Journal of Hepatocellular Carcinoma最新文献

{"title":"Investigating the Expression and Function of <i>PPP2R1A</i> in Hepatocellular Carcinoma: A Multi-Omics Analysis with in vitro Validation.","authors":"Jinna Tan, Yangling Zeng, Hemeng Wu, Yuni Liang, Yunshan Qiu, Qiulian Mo, Yuzhen Luo, Jiaqian He, Yunyong Wang, Hui Yin, Peipei Chen, Mingfen Li, Hongsheng Lin","doi":"10.2147/JHC.S641006","DOIUrl":"https://doi.org/10.2147/JHC.S641006","url":null,"abstract":"<p><strong>Background: </strong>Hepatocellular carcinoma (HCC) remains difficult to diagnose early and to treat effectively. Protein Phosphatase 2A Regulatory Subunit Aα (<i>PPP2R1A</i>), the scaffolding (Aα) subunit of the PP2A holoenzyme, is altered in several cancer types, but its expression pattern, functional significance, and translational relevance in HCC are incompletely understood.</p><p><strong>Methods: </strong>Public transcriptomic, single-cell, and spatial transcriptomic datasets (TCGA-LIHC, GTEx, GEO, ICGC-LIHC, HPA, TISCH2) and drug-sensitivity databases were integrated to characterize <i>PPP2R1A</i> expression and its associations with survival, biological pathways, and tumor immune infiltration in HCC. Functional effects of <i>PPP2R1A</i> knockdown were assessed in Huh7 cells by RT-qPCR, CCK-8, Transwell, flow-cytometric cell-cycle, and β-galactosidase assays.</p><p><strong>Results: </strong><i>PPP2R1A</i> was significantly overexpressed in HCC tissues relative to normal liver and was also elevated across several other cancer types. High <i>PPP2R1A</i> expression was associated with shorter overall and disease-specific survival in Kaplan-Meier analysis, although it was not an independent prognostic factor after multivariate adjustment (hazard ratio [HR] = 1.051, p = 0.789). <i>PPP2R1A</i> expression correlated positively with transcriptional programs related to cell cycle, MYC, EGFR, MAPK, and WNT signaling, and negatively with p53 pathway activity. At single-cell and spatial resolution, <i>PPP2R1A</i> was enriched in malignant cells and in tumor regions, and its expression correlated with the abundance of several computationally inferred immune cell populations. <i>PPP2R1A</i> knockdown in Huh7 cells reduced proliferation and invasion, induced G2-phase arrest, and decreased MYC, CDK1, and CCNB1 mRNA expression without inducing senescence. Drug-sensitivity screens suggested candidate agents, such as AT-7519, that warrant further investigation in <i>PPP2R1A</i>-high HCC.</p><p><strong>Conclusion: </strong><i>PPP2R1A</i> is consistently overexpressed in HCC and contributes to the malignant phenotype at least partly through cell-cycle regulation. These findings are hypothesis-generating, and the potential diagnostic, prognostic, or therapeutic value of <i>PPP2R1A</i> in HCC requires dedicated prospective and functional validation.</p>","PeriodicalId":15906,"journal":{"name":"Journal of Hepatocellular Carcinoma","volume":"13 ","pages":"641006"},"PeriodicalIF":3.9,"publicationDate":"2026-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13744179/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149370871","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":"A Laboratory-Based Triage Model for Hepatocellular Carcinoma Early-Detection Pathways in Hospital-Evaluated Populations: Development and External Validation.","authors":"Liqiao Zhang, Xiaozhen Xu, Xingfen Zhang, Miao Cheng, Guosheng Gao, Xijie Lai","doi":"10.2147/JHC.S645422","DOIUrl":"https://doi.org/10.2147/JHC.S645422","url":null,"abstract":"<p><strong>Background: </strong>Hepatocellular carcinoma (HCC) remains a major clinical and health-system burden in East and South-East Asia, and early-detection pathways remain vulnerable when alpha-fetoprotein (AFP) is low or non-informative. We developed and externally validated Extended-7 as a routine laboratory-based triage aid to prioritize diagnostic attention within hospital HCC early-detection and referral pathways.</p><p><strong>Methods: </strong>This two-center retrospective study evaluated a hospital-based laboratory triage model in a Ningbo development cohort (n=523; 267 HCC and 256 controls) and an independent Lihuili external-validation cohort (n=269; 150 HCC and 119 controls). Using these data, we developed and validated an HCC risk-stratification model intended to support prioritization for further diagnostic evaluation, not stand-alone diagnosis or replacement of imaging/pathology. Discrimination, calibration, decision-curve profiles, cohort-specific Youden operating characteristics, and exploratory AFP-low subgroups were evaluated against AFP, AFP-L3, PIVKA-II, a three-marker model, GALAD, and ASAP.</p><p><strong>Results: </strong>Extended-7 combined ln(AFP+1), AFP-L3, ln(PIVKA-II+1), age, sex, platelet count, and albumin. Extended-7 achieved a 5-fold cross-validated AUC of 0.900 (95% CI, 0.871-0.924) in the development cohort and an external AUC of 0.738 (95% CI, 0.681-0.793). In external validation, discrimination was higher than GALAD (AUC 0.694; DeLong p=0.006), ASAP (AUC 0.643; p<0.001), and the three-marker model (AUC 0.602; p<0.001). At the external Youden cutoff, Extended-7 identified 119 of 150 HCC cases while classifying 47 of 119 non-HCC controls as false-positive triage referrals. In the external AFP-low subgroup, Extended-7 achieved an AUC of 0.808; the paired bootstrap comparison vs GALAD did not reach conventional statistical significance. External calibration was weak (Brier score 0.224; calibration slope 0.262).</p><p><strong>Conclusions: </strong>Extended-7 showed moderate external discrimination and may support laboratory-based prioritization in hospital HCC early-detection pathways, including patients with low AFP, while subgroup findings remain exploratory. However, transported probabilities require local recalibration, and prospective multicenter evaluation of referral thresholds, decision impact, and cost-effectiveness is needed before clinical implementation.</p>","PeriodicalId":15906,"journal":{"name":"Journal of Hepatocellular Carcinoma","volume":"13 ","pages":"645422"},"PeriodicalIF":3.9,"publicationDate":"2026-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13744181/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149370870","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":"Histotripsy for Hepatocellular Carcinoma in Asia-Pacific: Current Evidence, Evidence Gaps, and Future Research Priorities.","authors":"Ming-Feng Chiang, Shyh-Chyi Chang, Ben-Chang Shia, Yi-Si Liu, Chiung-Yun Lo, Hai-Pei Hsu, Szu-Yuan Wu","doi":"10.2147/JHC.S630056","DOIUrl":"10.2147/JHC.S630056","url":null,"abstract":"<p><strong>Background: </strong>Histotripsy is a non-thermal focused-ultrasound ablation technology that produces mechanical tissue fractionation through controlled acoustic cavitation. In hepatocellular carcinoma (HCC), its relevance remains investigational, particularly in settings where conventional thermal ablation may be constrained by heat-sink effects, vascular or biliary proximity, limited hepatic reserve, or the need for repeated local therapy. This review evaluates the evidence without assuming an established clinical role.</p><p><strong>Methods: </strong>We performed a structured narrative review with systematic literature identification and evidence classification. The structured core search covered PubMed/MEDLINE, Scopus, Embase, and Google Scholar from database inception through February 2026; a targeted update through 20 September 2026 was used to identify newly published clinical studies, safety reports, and reviews. Evidence was classified as direct HCC, mixed liver-tumour, non-HCC clinical extrapolation, or preclinical/mechanistic evidence.</p><p><strong>Results: </strong>Evidence remains early-stage and heterogeneous. #HOPE4LIVER reported 95.5% technical success and 6.8% major complications in mixed primary and metastatic liver-tumour cohorts, with incomplete HCC-specific outcome reporting. The Hong Kong prospective cohort included 19 patients with HCC, all Child-Pugh A, and reported 95% technical success, 82.5% complete response at 1 month, and no grade III or higher complications. Real-world reports also document vascular injury, haemorrhage, and pseudoaneurysm, underscoring that relative resistance of collagen-rich structures should not be interpreted as proven vascular or biliary safety.</p><p><strong>Conclusion: </strong>Histotripsy should be regarded as an investigational non-thermal ablation technology for HCC. Current data support technical feasibility and preliminary clinical signals, but not superiority, equivalence, or guideline-defined positioning relative to established therapies. HCC-specific prospective cohorts, standardized safety reporting, long-term oncological outcomes, and comparative studies are required.</p>","PeriodicalId":15906,"journal":{"name":"Journal of Hepatocellular Carcinoma","volume":"13 ","pages":"630056"},"PeriodicalIF":3.9,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13738221/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149342375","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":"Rare Case Report: Therapy-Related Acute Promyelocytic Leukemia (t-APL) in a Young Non-HBV Female After TACE Plus Sintilimab-Lenvatinib for HCC - A Clinical Alert and Literature Review.","authors":"Rong Yu, Xulin Shi, Huaxi Fan, Guishu Wu, Jing Zhang, Xiangyu Deng, Xiaolong Liu, Mingyue Rao, Jianwen Zhang","doi":"10.2147/JHC.S656165","DOIUrl":"10.2147/JHC.S656165","url":null,"abstract":"<p><strong>Background: </strong>Transarterial chemoembolization (TACE) combined with PD-1 immune checkpoint inhibitor plus lenvatinib is a standard first-line therapy for unresectable hepatocellular carcinoma (HCC). Therapy-related acute promyelocytic leukemia (t-APL) is a rare but life-threatening secondary hematologic malignancy. Reports of t-APL following this triple regimen in non-HBV young female HCC patients remain extremely limited.</p><p><strong>Methods: </strong>We report a 30-year-old non-HBV female patient with moderately-differentiated HCC diagnosed incidentally in early pregnancy, who received pregnancy termination followed by oxaliplatin-fluorouracil-based TACE, then sintilimab plus lenvatinib maintenance. Clinical, laboratory, bone marrow, imaging and histopathological data were collected. We further performed a systematic review of published t-APL cases in HCC patients treated with targeted-immune therapy up to May 2026.</p><p><strong>Results: </strong>Approximately 12 months after treatment initiation, the patient developed oral mucosal ecchymosis, fatigue and anorexia. Serial blood tests demonstrated progressive thrombocytopenia and increasing circulating promyelocytes. Bone-marrow examination and FISH confirmed PML/RARA-positive t-APL. Due to economic burden, the patient refused standard all-trans retinoic acid (ATRA) plus arsenic trioxide and died 3 months after t-APL diagnosis. Combined with 11 previously reported cases (total n=12 globally), the median latency from targeted-immunotherapy commencement to t-APL onset was 11 months (range 6-18 months). Pathogenesis may involve synergistic genotoxic injury from TACE chemotherapy, PD-1-mediated immune dysregulation, lenvatinib-associated myelotoxicity and host individual susceptibility.</p><p><strong>Conclusion: </strong>t-APL is a rare fatal complication of TACE plus sintilimab-lenvatinib for HCC, mostly occurring within 1 year of therapy initiation. Mandatory monthly hematologic monitoring is required during this high-risk window. Prompt bone-marrow evaluation and PML/RARA fusion testing should be performed for unexplained cytopenia or circulating immature myeloid cells to enable timely ATRA-arsenic-based intervention.</p>","PeriodicalId":15906,"journal":{"name":"Journal of Hepatocellular Carcinoma","volume":"13 ","pages":"656165"},"PeriodicalIF":3.9,"publicationDate":"2026-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13730098/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149321929","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":"Biopsychosocial Perioperative Care, Perioperative Stress, and Peripheral T-Cell Subset Recovery After Laparoscopic Hepatectomy for Hepatocellular Carcinoma: A Retrospective Propensity-Weighted Cohort Study.","authors":"Huan Ma, Meijie Wang, Linna Wang, Hongxia Song","doi":"10.2147/JHC.S649665","DOIUrl":"10.2147/JHC.S649665","url":null,"abstract":"<p><strong>Background: </strong>Laparoscopic hepatectomy for hepatocellular carcinoma (HCC) imposes substantial surgical and psychological stress, with potential neuroendocrine and immune consequences. Whether integrated biopsychosocial perioperative care is associated with differences across several perioperative domains remains unclear.</p><p><strong>Objective: </strong>This study aimed to evaluate the association of a structured biopsychosocial (BPS) perioperative programme with psychological distress, stress hormones, cellular immunity, postoperative recovery, sleep, safety, and 18-month oncological outcomes after laparoscopic hepatectomy for HCC.</p><p><strong>Methods: </strong>This single-centre retrospective cohort included 343 consecutive patients treated between January 2022 and January 2025; 169 received BPS care plus conventional management and 174 received conventional care alone. Anxiety, depression, stress hormones, T-lymphocyte subsets, recovery, pain, opioid use, sleep, complications, recurrence, and survival were assessed longitudinally. Linear mixed-effects models and propensity-score overlap weighting with multivariable adjustment were used; time-to-event outcomes were analysed using Cox models. The anxiety (Self-Rating Anxiety Scale, SAS) and depression (Self-Rating Depression Scale, SDS) trajectories were prespecified as the co-primary outcomes. Propensity-score overlap weighting used covariates measured before programme allocation, and multiplicity was controlled within prespecified outcome families using the Benjamini-Hochberg false-discovery-rate procedure.</p><p><strong>Results: </strong>After weighting, all measured covariates were balanced (maximum standardised mean difference 0.03). SAS and SDS trajectories favoured BPS care (group × time, both P<0.001), with adjusted discharge differences of -4.3 and -2.7 points, respectively. At postoperative day 7, the adjusted CD4+/CD8+ difference was +0.26 (95% CI 0.20-0.32). Length of stay was shorter by 1.1 days (95% CI -1.6 to -0.7), and 1-month PSQI was lower by 1.45 points (95% CI -1.78 to -1.12). Thirty-day complications, recurrence, and mortality were not statistically different. Peripheral-blood T-cell subset proportions index circulating composition and may not represent tissue or tumour-microenvironment antitumour immunity. After false-discovery-rate correction, all co-primary and secondary endpoints remained significant, whereas the safety and 18-month oncological endpoints did not.</p><p><strong>Conclusion: </strong>Structured BPS perioperative care was associated with favourable differences across several domains of postoperative recovery after laparoscopic hepatectomy for HCC. These findings support prospective multicentre randomised evaluation of integrated biopsychosocial care. The findings support integrated biopsychosocial care as a complement to, not a replacement for, established enhanced-recovery pathways.</p>","PeriodicalId":15906,"journal":{"name":"Journal of Hepatocellular Carcinoma","volume":"13 ","pages":"649665"},"PeriodicalIF":3.9,"publicationDate":"2026-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13730071/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149321925","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":"A Combined Ki-67 and Microvascular Invasion Score Predicts Early Recurrence and Survival After Hepatectomy for HCC.","authors":"Wenxiang Jin, Shaoqi Zu, Hong Zhu, Ning Jiang, Chao Yang","doi":"10.2147/JHC.S658050","DOIUrl":"10.2147/JHC.S658050","url":null,"abstract":"<p><strong>Background: </strong>Both Ki-67 proliferation index and microvascular invasion (MVI) are independent predictors of postoperative recurrence in hepatocellular carcinoma (HCC), but their combined prognostic value remains unclear. This study aimed to develop and internally validate a Combined Ki-67 and MVI Score (CKMS) for predicting recurrence and survival after HCC resection.</p><p><strong>Methods: </strong>A total of 255 HCC patients who underwent curative resection were prospectively enrolled. Based on postoperative pathological findings, the CKMS was constructed by summing graded Ki-67 (0-2 based on 30% and 50% cutoffs) and MVI (0-2 based on M0/M1/M2), yielding a score of 0-4, and patients were stratified into low-risk (0-1), intermediate-risk (2-3), and high-risk (4) groups. Recurrence-free survival (RFS) and overall survival (OS) were analyzed using Kaplan-Meier and Cox proportional hazards models, adjusting for BCLC stage, AFP, age, and adjuvant therapies. Internal validation was performed using bootstrap resampling.</p><p><strong>Results: </strong>The median follow-up duration was 19.0 months (95% CI 16.7-21.3 months). During the follow-up period, 81 patients (31.8%) developed recurrence and 69 patients (27.1%) died. Multivariable Cox regression showed that the CKMS high-risk group was an independent risk factor for both RFS (HR=2.766, 95% CI 1.489-5.139, P<0.001) and OS (HR=8.324, 95% CI 3.768-18.386, P<0.001), and the intermediate-risk group was also significantly associated with OS (HR=2.905, 95% CI 1.550-5.446, P<0.001). BCLC stage C, AFP >11.31 ng/mL, and liver function grade B/C at 1 month post-surgery were also independent prognostic factors. Internal validation and sensitivity analyses showed consistent prognostic effects of the CKMS.</p><p><strong>Conclusion: </strong>The CKMS, based on routine pathological markers, may serve as a simple tool for postoperative risk stratification and individualized follow-up in HCC, but its clinical utility requires external validation.</p>","PeriodicalId":15906,"journal":{"name":"Journal of Hepatocellular Carcinoma","volume":"13 ","pages":"658050"},"PeriodicalIF":3.9,"publicationDate":"2026-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13726612/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149321924","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":"A Case of Advanced Hepatocellular Carcinoma with Macrovascular Invasion and Lung Metastases Achieving Pathological Complete Remission Following Sequential Multimodal Therapy: A Case Report.","authors":"Xiongxiong Han, Yaoping Pang, Shulin Xu, Liangbin Ma, Yong Wang, Jianwei Qin, Long Yan","doi":"10.2147/JHC.S643390","DOIUrl":"https://doi.org/10.2147/JHC.S643390","url":null,"abstract":"<p><strong>Background: </strong>Hepatocellular carcinoma (HCC) has a high incidence worldwide, and most patients are diagnosed at the intermediate or advanced stages; 10%-40% lose the opportunity for surgery due to concomitant vascular invasion. A triple-therapy regimen combining transarterial chemoembolization (TACE)/hepatic arterial infusion chemotherapy (HAIC) with targeted therapy and immunotherapy offers promise for conversion therapy in advanced HCC; however, its efficacy is limited in high-burden patients with concomitant major vascular invasion and extrahepatic metastases, and a quadruple-therapy regimen for conversion therapy remains to be explored.</p><p><strong>Case summary: </strong>This report describes a 33-year-old male patient with Barcelona Clinic Liver Cancer-C (BCLC-C) stage HCC, accompanied by cancer emboli in the inferior vena cava and portal vein, as well as lung metastases, for whom there were no indications for surgery. Following a Multidisciplinary Team (MDT) discussion, the patient was initially treated with a triple-agent regimen of TACE combined with apatinib and camrelizumab for one cycle (21 days per cycle). The response was limited, and a new tumor thrombus developed in the right hepatic vein; treatment was therefore adjusted to a quadruple-agent regimen of TACE-HAIC combined with apatinib and camrelizumab for three cycles (21 days per cycle). The patient achieved a partial response according to the modified Response Evaluation Criteria in Solid Tumors (mRECIST), and alpha-fetoprotein (AFP) levels decreased significantly. The patient subsequently underwent partial hepatectomy combined with inferior vena cava reconstruction, and postoperative pathology confirmed a pathological complete response (pCR). As of June 30, 2026, follow-up has shown no evidence of tumor recurrence, tumor markers are within normal limits, and disease-free survival (DFS) has exceeded 12 months.</p><p><strong>Conclusion: </strong>This case suggests that, for patients with advanced HCC complicated by major vascular invasion and extrahepatic metastases who are carefully selected by an MDT, a sequential four-drug regimen may lead to successful conversion. These results are based on a single case observation and may serve as a basis for research hypotheses; however, the efficacy and safety of this approach still require validation through prospective studies.</p>","PeriodicalId":15906,"journal":{"name":"Journal of Hepatocellular Carcinoma","volume":"13 ","pages":"643390"},"PeriodicalIF":3.9,"publicationDate":"2026-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13724043/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149321923","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 Sequential Radiotherapy and Immune Checkpoint Inhibitors for Advanced Hepatocellular Carcinoma: A Single-Center PSM Retrospective Cohort Study.","authors":"Huaxi Fan, Rong Yu, Guishu Wu, Jing Zhang, Xiangyu Deng, Xiaolong Liu, Mingyue Rao, Kun He, Jianwen Zhang","doi":"10.2147/JHC.S645600","DOIUrl":"https://doi.org/10.2147/JHC.S645600","url":null,"abstract":"<p><strong>Background: </strong>The optimal administration sequence of immune checkpoint inhibitors (ICIs) and radiotherapy (RT) for advanced hepatocellular carcinoma (HCC) remains unclear. This study compared the efficacy and safety of ICIs administered before vs after RT in advanced HCC patients.</p><p><strong>Methods: </strong>This single-center, retrospective cohort study employed propensity score matching (PSM). Patients with advanced HCC receiving sequential ICI-RT therapy (with or without concurrent targeted therapy) from January 2020 to December 2024 were divided into ICI+RT (ICI before RT, n=96) and RT+ICI (RT before ICI, n=100) groups, with treatment interval ≤14 days. Approximately half of patients in each group received concurrent targeted agents. Primary endpoints were progression-free survival (PFS) and overall survival (OS); secondary endpoints included objective response rate (ORR), disease control rate (DCR), and treatment-related adverse events (TRAEs).</p><p><strong>Results: </strong>After 1:1 PSM, 77 paired patients were analyzed (median follow-up 19.4 months). The RT+ICI group demonstrated longer median PFS (7.8 vs 5.6 months, HR 1.551, 95% CI 1.038-2.317, p=0.031), higher ORR (74.0% vs 54.5%, p=0.019), and lower progressive disease rate as best response (0.0% vs 10.4%, p=0.006). Median OS showed numerical but non-significant improvement (14.1 vs 12.5 months, HR 1.112, 95% CI 0.746-1.657, p=0.600). Grade 3-4 thrombocytopenia was more frequent in RT+ICI (42.9% vs 20.8%, p=0.006). Longitudinal neutrophil-to-lymphocyte ratio and lymphocyte-to-monocyte ratio changes suggested potential immune-priming effects of RT when administered before ICI.</p><p><strong>Conclusions: </strong>In this retrospective PSM cohort, RT followed by ICI was associated with improved PFS and tumor responses in advanced HCC, alongside manageable toxicity. These findings suggest potential value of RT as immune priming before ICI, though prospective validation is needed given the observational nature and single-center design of this study.</p>","PeriodicalId":15906,"journal":{"name":"Journal of Hepatocellular Carcinoma","volume":"13 ","pages":"645600"},"PeriodicalIF":3.9,"publicationDate":"2026-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13724073/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149321927","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":"Conversion Surgery After HAIC-Based Combination Therapy with Targeted Therapy and Immune Checkpoint Inhibitors for Initially Unresectable Hepatocellular Carcinoma: A Retrospective Cohort Study.","authors":"Xiaolong Zhang, Jun Hu, Haoming Lan, Xianfeng Shen, Meng Zhou, Youyou Tian","doi":"10.2147/JHC.S644129","DOIUrl":"https://doi.org/10.2147/JHC.S644129","url":null,"abstract":"<p><strong>Background: </strong>For selected patients whose initially unresectable hepatocellular carcinoma (HCC) responds to hepatic arterial infusion chemotherapy (HAIC)-based combination treatment, conversion surgery may provide an opportunity for curative-intent management. We quantified the frequency of conversion surgery, examined factors associated with surgical conversion, and assessed survival and pathological outcomes using analyses that accounted for immortal time bias.</p><p><strong>Methods: </strong>We conducted a single-center retrospective cohort study of 216 patients with initially unresectable HCC who received HAIC together with targeted therapy and immune checkpoint blockade from September 2020 through June 2023. The relationship between conversion surgery and survival was examined with time-dependent Cox regression and a prespecified 180-day landmark analysis. Two hepatopathologists independently assessed the pathological response.</p><p><strong>Results: </strong>47 (21.8%) patients underwent conversion surgery, and 16 (34.0%) achieved pathological complete response (pCR). Median overall survival (OS) was 22.7 months (95% confidence interval [CI], 21.1-25.8), and median progression-free survival (PFS) was 13.7 months (95% CI, 10.9-16.2). In adjusted 180-day landmark analyses including 211 patients for OS and 166 patients for PFS, conversion surgery was associated with lower hazards of death (hazard ratio [HR], 0.30; 95% CI, 0.16-0.59; <i>P</i> < 0.001) and progression or death (HR, 0.32; 95% CI, 0.16-0.64; <i>P</i> = 0.001); time-dependent Cox models produced consistent findings. Albumin ≥ 35 g/L was associated with higher odds of conversion surgery (odds ratio [OR], 5.47; 95% CI, 1.75-17.06), whereas multifocal tumors were associated with lower odds (OR, 0.13; 95% CI, 0.06-0.29). Among resected patients, pCR was associated with favorable postoperative outcomes in exploratory unadjusted analyses.</p><p><strong>Conclusion: </strong>47 of 216 patients (21.8%) underwent conversion surgery after HAIC-based combination therapy. Conversion surgery was associated with favorable OS and PFS after accounting for treatment timing. However, causal inference remains limited by residual confounding and treatment-selection bias in this retrospective study. The prognostic value of pCR requires validation in larger prospective cohorts.</p>","PeriodicalId":15906,"journal":{"name":"Journal of Hepatocellular Carcinoma","volume":"13 ","pages":"644129"},"PeriodicalIF":3.9,"publicationDate":"2026-10-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13723248/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149321926","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":"Multilevel Determinants of Liver Cancer Screening Uptake in Community-Based High-Risk Populations in Chongqing, China: A Prospective Cohort Study.","authors":"Bibo Li, Zhikai Yu, Yan Zhang, Qiucheng Li, Xiu Liu, Qing Guo, Hong Zhou, Jia Du, Mei He","doi":"10.2147/JHC.S641810","DOIUrl":"https://doi.org/10.2147/JHC.S641810","url":null,"abstract":"<p><strong>Background: </strong>Evidence on the uptake and determinants of liver cancer screening in Southwest China remains limited. This study aimed to assess the participation rate, influencing factors, and screening outcomes among high-risk individuals in a population-based liver cancer screening program.</p><p><strong>Methods: </strong>A community-based screening program was conducted across 18 districts or counties in Chongqing, China, from October 2013 to October 2022. High-risk individuals identified through a risk assessment system were invited to receive alpha-fetoprotein (AFP) testing and abdominal ultrasonography. A generalized linear mixed model (GLMM) was applied to identify individual-level and structural factors associated with screening uptake. Reasons for non-participation and liver cancer detection rates were also assessed.</p><p><strong>Results: </strong>Among the 369,393 individuals who completed the risk assessment, 37,381 were identified as being at high-risk for liver cancer. After exclusions, 34,647 were included in the final analysis. Of these, 14,062 underwent screening, yielding an uptake rate of 40.59%. Screening participation was significantly associated with younger age, occupational exposures, alcohol consumption, lower levels of physical activity, hepatitis B infection, history of liver cirrhosis, comorbidities, and family history of liver cancer. At the structural level, developed status, use of multiple mobilization strategies, and receiving allowances were positively associated with uptake. Among 20,585 non-participants, the most frequently reported barriers included no symptoms (93.61%), fear of diagnosis (92.60%), and lack of knowledge about cancer prevention and treatment (89.30%). Liver cancer was detected in 14 of the screened individuals, corresponding to a detection rate of 0.10%.</p><p><strong>Conclusion: </strong>Participation in liver cancer screening is shaped by a combination of individual and structural factors. Targeted interventions addressing key barriers (such as low risk perception, fear, and knowledge gaps) and structural factors (such as diversified mobilization and financial incentives) may help improve screening uptake among the high-risk populations.</p>","PeriodicalId":15906,"journal":{"name":"Journal of Hepatocellular Carcinoma","volume":"13 ","pages":"641810"},"PeriodicalIF":3.9,"publicationDate":"2026-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13722542/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149321928","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}