Journal of Hepatocellular Carcinoma最新文献

{"title":"Fatty Acid Degradation (FAD) Subtype-Informed Treatment Allocation in Unresectable Hepatocellular Carcinoma (FAD-HCC-01): Protocol for a Prospective Multicentre Proof-of-Concept Study.","authors":"Yuan Cheng, Binghua Li, Decai Yu","doi":"10.2147/JHC.S608436","DOIUrl":"10.2147/JHC.S608436","url":null,"abstract":"<p><strong>Background: </strong>Hepatocellular carcinoma (HCC) exhibits substantial biological and metabolic heterogeneity, contributing to variable therapeutic responses in unresectable disease. Although immune checkpoint inhibitors combined with anti-angiogenic agents have improved outcomes, treatment selection remains largely empirical because validated predictive biomarkers are lacking. Recent multi-omics studies have identified fatty acid degradation (FAD)-related transcriptional signatures that classify HCC into distinct metabolic subtypes with different immune microenvironment characteristics and therapeutic vulnerabilities. Retrospective analyses suggest that F1/F2 subtypes may derive greater benefit from immune checkpoint inhibitor-based systemic therapy, whereas F3 tumours may be more responsive to transarterial chemoembolisation (TACE). However, whether FAD-based metabolic stratification can prospectively inform treatment allocation remains unknown.</p><p><strong>Methods: </strong>FAD-HCC-01 is a prospective, multicentre, open-label proof-of-concept Phase II study designed to evaluate the feasibility and preliminary clinical activity of FAD-informed treatment allocation in patients with unresectable HCC. Eligible patients with Barcelona Clinic Liver Cancer stage B or C disease and no prior systemic therapy will undergo baseline tumour transcriptomic profiling to determine FAD subtype. Patients with F1/F2 tumours will receive camrelizumab plus rivoceranib, whereas patients with F3 tumours will receive TACE combined with camrelizumab and rivoceranib. Eighty-six patients will be enrolled, with 43 in each biomarker-defined cohort. The primary endpoint is objective response rate according to RECIST version 1.1. Secondary endpoints include objective response rate by mRECIST, disease control rate, progression-free survival, overall survival, duration of response, conversion to curative treatment, and safety. Exploratory analyses will assess concordance between MRI-derived proton density fat fraction and transcriptomic FAD classification.</p><p><strong>Conclusion: </strong>This proof-of-concept study will prospectively assess whether FAD-based metabolic subtyping can inform treatment allocation in unresectable HCC. The results may provide early evidence supporting metabolism-informed precision therapy and the design of future biomarker-guided clinical trials.</p>","PeriodicalId":15906,"journal":{"name":"Journal of Hepatocellular Carcinoma","volume":"13 ","pages":"608436"},"PeriodicalIF":3.9,"publicationDate":"2026-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13186218/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147981987","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 Mouse in vivo Model Mimicking MASH-Related HCC Pathogenesis.","authors":"Tianxiao Zheng, Zhi Pei, Enze Cui, Luyuan Zhu, Juan Du, Changquan Ling","doi":"10.2147/JHC.S593754","DOIUrl":"10.2147/JHC.S593754","url":null,"abstract":"<p><strong>Background/objectives: </strong>Hepatocellular carcinoma (HCC) derived from metabolic dysfunction-associated steatotic liver disease (MASH) has garnered increasing attention. To develop improved treatment strategies, it is crucial to comprehend its pathological processes. However, existing models frequently neglect to integrate key molecular features of human MASH-related HCC or require excessively prolonged experimental timelines. Our objective was to establish a novel murine model that facilitates accelerated and accurate progression by combining chronic metabolic stress with specific oncogenic drivers.</p><p><strong>Methods: </strong>A murine model was developed by subjecting mice to a choline-deficient, high-fat diet (CDAA-HFD) in conjunction with hydrodynamic transfection of NRAS^G12V/AKT oncogenes. Disease progression was evaluated through histopathological analysis, while molecular fidelity was assessed by comparing the liver transcriptomic profile of the model to that of human MASH-related HCC.</p><p><strong>Results: </strong>Results: Histological examination demonstrated that the combination of CDAA-HFD and NRASG12V/AKT expedited the transition from steatohepatitis to hepatocellular carcinoma (HCC), with malignant lesions apparent at the conclusion of the study. Notably, comparative transcriptomic analysis indicated a significant molecular concordance between the animal model and human MASH-related HCC. Dysregulation was prominently observed in pathways regulating lipid metabolism (PPAR signaling, fatty acid metabolism), extracellular matrix remodeling (focal adhesion), and oncogenic signaling (PI3K-Akt pathway).</p><p><strong>Conclusion: </strong>Conclusions: Our integrated dietary and genetic model accurately replicates the essential pathological and molecular characteristics of human MASH-related HCC. This high level of fidelity confirms its value as a reliable preclinical platform for exploring disease mechanisms and assessing therapeutic strategies for this increasingly prevalent malignancy.</p>","PeriodicalId":15906,"journal":{"name":"Journal of Hepatocellular Carcinoma","volume":"13 ","pages":"593754"},"PeriodicalIF":3.9,"publicationDate":"2026-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13185970/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147982012","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":"Identification of a Prognostic Gene Signature Based on Lenvatinib Resistance in Hepatocellular Carcinoma with Functional Validation of the Key Gene CPB2.","authors":"Kan Liu, Fei Cheng, Chao Li, Simiao Cheng, Junyan Wei, Jianbing Wu, Shenglan Huang","doi":"10.2147/JHC.S579244","DOIUrl":"10.2147/JHC.S579244","url":null,"abstract":"<p><strong>Background: </strong>Hepatocellular carcinoma (HCC) is a prevalent and lethal form of liver cancer that necessitates the exploration of innovative strategies due to the limitations of current therapies, including high recurrence rates and drug resistance.</p><p><strong>Methods: </strong>Lenvatinib-resistant Huh7-LR and PLC/PRF/5-LR cell lines were established. RNA sequence analysis was performed to identify differentially expressed genes associated with lenvatinib resistance in HCC tissues. A prognostic model was constructed using Cox regression analysis incorporating eight prognosis-related genes. A nomogram was developed by combining clinical factors and risk scores. Functional validation of the key gene, CPB2, was performed to explore its role in HCC progression and lenvatinib resistance.</p><p><strong>Results: </strong>Lenvatinib-resistant Huh7-LR and PLC/PRF/5-LR cell lines exhibited significant resistance indices of 4.59 and 4.37, respectively. RNA sequence analysis revealed 82 genes associated with lenvatinib resistance that were differentially expressed in HCC tissues. The prognostic model stratified patients into high-risk and low-risk groups with significantly distinct overall survival outcomes (p = 3.057e-05). The nomogram demonstrated high concordance in predicting survival probabilities (AUC = 0.78). CPB2 has emerged as a core gene linked to lenvatinib resistance; low expression of CPB2 in HCC tissues is associated with poor prognosis and promotes HCC progression and lenvatinib resistance via inhibition of the MAPK signaling pathway.</p><p><strong>Conclusion: </strong>These findings underscore the importance of understanding lenvatinib resistance mechanisms, providing a foundation for future therapeutic strategies targeting CPB2, and advancing personalized treatment approaches for HCC.</p>","PeriodicalId":15906,"journal":{"name":"Journal of Hepatocellular Carcinoma","volume":"13 ","pages":"579244"},"PeriodicalIF":3.9,"publicationDate":"2026-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13182753/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147972988","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 Reproducible MRI-Based Quantitative Feature for Differentiating Dysplastic Nodules from Hepatocellular Carcinoma: A Multicenter Retrospective Study.","authors":"Cheng Zhang, Shuyi Xie, Chuangxin Wang, Tuo Ren, Xi Zhong, Yixin Zhang, Shuo Li, Weijie Wu, Ying Sun, Chuanmiao Xie","doi":"10.2147/JHC.S609066","DOIUrl":"10.2147/JHC.S609066","url":null,"abstract":"<p><strong>Purpose: </strong>High percentage of well-differentiated hepatocellular carcinoma (HCC) was radiologically misdiagnosed as dysplastic nodule (DN), which may lead to delay in treatment. This study aims to develop a reproducible feature for DN/HCC differentiation.</p><p><strong>Patients and methods: </strong>This study included patients which underwent curative hepatectomy or biopsy from four hospitals in China. The study population was divided into internal training cohort, internal test cohort, external validation cohort. Energy value was extracted from arterial and hepatobiliary phase lesion to represent intensity. Hepatobiliary-Arterial Intensity Ratio (HAIR) was calculated to demonstrate the intensity change from cirrhotic nodule to HCC. GPC3 (Glypican-3) was analyzed to validate HAIR's relation with nodule differentiation. Supporting Vector Machine (SVM) was built as a comparative model. Area Under the Curve (AUC) was used to evaluate and compare the predictive efficacy of HAIR.</p><p><strong>Results: </strong>A total of 116 patients with 120 lesions (52 dysplastic nodules and 68 hepatocellular carcinomas) were included. The AUC of HAIR and SVM for differentiating DN and HCC in internal test cohort were 0.824 (95% CI, 0.662-0.986, <i>p</i><0.01) and 0.733 (95% CI, 0.593-0.872, <i>p</i><0.01), respectively. The cut-off value of the HAIR logistic regression based on training cohort was 0.46, which was subsequently validated in the external validation group. The AUC of HAIR in external validation cohort was 0.667. The correlation between HAIR and GPC3 showed statistical significance (<i>p</i><0.01).</p><p><strong>Conclusion: </strong>HAIR based on arterial and hepatobiliary phase provides a quantitative, reproducible and interpretable tool for DN/HCC differentiation.</p>","PeriodicalId":15906,"journal":{"name":"Journal of Hepatocellular Carcinoma","volume":"13 ","pages":"609066"},"PeriodicalIF":3.9,"publicationDate":"2026-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13179798/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147963851","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":"USP9X Promotes Hepatocellular Carcinoma Progression via Stabilization of HSP90AA1.","authors":"Hanlin Jiang, Lining Huang, Jiahao Chen, Zongying Jiang, Weiqiao Niu, Jianwu Wu, Zhiming Qiao, Yujia Pan, Xinwei Jiang","doi":"10.2147/JHC.S585217","DOIUrl":"10.2147/JHC.S585217","url":null,"abstract":"<p><strong>Background: </strong>Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality worldwide. Ubiquitin-specific proteases (USPs) modulate tumor progression by regulating substrate protein stability. However, the mechanisms of most DUBs in HCC remain poorly understood. This study aimed to investigate the role of USP9X in promoting HCC cell proliferation, survival, migration, and invasion.</p><p><strong>Methods: </strong>Transcriptomic and clinical data of LIHC patients were obtained from TCGA to assess USP9X expression, prognosis, and pathway enrichment. USP9X expression in HCC and adjacent tissues was examined by immunohistochemistry and Western blotting. Functional assays (CCK-8, colony formation, wound-healing, Transwell) were performed following USP9X knockdown or overexpression in Lm3 and Huh7 cells. The USP9X-HSP90AA1 interaction was evaluated by Co-IP and mass spectrometry, and deubiquitination assays elucidated the mechanism. In vitro and in vivo experiments determined the effects of USP9X-HSP90AA1 signaling on HCC growth and metastasis.</p><p><strong>Results: </strong>Bioinformatic analyses revealed that USP9X expression was significantly elevated in LIHC tissues and correlated with poor prognosis. Immunohistochemistry and Western blotting confirmed higher USP9X protein levels in tumor tissues. Knockdown of USP9X inhibited proliferation and migration of Lm3 and Huh7 cells, whereas USP9X overexpression enhanced these phenotypes. Co-IP demonstrated a direct interaction between USP9X and HSP90AA1, and deubiquitination assays showed that USP9X decreased HSP90AA1 ubiquitination and increased its stability. Both in vitro and in vivo data indicated that USP9X promotes HCC progression through stabilization of HSP90AA1.</p><p><strong>Conclusion: </strong>USP9X is a tumor-promoting factor that accelerates HCC progression by stabilizing HSP90AA1, highlighting USP9X as a potential therapeutic target for HCC.</p>","PeriodicalId":15906,"journal":{"name":"Journal of Hepatocellular Carcinoma","volume":"13 ","pages":"585217"},"PeriodicalIF":3.9,"publicationDate":"2026-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13180381/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147972912","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":"Stromal ACTA2 Counteracts TCDD-Induced Hepatocarcinogenesis via Suppression of the PI3K-AKT-mTOR Pathway.","authors":"Ruoyang He, Ziqing Yang, Wenge Zhang, Yuehao Ren, Shuzi Li, Simin Zhan, Chuntian Wang, Zhen Zhang","doi":"10.2147/JHC.S586916","DOIUrl":"10.2147/JHC.S586916","url":null,"abstract":"<p><strong>Purpose: </strong>2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a persistent environmental pollutant that promotes hepatocellular carcinoma (HCC) through non-genotoxic mechanisms. However, stromal regulatory factors that counteract its tumor-promoting effects remain poorly defined. This study aimed to elucidate the role of actin alpha-2 (ACTA2) in TCDD-associated hepatocarcinogenesis.</p><p><strong>Methods: </strong>An integrative strategy combining network toxicology, Mendelian randomization, multi-omics and single-cell analyses, molecular docking and molecular dynamics simulations, along with in vitro experiments, was employed to investigate the functional role of ACTA2.</p><p><strong>Results: </strong>ACTA2 was identified as a stromal-associated factor linked to reduced HCC risk and improved patient survival. Single-cell and multi-omics analyses revealed that ACTA2 is predominantly expressed in hepatic stellate cells and fibroblast-like populations, reflecting tumor microenvironment composition rather than tumor cell-intrinsic expression. Functional enrichment analyses indicated that ACTA2 is associated with extracellular matrix remodeling and PI3K-AKT signaling. Molecular simulations demonstrated stable binding of TCDD to ACTA2 (ΔG_bind ≈ -7.05 kcal/mol), suggesting potential structural perturbation. In vitro experiments showed that TCDD downregulated ACTA2 expression, promoted proliferation of LX-2 and cancer-associated fibroblasts (CAFs), and activated PI3K-AKT-mTOR signaling, whereas ACTA2 overexpression attenuated these effects.</p><p><strong>Conclusion: </strong>ACTA2 acts as a context-dependent stromal regulator that modulates PI3K-AKT-mTOR signaling in TCDD-induced hepatocarcinogenesis. These findings highlight the importance of stromal remodeling in environmental carcinogenesis and suggest ACTA2 as a potential biomarker and therapeutic target in dioxin-associated HCC.</p>","PeriodicalId":15906,"journal":{"name":"Journal of Hepatocellular Carcinoma","volume":"13 ","pages":"586916"},"PeriodicalIF":3.9,"publicationDate":"2026-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13175077/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147963903","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":"Dosimetric Impact and Correction of Lipiodol Deposition on Photon-Beam Radiotherapy for Hepatocellular Carcinoma Using a Novel Simulation Model.","authors":"Chenlei Guo, Mengyuan Li, Yirui Zhai, Wei Sun, Xiaowu Zhang, Dong Yan, Wei Zhang, Ying Cao, Zhen Wang, Kaixuan Zhang, Xin Feng, Shulian Wang, Yuan Tang, Ye-Xiong Li, Kuo Men, Bo Chen","doi":"10.2147/JHC.S593372","DOIUrl":"10.2147/JHC.S593372","url":null,"abstract":"<p><strong>Purpose: </strong>To evaluate the influence of Lipiodol area on radiotherapy dose distribution in the photon-beam treatment planning system (TPS) and develop a new simulation model of Lipiodol deposition in patients with hepatocellular carcinoma (HCC).</p><p><strong>Patients and materials: </strong>We developed a Lipiodol deposition simulation model (LDSM) using a Lipiodol-porcine liver mixture to simulate the Lipiodol area after transcatheter arterial chemoembolization (TACE). The dose calculated by the TPS (D_TPS) and the detected dose (D_DET) using 6 MV X-ray irradiation using different fractional doses (1-10 Gy/f) delivered by flattening-filter (FF) or flattening-filter-free (FFF) beams were compared. The computed tomography (CT) images of 60 patients with HCC who had undergone TACE were retrospectively reviewed and subjected to relative electron density (RED) correction and dosimetric evaluation. The dose deviation was evaluated across different TPS platforms and calculation algorithms.</p><p><strong>Results: </strong>In the Pinnacle³ TPS with the collapsed cone convolution algorithm, the LDSM revealed a dose underestimation due to Lipiodol area in the photon-beam TPS, with the dose deviation factor (δ) increasing with increasing Lipiodol concentration (p < 0.001). The effects of FF and FFF beams ranged from 0.3% to 4.3% and 0.5% to 5.7%, respectively, but dose deviation was not correlated with fractional dose. In patients' re-evaluated radiotherapy plans, the prescription dose coverage of gross tumor volume improved by a mean of 3.42% ± 0.92% (range, 2.00-4.99%). The 50% prescription dose coverage of normal liver increased by 0.72% ± 0.36% (range, 0-1.3%), and the maximum dose (D_MAX) to gastrointestinal tissue increased by 183.22 ± 138.80 cGy (range, 2.00-453.00 cGy). The shortest distance between the tumor and the gastrointestinal tissue was an independent predictor of gastrointestinal dosimetric deviation.</p><p><strong>Conclusion: </strong>After TACE, Lipiodol area has a clinically significant dosimetric effect leading to the TPS underestimating the gastrointestinal D_MAX delivered by the photon-beam. The dosimetric deviations should be corrected, especially in the TPS with the convolution algorithm.</p>","PeriodicalId":15906,"journal":{"name":"Journal of Hepatocellular Carcinoma","volume":"13 ","pages":"593372"},"PeriodicalIF":3.9,"publicationDate":"2026-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13172611/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147963939","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":"Liver Transplantation After Radiotherapy-Antiangiogenesis-Immune Checkpoint Blockade Combination Therapy in Hepatocellular Carcinoma with Major Portal Vein Tumor Thrombosis: A Propensity Score Matching Analysis.","authors":"Ying Zhao, Jiyong Song, Keren Li, Tao Li, Wei Li, Yanmei Yang, Xuan Tong, Ying Xiao, Guangxun Xu, Qian Lu, Guangxin Li, Gong Li, Jiahong Dong","doi":"10.2147/JHC.S570163","DOIUrl":"10.2147/JHC.S570163","url":null,"abstract":"<p><strong>Background: </strong>After downstaging, radiotherapy-antiangiogenesis-immune checkpoint blockade (RACIB) combination therapy has shown significant clinical efficacy in hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT), permitting liver transplantation (LT). This study evaluated LT patients' survival outcomes and prognostic factors after RACIB treatment.</p><p><strong>Patients and methods: </strong>This retrospective analysis comprised 28 HCC with major PVTT (Vp3/Vp4, portal invasion at the first portal branch or main portal branch according to Japanese Vp classification) patients who were downstaged with RACIB combination therapy between January 2018 and December 2022. 13 patients who achieved successful downstaging underwent LT (RACIB+LT group), while 15 patients who achieved downstaging but did not undergo LT (due to patient choice, lack of donor, or other clinical reasons) formed the non-LT control group (RACIB-only group). Kaplan-Meier analysis and the Log rank test were used for survival analysis. For comparative analysis, one-to-one paired cohorts were derived using propensity-score matching (PSM) analysis.</p><p><strong>Results: </strong>Over a median follow-up period of 32.1 months (range: 4.1-46.0 months), the median overall survival (OS) and disease-free survival (DFS) were 31.1 and 10.1 months in the LT following RACIB group, and 14.5 months and 7.6 months in the RACIB group, respectively. The LT following RACIB group exhibited significantly better 3-year OS (42% vs 0, p=0.041) and 3-year progression-free survival (15.4% vs 0, p=0.047) than those who only underwent RACIB. In the PSM analysis, the 2-year OS was also superior in the LT following RACIB group (45.7% vs 0, p=0.042). Kaplan-Meier analysis showed that long interval from radiotherapy (RT) to LT, alpha fetoprotein (AFP) levels dropped to normal, AFP was reduced by half and patients with major pathologic response had superior OS (p=0.014, 0.005, 0.019, and 0.023) and DFS (p=0.025, 0.013, 0.011, and 0.014) compared to patients without any of the parameters. In DFS multivariate analysis, the interval from RT to LT and AFP normalization before LT were independent prognostic factors. The RACIB regimen was well tolerated, with no grade ≥3 treatment-related adverse events observed.</p><p><strong>Conclusion: </strong>Selected HCC patients with major PVTT can be considered viable candidates for LT after downstaging using RACIB combination therapy, with identified prognostic parameters aiding decision-making.</p>","PeriodicalId":15906,"journal":{"name":"Journal of Hepatocellular Carcinoma","volume":"13 ","pages":"570163"},"PeriodicalIF":3.9,"publicationDate":"2026-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13165477/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147930365","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":"Metastatic Fibrolamellar Hepatocellular Carcinoma in a Young Adult: A Case Report and Narrative Review.","authors":"Roy El Darzi, Christopher Ashy, Ali Khrayzat, Sally Chahine, Ayman Tawil, Sally Temraz","doi":"10.2147/JHC.S597439","DOIUrl":"10.2147/JHC.S597439","url":null,"abstract":"<p><p>Fibrolamellar hepatocellular carcinoma (FLC) is a rare and distinct histologic subtype of hepatocellular carcinoma that typically arises in non-cirrhotic livers of adolescents and young adults without underlying viral hepatitis or chronic liver disease. Accounting for less than 1% of all primary liver cancers, FLC is characterized by unique clinical, radiologic, and molecular features, most notably the highly characteristic <i>DNAJB1-PRKACA</i> fusion. Due to its rarity and frequently nonspecific presentation, diagnosis is often delayed or misinterpreted as by benign hepatic lesions such as focal nodular hyperplasia or adenoma. This report presents a rare case of metastatic FLC in a young adult who initially presented with right upper quadrant pain, anemia, and preserved hepatic function. Imaging revealed a large hepatic mass with a central non-enhancing area suggestive of necrosis, and histopathologic evaluation aided in the diagnosis based on characteristic lamellar fibrosis, polygonal eosinophilic cells, and positive CK7 and HepPar-1 staining. Confirmatory molecular testing through <i>DNAJB1-PRKACA</i> fusion was not performed. Planned treatment with a combination regimen of nivolumab and neratinib was scheduled; however, the patient deteriorated rapidly, and systemic therapy could not be initiated before death. Through this case and accompanying review, we aim to highlight the diagnostic complexity, molecular underpinnings, and current therapeutic approaches of FLC. This case was notable for advanced peritoneal carcinomatosis at presentation, severe thrombocytosis, and the diagnostic and therapeutic challenges posed by metastatic fibrolamellar carcinoma without molecular confirmation. Taken together, this underscores the importance of early recognition, molecular testing, and coordinated clinical management in optimizing outcomes for this uncommon malignancy.</p>","PeriodicalId":15906,"journal":{"name":"Journal of Hepatocellular Carcinoma","volume":"13 ","pages":"597439"},"PeriodicalIF":3.9,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13157843/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147874418","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":"ADAM12 Stabilizes EIF3B to Promote Glycolysis and Tumor Progression in Hepatocellular Carcinoma.","authors":"Shengdong Wu, Yongfei Zhu, Yan Xia, Shengjun Wu, Caide Lu","doi":"10.2147/JHC.S560478","DOIUrl":"10.2147/JHC.S560478","url":null,"abstract":"<p><strong>Background: </strong>Hepatocellular carcinoma (HCC) is a highly aggressive malignancy with poor prognosis and limited therapeutic options. A disintegrin and metalloproteinase 12 (ADAM12) is aberrantly expressed in multiple cancers and has been implicated in tumor progression. However, its biological role and underlying mechanism in HCC remain unclear.</p><p><strong>Methods: </strong>Public HCC datasets and bioinformatics analyses were used to evaluate ADAM12 expression and its clinical significance. The effects of ADAM12 on HCC cell viability, colony formation, migration, invasion, and apoptosis were assessed in vitro, and its role in tumor growth was examined in a xenograft model. The underlying mechanism was investigated by immunoprecipitation-mass spectrometry, co-immunoprecipitation, cycloheximide chase, ubiquitination, and metabolic assays.</p><p><strong>Results: </strong>ADAM12 was significantly upregulated in HCC tissues and was associated with unfavorable overall survival. ADAM12 knockdown inhibited cell viability, colony formation, migration, and invasion, promoted apoptosis in vitro, and suppressed xenograft tumor growth in vivo without obvious body weight loss. Mechanistically, EIF3B was identified as an ADAM12-interacting protein. ADAM12 knockdown decreased EIF3B protein abundance without affecting its mRNA level, accelerated EIF3B degradation, and increased its ubiquitination, indicating that ADAM12 stabilizes EIF3B by limiting ubiquitin-proteasome-mediated degradation. Moreover, ADAM12 depletion reduced PKM2 and LDHA expression, decreased extracellular acidification rate, lactate production, and glucose uptake, and increased oxygen consumption rate, indicating a shift from glycolysis toward oxidative phosphorylation. These effects were largely rescued by EIF3B overexpression or PKM2 restoration.</p><p><strong>Conclusion: </strong>ADAM12 promotes glycolytic reprogramming and tumor progression in HCC by stabilizing EIF3B and regulating the EIF3B/PKM2 axis. The ADAM12-EIF3B pathway may therefore represent a potential therapeutic target in HCC.</p>","PeriodicalId":15906,"journal":{"name":"Journal of Hepatocellular Carcinoma","volume":"13 ","pages":"560478"},"PeriodicalIF":3.9,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13157870/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147874390","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}