting the potential involvement of the SPP1-CD44 axis. Cell experiments showed that hypoxic, lactate-rich environments lead to macrophage lactylation, increasing SPP1+ macrophages and decreasing CD8+ IFN-γ+ T cells. Spatial transcriptomics and immunofluorescence staining revealed co-localization of SPP1+ macrophages with CD8+ T cells.</p><p><strong>Conclusion: </strong>We established a lactate-associated six-gene signature and prognostic nomogram. The immunosuppressive microenvironment following TACE in liver cancer is highly correlated with the activation of lactate-related genes and an increase in SPP1+ macrophages. These macrophages are closely associated with CD8+ T cells dysfunction, with the SPP1-CD44 pathway serving as a candidate narrative for this intercellular crosstalk. These findings suggest that targeting lactate-induced lactylation or the potential SPP1-CD44 interaction may offer promising therapeutic opportunities to counteract immune evasion after TACE therapy.</p>","PeriodicalId":15906,"journal":{"name":"Journal of Hepatocellular Carcinoma","volume":"13 ","pages":"603485"},"PeriodicalIF":3.9,"publicationDate":"2026-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13356865/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148430551","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":"Etiology-Driven Mouse Models of Hepatocellular Carcinoma: Paving the Way for Precision Oncology.","authors":"Wuqing Cao, Yiping Fan, Heyi Chen, Jichun Sun, Xiaoxin Jin","doi":"10.2147/JHC.S621043","DOIUrl":"10.2147/JHC.S621043","url":null,"abstract":"<p><strong>Background: </strong>Hepatocellular carcinoma (HCC) is biologically heterogeneous, and its genomic alterations, inflammatory context, and tumor immune microenvironment are strongly shaped by the underlying etiology, including chronic hepatitis B virus (HBV) infection, metabolic dysfunction-associated steatotic liver disease (MASLD), and alcohol exposure. This etiological diversity complicates the selection and interpretation of preclinical models. Genetically engineered mouse models (GEMMs), particularly when combined with dietary, chemical, viral, or alcohol-related insults, provide useful systems for dissecting how defined genetic drivers interact with disease-specific liver environments in an immunocompetent host.</p><p><strong>Main body: </strong>This review summarizes etiology-aligned GEMMs and related mouse models for HCC. In HBV-related models, we discuss how viral antigen exposure, HBV-associated genomic instability, <i>Tert</i> activation, and <i>Trp53</i> loss support a multi-driver framework rather than a single-lesion model of carcinogenesis. In MASLD-associated HCC, we examine models involving Wnt/β-catenin activation, Acvr2a loss, <i>Pten</i> deficiency, and <i>MUP-uPA</i> driven steatohepatitis, emphasizing their value for studying immune exclusion, lactate-rich immunosuppression, IgA+ plasma-cell accumulation, and altered responses to immune checkpoint blockade. In alcohol-associated HCC, we review models centered on Aldh2 deficiency, ER stress-lysosomal lipid remodeling through the ATF4/LPLA2 axis, NF-κB-related inflammatory regulation, and neutrophil-driven tumor promotion. Across these etiologies, we compare model strengths and limitations, including tumor latency, penetrance, reproducibility, lack of cirrhotic remodeling, sex-dependent variability, microbiome-related environmental effects, and incomplete modeling of tumor-stroma co-evolution.</p><p><strong>Short conclusion: </strong>Etiology-aligned GEMMs can help match biological questions to appropriate preclinical platforms and generate testable hypotheses about therapy response. However, etiology alone should not be treated as a substitute for molecular profiling or clinical validation. Future models should integrate precise genetic engineering with fibrotic or cirrhotic backgrounds, microbiome-aware environmental modulation, and complementary human-relevant systems to better capture the complex evolution of human HCC.</p>","PeriodicalId":15906,"journal":{"name":"Journal of Hepatocellular Carcinoma","volume":"13 ","pages":"621043"},"PeriodicalIF":3.9,"publicationDate":"2026-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13356838/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148430537","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":"Preoperative Prediction of Glypican-3 Expression in Hepatocellular Carcinoma Using Sonazoid Contrast-Enhanced Ultrasound Radiomics.","authors":"Shangman Yang, Zerong Huang, Wei Zheng, Lingling Li, Yao Xue, Ruhai Zou, Chuan Peng","doi":"10.2147/JHC.S610969","DOIUrl":"10.2147/JHC.S610969","url":null,"abstract":"<p><strong>Objective: </strong>To develop and validate a noninvasive radiomics approach based on Sonazoid contrast-enhanced ultrasound (CEUS) for preoperative prediction of Glypican-3 (GPC3) status in solitary hepatocellular carcinoma (HCC) patients and to evaluate its association with early recurrence-free survival (RFS).</p><p><strong>Materials and methods: </strong>This diagnostic accuracy study retrospectively included 278 solitary HCC patients at a grade A Tertiary Hospital (2020.3-2024.1). Radiomics features were extracted from CEUS images, and robust feature selection was performed using minimum redundancy-maximum relevance (mRMR) and least absolute shrinkage and selection operator (LASSO). A logistic-regression radiomics model was trained and internally validated using a pathologic reference standard. A hybrid model combining the radiomics signature with significant clinical variables was then constructed. Model performance was assessed by the area under the receiver operating characteristic curve (AUC). RFS was compared using the log‑rank test.</p><p><strong>Results: </strong>Among 278 patients (median age, 57 years; IQR, 49-64 years; 232 males), alpha-fetoprotein (AFP) > 200 ng/mL and the radiomics score were independent predictors of GPC3 positivity. The hybrid model integrating CEUS-based radiomics features and AFP achieved AUCs of 0.81 (95% CI: 0.74-0.89) and 0.78 (95% CI: 0.66-0.89) in the training and validation sets, respectively, significantly outperforming the radiomics model (AUC 0.74 (95% CI: 0.65-0.83) and 0.67 (95% CI: 0.52-0.83), both <i>p</i> < 0.01). The radiomics score was not significantly associated with early RFS (<i>p</i> > 0.05).</p><p><strong>Conclusion: </strong>A hybrid model integrating CEUS-based radiomics features and AFP, developed in solitary HCC, shows potential for non-invasive preoperative prediction of GPC3 positive expression in HCC, which may facilitate personalized preoperative treatment planning for these patients. However, it did not predict early recurrence-free survival, and its prognostic value was not demonstrated in this study.</p>","PeriodicalId":15906,"journal":{"name":"Journal of Hepatocellular Carcinoma","volume":"13 ","pages":"610969"},"PeriodicalIF":3.9,"publicationDate":"2026-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13332783/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148391136","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}