Journal of Hepatocellular Carcinoma最新文献

Objective: To develop a nomogram based on clinical characteristics for predicting post-transplant tumor recurrence in hepatocellular carcinoma (HCC) patients beyond the Milan criteria who received transarterial chemoembolization (TACE) bridging therapy.

Methods: A retrospective analysis included 73 such patients (29 conventional TACE [cTACE], 44 drug-eluting bead TACE [DEB-TACE]) who underwent liver transplantation at our institution between January 2013 and January 2020, with follow-up until January 2024 (mean: 33.2 ± 6.5 months). Clinical/pathological features were analyzed via univariate and multivariate Cox regression to identify recurrence-related factors, and a nomogram was constructed. Bootstrap validation (B=20) and receiver operating characteristic (ROC) curves (AUC) evaluated its performance.

Results: The 1-, 2-, 3-year cumulative recurrence rates were 17.8%, 23.3%, 24.7% (median recurrence time: 6 months). cTACE group rates (20.7%, 27.6%, 31.0%) were higher than DEB-TACE (15.9%, 20.5%, 20.5%; P=0.034). Independent risk factors: bridging therapy type (HR=2.402, P=0.034), microvascular invasion (HR=3.445, P=0.001), tumor necrosis rate (HR=26.664, P=0.002), pre-TACE AFP (HR=2.750, P=0.004). The nomogram's AUC for 1-, 2-, 3-year recurrence was 0.740, 0.764, 0.886, with good calibration via bootstrap.

Conclusion: A nomogram based on clinical characteristics accurately predicts post-transplant recurrence in HCC patients beyond the Milan criteria with TACE bridging therapy, providing guidance for optimizing donor allocation.

Purpose: This study aimed to develop and validate a noninvasive multiparametric magnetic resonance imaging (MRI) model integrating hepatobiliary-phase T1 mapping (T1HBP), tumor-to-liver R2-star ratio (TLRR2*), and clinical biomarkers to predict high Ki-67 expression (>30%) in patients with hepatocellular carcinoma (HCC).

Patients and methods: In this retrospective study, 60 patients with histopathologically confirmed HCC who underwent preoperative multiparametric MRI-including T1 mapping, proton density fat fraction (PDFF), and R2-star sequences-were enrolled. Based on immunohistochemical analysis, patients were classified into high (n=22) and low (n=38) Ki-67 expression groups. Clinical data and quantitative MRI parameters were compared between groups. Univariate and multivariate logistic regression analyses were conducted to identify independent predictors of high Ki-67 expression. The diagnostic performance of each parameter and the combined model was evaluated using receiver operating characteristic (ROC) curve analysis.

Results: Multivariate analysis identified serum total bilirubin (TBil; OR=1.109, p=0.032), T1HBP (OR=1.004, p=0.026), and TLRR2* (OR=5.428, p=0.034) as independent predictors of high Ki-67 expression. The multiparametric model incorporating TBil, T1HBP, and TLRR2* achieved superior predictive performance, with an area under the ROC curve (AUC) of 0.813 (95% CI: 0.704-0.923), significantly outperforming individual parameters (T1HBP AUC=0.682, TLRR2* AUC=0.671, TBil AUC=0.664; all p<0.05). Interobserver agreement for imaging measurements was excellent (ICC > 0.80).

Conclusion: The combined multiparametric MRI model incorporating T1HBP, TLRR2*and TBil provides a noninvasive approach for predicting high proliferative activity in HCC, representing a promising tool for preoperative risk stratification and personalized treatment planning.

Aim: To identify preoperative risk factors for prolonged length of hospital stay (LOS) in patients undergoing surgery for primary liver cancer and to develop a predictive nomogram.

Methods: We retrospectively analyzed 702 surgical patients from a single center (2020-2023). LOS was modeled using negative binomial regression based on preoperative factors to construct a nomogram. Model performance was evaluated via internal bootstrap validation (1000 resamples), calibration plots, and decision curve analysis. Prolonged LOS was defined as >17 days (75th percentile) for a secondary logistic regression analysis.

Results: Four independent preoperative factors predicted longer LOS: lower serum cholinesterase, higher fibrinogen, intrahepatic cholangiocarcinoma (vs hepatocellular carcinoma), and female sex (all p<0.05). The nomogram showed moderate discriminative ability (apparent AUC ~0.67) with good calibration. The mean absolute error for LOS prediction was ~4.6 days. For predicting prolonged LOS (>17 days), the logistic model achieved an AUC of ~0.67.

Conclusion: We developed an internally validated nomogram using routine preoperative data to estimate the risk of extended hospitalization after liver cancer surgery. This tool may help identify high-risk patients for targeted interventions, although its predictive accuracy is modest, and external validation is required before clinical application.

Purpose: To compare ultrasound-guided percutaneous puncture under local anesthesia (LA) versus open laparotomy under general anesthesia (GA) for establishing a rabbit VX2 liver tumor model, evaluating efficacy, safety, animal welfare, and tumor biology.

Methods: Twenty-eight rabbits were randomly assigned to Group A (ultrasound-guided percutaneous under LA, n = 14) or Group B (open surgery under GA, n = 14). Parameters compared included anesthesia and operation time, intraoperative blood loss, surgical trauma, postoperative complications, mortality, tumor implantation success rate, tumor volume, and tumor characteristics were evaluated via imaging and histopathological analysis.

Results: Compared to Group B, Group A demonstrated significantly shorter anesthesia preparation time (61.00 ± 6.70 s vs 632.60 ± 67.84 s, P < 0.0001) and operation time (4.99 ± 0.65 min vs 28.57 ± 5.35 min, P < 0.0001), alongside significantly reduced intraoperative blood loss (0.75 ± 0.26 mL vs 3.96 ± 0.77 mL, P < 0.0001). No significant differences were found in tumor implantation success rate (92.9% vs 85.7%) or tumor volume between the groups. However, Group A showed significantly lower rates of peritoneal seeding (7.1% vs 42.9%, P = 0.037) and abdominal wall invasion (0% vs 35.7%, P = 0.045). Group A also exhibited favorable trends in postoperative infection and mortality rates.

Conclusion: Ultrasound-guided percutaneous puncture under LA is a superior method for creating the VX2 liver model. It is faster, less invasive, reduces bleeding and tumor dissemination risk, maintains equivalent tumorigenicity, and better adheres to animal welfare principles.

Objective: To evaluate the efficacy and safety of TEM-TACE combined with HAIC and targeted/immunotherapy for the treatment of unresectable primary liver cancer, and to clarify the clinical application potential of this multimodal therapeutic regimen.

Methods: This study was a small-sample retrospective case series. The clinical data of 4 patients with unresectable primary liver cancer who underwent TEM-TACE combined with HAIC and targeted/immunotherapy in our hospital from April 2025 to July 2025 were retrospectively analyzed. Tumor response was evaluated according to the mRECIST criteria, and the occurrence of adverse reactions was assessed on the basis of the Clavien-Dindo classification system. All patients included in this study provided written informed consent for the publication of their clinical details.

Results: Among the 4 patients, 2 were diagnosed with HCC, and the other 2 were diagnosed with ICC. All 4 patients achieved a PR after treatment with TEM-TACE combined with HAIC and targeted/immunotherapy, with a mean tumor reduction of 42.3%. The ORR and DCR both reached 100%. Among these patients, 2 successfully achieved treatment conversion and underwent radical surgical resection, while the remaining 2 refused surgery for personal reasons. During the perioperative period, only Clavien-Dindo grade I-II complications (mainly abdominal pain and nausea) occurred in the 4 patients, which improved after symptomatic treatment, and no severe adverse reactions were observed.

Conclusion: The multimodal therapeutic regimen of TEM-TACE combined with HAIC and targeted/immunotherapy is safe and effective for unresectable primary liver cancer. In particular, compared with conventional embolic agents, temperature-sensitive embolic agents enable precise peripheral embolization and sustained drug release, thereby significantly reducing tumor volume and improving the rate of conversion to surgical resection. Moreover, this regimen provides a novel approach for the conversion therapy of unresectable ICC. It is suitable for patients with primary liver cancer who have a tumor diameter >10 cm, liver function of Child-Pugh class A/B, and no severe comorbidities. However, further studies with larger sample sizes are still required to verify its long-term efficacy.

Purpose: Real-world evidence concerning the triple-combination regimens of radiotherapy (RT), PD-1 inhibitors, and targeted therapy for unresectable hepatocellular carcinoma (uHCC) is limited. This study evaluated the efficacy and safety of this combination and identified predictors of survival.

Patients and methods: In this multicenter retrospective study, 122 consecutive patients with uHCC received RT combined with PD-1 inhibitors and targeted therapy were analyzed. Objective response rate (ORR), disease control rate (DCR), overall survival (OS), progression-free survival (PFS) and treatment-related adverse events (TRAEs) were calculated. Cox regression was used to identify independent prognostic factors. Subgroup analysis explored the association between immunotherapy cycles and overall survival across tumor response stratification.

Results: The cohort included 53 patients with extrahepatic metastases and 48 with macrovascular invasion. Patients received RT with a median dose of 45 Gy (range: 32.3-58.5 Gy). Median follow-up was 14.2 months. According to the modified response evaluation criteria in solid tumor (mRECIST), the ORR and DCR were 18.85% and 73.78%, respectively. The median OS was 19.0 months (95% CI: 17.8-23.4 months), and the median PFS was 7.2 months (95% CI: 5.5-10.9 months). TRAEs of any grade occurred in 93 patients (76.23%), with grade 3-4 TRAEs observed in 40 patients (32.79%). No treatment-related death was observed. Multivariate analysis identified elevated AFP and higher mALBI grade as independent risk factors for OS. Higher mALBI grade and neutrophil-to-lymphocyte ratio (NLR) predicted worse PFS. Exploratory analysis suggested extending immunotherapy duration may improve OS in patients with stable disease.

Conclusion: The triple-combination of RT, PD-1 inhibitors, and targeted therapy demonstrates promising survival benefits and a manageable toxicity profile for uHCC. Baseline AFP, liver function, NLR level are key determinants of survival, supporting the individualized application of this multimodal approach.

Purpose: Hepatocellular carcinoma (HCC) is a major cause of cancer deaths. This study developed a clinical prediction model to identify patients likely to respond to transcatheter arterial chemoembolization (TACE) combined with atezolizumab and bevacizumab (Atez/Bev), using Mendelian randomization (MR) to validate the therapeutic effect on HCC via PDCD1, CD274, and VEGFA.

Patients and methods: A retrospective analysis of 258 unresectable HCC patients administered TACE, with or without Atez/Bev therapy, was conducted. Propensity score matching (PSM) was employed to compare objective response rates (ORRs). A predictive model for response to TACE+Atez/Bev was developed using logistic regression and validated. MR was used to analyze the causal relationships between the PDCD1, CD274, VEGFA genes and Atez/Bev efficacy.

Results: After PSM, the TACE+Atez/Bev group demonstrated significantly higher ORR compared with the TACE group (73.8% vs 56.3%, p=0.031). Multivariate logistic regression identified hepatic vein invasion, albumin (ALB), and platelets (PLT) as key outcome factors, which were used to develop a nomogram with AUCs of 0.81 and 0.89 in the training and validation cohorts, respectively. Calibration curve analysis showed good agreement with actual outcomes, and decision curve analysis highlighted the nomogram's potential for patient selection. MR analyses provided genetic support for the therapeutic target, revealing a significant protective association between PDCD1 inhibition and HCC risk (inverse-variance weighted, DrugOR=0.713, 95% CI: 0.599-0.848, p<0.001). This finding substantiates the biological rationale for the PDCD1 inhibitor atezolizumab. No significant associations were found for CD274 or VEGFA.

Conclusion: We developed a predictive model for TACE+Atez/Bev therapy, enabling effective patient screening. MR validated PDCD1's role in HCC immunotherapy at the genetic level.

Purpose: Steatotic liver disease (SLD), linked to obesity and metabolic disorders, is a growing health burden. While implicated in hepatocarcinogenesis, its prognostic role in resectable hepatocellular carcinoma (HCC) is unclear, with conflicting reports and uncertain interaction with viral hepatitis. We aimed to evaluate the impact of concurrent SLD on recurrence-free (RFS) and overall survival (OS) in HCC, and to explore differences across etiologic subgroups.

Patients and methods: In this retrospective cohort study, we analyzed 2123 HCC patients who underwent curative hepatic resection between 2009 and 2023. Patients were stratified by histologically defined SLD (≥5% steatosis in non-tumorous liver). Primary outcomes were RFS and OS. Subgroup analyses were performed by HCC etiology.

Results: SLD was present in 52.2% of patients and associated with favorable metabolic and tumor profiles. While RFS did not differ between groups (P = 0.942), patients with SLD had significantly improved OS (P = 0.001). On multivariate analysis, SLD remained an independent protective factor for mortality (HR 0.76, P = 0.005). The survival benefit was most evident in chronic hepatitis B (CHB) patients (HR 0.71, P = 0.011), and SLD was associated with significantly lower risks of both liver-related mortality (P=0.006) and non-liver-related mortality (P=0.001).

Conclusion: Concurrent SLD was associated with improved overall survival after curative resection for HCC, particularly among patients with CHB. These findings suggest that SLD may represent a clinically relevant prognostic factor in resectable HCC; however, the observed association should be regarded as hypothesis-generating and requires prospective validation.

Objective: The Solute carrier family 25 member 3 (SLC25A3), a mitochondrial solute carrier protein, has been implicated in tumor progression. Nonetheless, the connection between SLC25A3 and hepatocellular carcinoma (HCC) remains ambiguous.

Methods: The expression, mutation, clinical relevance and immune cell infiltration of SLC25A3 in HCC were investigated via integrated bioinformatics analysis using TCGA data. Hub genes were identified by constructing a protein-protein interaction (PPI) network, and the prognostic risk model was established using univariate Cox and LASSO regression analyses. The potential biological functions of SLC25A3 in HCC were elucidated through GO and KEGG analysis using SLC25A3 co-expressed genes. SLC25A3 expression and promoter methylation status in HCC cells was validated by qRT-PCR and bisulfite sequencing PCR, and the biological function of SLC25A3 in HCC was verified through in vitro loss-of-function experiments.

Results: SLC25A3 was significantly upregulated in HCC, accompanied by hypomethylation of its promoter region. Elevated SLC25A3 expression was positively correlated with T stage, histologic grade, AFP level, vascular invasion, residual tumor, and unfavorable prognosis, and served as an independent prognostic factor. SLC25A3 expression was correlated with infiltration of multiple immune cell types. The top 10 SLC25A3 associated-hub genes (SNRPF, SNRPB, SNRPE, SNRPD1, SNRPG, EFTUD2, SNRNP200, SF3A3, SNRPA1, LSM2) were recognized. A four-gene prognostic signature derived from SLC25A3-related hub genes (SNRPB, EFTUD2, SF3A3, and SNRPA1) demonstrated favorable predictive performance. Functional enrichment analysis disclosed that SLC25A3 co-expressed genes were predominantly engaged in RNA splicing, ribosome biogenesis, chromosome segregation, cell cycle and DNA replication. Experimental validation further confirmed that SLC25A3 was remarkably raised in HCC cell lines, with its promoter region displaying a hypomethylated status, and silencing of SLC25A3 suppressed proliferation, migration, and invasion while promoting apoptosis in HCC cells.

Conclusion: SLC25A3, a member of the mitochondrial solute carrier family, may function as a novel prognostic biomarker and therapeutic target for HCC.