Journal of Hepatocellular Carcinoma最新文献

Background: Microvascular invasion (MVI) serves as a well-established prognostic factor for tumor recurrence and reduced survival following curative hepatectomy in hepatocellular carcinoma (HCC). This investigation aims to assess the therapeutic value of postoperative adjuvant transcatheter arterial chemoembolization (PA-TACE) in HCC patients with MVI and delineate the optimal patient subpopulations for this intervention.

Methods: This retrospective cohort study analyzed patients with MVI in HCC patients who received curative resection from September 2013 to June 2019. After balancing baseline differences between the PA-TACE group and the non-TACE control group using propensity score matching (PSM), the differences in recurrence-free survival (RFS) and overall survival (OS) between the two groups were compared. A multivariate Cox proportional hazards regression model was used to identify independent prognostic factors.

Results: Among 440 evaluable patients, PA-TACE demonstrated statistically significant improvements in both RFS and OS compared to non-TACE management, with consistent results observed in both the entire and propensity score-matched cohorts. Multivariate analysis established PA-TACE as an independent protective predictor for both RFS and OS. Subgroup analyses revealed pronounced clinical benefits in patients exceeding Milan criteria and those presenting with high-risk features including serum AFP ≥400 ng/mL, tumor size ≥5 cm, Edmondson-Steiner grade III/IV differentiation, M2-type MVI, or major hepatectomy. Notably, no survival advantage was observed in patients within Milan criteria or BCLC-A/B stages.

Conclusion: PA-TACE provides substantial survival enhancement in HCC patients with MVI exceeding Milan criteria or with high-risk features, but offers limited benefit for Milan-eligible cases. Patient selection based on tumor biology is critical for optimizing adjuvant therapy.

Purpose: This study aimed to identify independent risk factors for hepatocellular carcinoma (HCC) in patients initially diagnosed with Budd-Chiari syndrome (BCS) and develop a nomogram for HCC risk assessment in these patients.

Patients and methods: Retrospective analysis was conducted on clinical data from 631 newly diagnosed BCS patients (BCS group) and 50 BCS patients complicated with HCC (HCC group) admitted to the Interventional Radiology Department of the Affiliated Hospital of Xuzhou Medical University (Xuzhou, China) between October 2014 and October 2021. General data, clinical symptoms/signs, laboratory tests, imaging features, Child-Pugh classification, and Model for End-Stage Liver Disease score were analyzed. Univariate logistic regression screened risk factors (P<0.05 for multivariate inclusion), and independent risk factors were selected via backward selection (Akaike Information Criterion) to build the nomogram, validated by bootstrap method. Receiver operating characteristic (ROC) curve, calibration curve, decision curve analysis (DCA), and clinical impact curve evaluated the model.

Results: Independent risk factors in the final model were disease duration [odds ratio (OR)=1.19, 95% CI=1.11-1.28], portal vein diameter (OR=140.29, 95% CI=31.63-622.22), and intrahepatic nodule formation (OR=5.03, 95% CI=2.42-10.44). Bootstrap validation showed the model's ROC area under the curve (AUC)=0.862 (95% CI=0.798-0.926), with cross-validation AUC=0.858 (95% CI=0.663-1.000, good discrimination). Calibration curves (model and internal validation) aligned with ideal status. DCA showed the nomogram had higher net benefit than extreme curves at 2-83% threshold probability. Clinical impact curve indicated threshold probability >60% identified HCC high-risk groups consistent with actual HCC occurrence.

Conclusion: The independent risk factors for HCC in patients initially diagnosed with BCS were disease duration, portal vein diameter and intrahepatic nodule formation. The developed nomogram model exhibited good discrimination, accuracy and clinical applicability for the prediction of HCC risk in patients with BCS. This study, for the first time, established a nomogram for predicting the risk of HCC in patients with BCS in a single-center cohort in China, which can provide a new tool for early screening.

Background: BRAP, a BRCA1-binding protein, exhibits elevated expression across multiple cancers and correlates with poor prognosis in hepatocellular carcinoma (HCC). However, its precise mechanistic roles in HCC tumorigenesis and immune landscape remodeling remain undefined.

Methods: BRAP expression levels and its diagnostic/prognostic value in HCC were analyzed using clinical HCC tissues and public datasets (TCGA and ICGC). CCK-8, colony formation, and EdU assays were employed to evaluate BRAP's impact on HCC cell proliferation; these findings were further validated in vivo using CDX models. RNA-seq and TCGA data analyses were performed to identify BRAP-mediated cellular biological functions and potential underlying mechanisms, with further confirmed via flow cytometry and Western blotting. scRNA-seq data from the GEO and TCGA were used to assess correlations between BRAP expression and immune cell infiltration, as well as immune checkpoint genes (ICGs) expression in HCC. mfIHC, qRT‒PCR, and macrophage-tumor co-cultivation experiments were conducted to validate BRAP's regulatory effects on immunosuppressive cell components in HCC.

Results: BRAP expression is significantly upregulated in HCC tissues and correlates with advanced pathological grades and poor patient prognosis. BRAP knockdown markedly reduced HCC cell proliferation both in vitro and in vivo; this anti-proliferative effect was achieved by inducing cell cycle arrest via suppression of the RAF/MEK/ERK signaling pathway. HCC cells with high BRAP expression exhibited increased infiltration of immunosuppressive cells, upregulated ICGs expression, and promoted M2 macrophage polarization.

Conclusion: BRAP drives HCC progression by promoting proliferation via RAF/MEK/ERK and shaping an immunosuppressive microenvironment. We identify BRAP as a novel prognostic biomarker and promising immunotherapeutic target in HCC.

Background: Patients with hepatocellular carcinoma (HCC) and microvascular invasion (MVI) face high post-resection relapse risk. Whether adjuvant PD-1 alone or with anti-vascular endothelial growth factor (anti-VEGF) improves outcomes remains uncertain.

Methods: Between 1 January 2022 and 1 January 2023, 170 consecutive patients from three Chinese centers were retrospectively reviewed. After resection, 69 received observation, 46 received intravenous sintilimab, and 55 received sintilimab plus either oral lenvatinib or intravenous bevacizumab biosimilar. Recurrence-free survival (RFS) was analyzed with Kaplan-Meier estimates and Cox models.

Results: Median follow-up was 24.7 months. Recurrence or death occurred in 42/69 (60.9%) observation patients, 19/46 (41.3%) sintilimab patients, and 23/55 (41.8%) combination patients. Median RFS was 16.1 months after observation, versus 29.5 months with sintilimab (hazard ratio=0.55, 95% confidence interval=0.32-0.95; P = 0.033) and 30.5 months with sintilimab plus anti-VEGF therapy (hazard ratio=0.55, 95% confidence interval=0.33-0.92; P = 0.023). One- and two-year RFS rates were 58.0% and 40.0% for observation, 73.9% and 66.6% for sintilimab, and 81.8% and 63.0% for combination therapy. Overall survival analysis is immature, median overall survival has not been reached in any group.

Conclusion: Adjuvant sintilimab, with or without anti-VEGF therapy, significantly prolonged RFS compared with surgery alone in patients with MVI-positive HCC. The magnitude of benefit was comparable between monotherapy and combination therapy, indicating that routine addition of anti-VEGF therapy may not be necessary for all patients.

Purpose: The optimal therapeutic strategy of hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT) is debated. This study aimed to compare the survival outcomes of liver resection (LR) versus targeted therapy plus programmed death-1 (PD-1) inhibitors in HCC patients with PVTT.

Patients and methods: The data of 53 patients with HCC and type I-II PVTT was retrospectively assessed. Among them, 23 underwent LR, and 30 received targeted therapy plus PD-1 inhibitors (TT + PD-1). The baseline characteristics, overall survival (OS) and progression-free survival (PFS) of the two groups were compared. Univariable and multivariable Cox regression analysis were performed to identify independent prognostic factors of OS and PFS.

Results: There were no significant differences in baseline characteristics between the LR and TT + PD-1 groups. The LR group showed a significantly superior median OS (27.3 vs 15.3 months; P < 0.001) and PFS (13.8 vs 7.5 months; P = 0.008) compared to the TT + PD-1 group. Multivariable Cox regression analysis identified LR was independently associated with a better OS and PFS.

Conclusion: LR may represent an effective therapeutic option for HCC patients with type I-II PVTT.

Background: Hepatocellular carcinoma (HCC) remains a highly challenging malignancy to treat with a dismal prognosis. The immunosuppressive tumor microenvironment (TIME), particularly regulatory T cells (Tregs), is a key driver of treatment resistance. This study aimed to investigate the anti-tumor efficacy and underlying mechanism of taurine-modified gossypol (GT)-a novel conjugate derived from two natural products (taurine and gossypol) with potential synergistic activity.

Methods: The anti-proliferative (CCK-8 assay), pro-apoptotic (Annexin V/PI staining) and cell cycle-regulatory (PI staining) effects of GT were evaluated in HepG2 cells and patient-derived HCC organoids. scRNA-seq and multiparametric flow cytometry were used to analyze alterations in the TIME. Molecular docking and surface plasmon resonance (SPR) were performed to validate the binding affinity (KD) between GT and FASN. Western blotting assessed PI3K/AKT and lipid metabolism pathways.

Results: GT dose-dependently inhibited HCC proliferation, induced apoptosis and caused G1 arrest, with concomitant PI3K/AKT pathway suppression. scRNA-seq revealed a selective reduction in Treg proportion following GT treatment. Mechanistically, GT bound to FASN with high affinity, inhibiting its activity and disrupting lipid metabolism in Tregs, thereby reprogramming Treg differentiation and function. In HCC patients, a clinically significant link was observed between high levels of FASN expression and reduced survival, based on an analysis of TCGA data.

Conclusion: GT exerts synergistic anti-HCC effects through a dual mechanism: directly suppressing tumor proliferation by inactivating the PI3K/AKT pathway, and remodeling the TIME by targeting FASN-dependent lipid metabolism in Tregs. These findings highlight the potential of GT as a novel multitargeted agent for HCC treatment.

Purpose: To evaluate the short-term clinical efficacy, side effects and risk factors affecting the clinical effectiveness of the combination of lipidol and epirubicin-loaded drug-eluting bead transarterial chemoembolization (DEB-TACE) in the treatment of hepatocellular carcinoma (HCC).

Methods: A total of 120 patients with HCC who underwent DEB-TACE plus lipiodol treatment from December 2017 to August 2020 were enrolled. Short-term local tumor response was evaluated using mRECIST. Postoperative complications and liver function disorders were analyzed on the basis of clinical parameters.

Results: The median overall survival (OS) was 31.44 months (95% CI: 27.24-35.46 months). According to mRISIST, the disease control rate is 75.8%. The objective response rate was 22.5%. Multivariate analysis showed that tumor size and conversion therapy were the two independent prognostic factors correlated with OS. Postoperatively, liver function showed transient changes and no grade 4 adverse events were observed. Most of the postoperative complications were characterized by post-embolism syndrome.

Conclusion: The combination of lipiodol and DEB-TACE offers effective local control and safety for patients with HCC. Lipiodol used in the DEB-TACE procedure provides several additional benefits for drug-eluting beads embolization. The synergistic effect of these two methods enhances therapeutic efficacy through dual antitumor mechanisms.

Background: Hepatocellular carcinoma (HCC) is a aggressive cancer associated with high morbidity and mortality globally. Reliable biomarkers are urgently needed to enhance diagnostic accuracy and survival outcomes in patients with HCC. This study aimed to evaluate the prognostic value of cleavage stimulation factor subunit 1 (CSTF1) in HCC.

Methods: CSTF1 expression in different cancer types, including HCC, was analyzed using data from The Cancer Genome Atlas. Immunohistochemistry was performed to assess CSTF1 expression in clinical samples. Logistic regression analyses were used to evaluate associations between CSTF1 expression and the clinical characteristics of patients with HCC. Furthermore, Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, and gene set enrichment analysis (GSEA) were performed to identify signaling pathways and biological functions linked to differentially expressed genes. The prognostic significance of CSTF1 in HCC was assessed via the Kaplan-Meier method and Cox univariate and multivariate analyses. Immune cell infiltration was investigated through single-sample GSEA and the CIBERSORT algorithm. Three nomograms were constructed to predict overall survival (OS), disease-specific survival (DSS), and progression free interval (PFI) rates at 1, 3, and 5 years after diagnosis.

Results: CSTF1 expression was elevated in HCC cases and closely correlated with multiple clinical features. Elevated CSTF1 expression was strongly associated with various cancer-related pathways and the immune microenvironment. The Kaplan-Meier analysis revealed that elevated CSTF1 expression predicts poorer prognostic outcomes in individuals with HCC. CSTF1 hypermethylation was also related to poor patient outcomes. The constructed nomograms for OS, DSS, and PFI achieved concordance indices of 0.631, 0.719 and 0.787, respectively.

Conclusion: These findings suggest that CSTF1 can serve as a novel prognostic biomarker for HCC. Evidence from immunohistochemistry and bioinformatics analyses supports CSTF1 as a prognostic indicator and a potential therapeutic target. This discovery could enhance diagnostic precision and improve survival outcomes for patients with HCC.

Purpose: Fibroblast growth factor 21 (FGF21) is a hormone synthesized and released by liver cells. Deficiency in FGF21 has been shown to be associated with steatosis, inflammation, fibrosis, and increased risk of hepatocellular carcinoma (HCC) development. Moreover, recent evidence suggests that elevated FGF21 levels may paradoxically correlate with worse outcomes in HCC. We aimed to evaluate the association between serum FGF21 levels, clinicopathological parameters, and overall survival (OS) in HCC patients.

Patients and methods: From 2001 to 2014, newly diagnosed HCC patients were recruited as part of an IRB-approved protocol. Blood samples were prospectively collected and a CLIA-certified lab measured serum FGF21 concentrations. Using FGF21 median as a cutoff point, all patients were categorized into subjects with low and high levels. The primary endpoint was OS.

Results: A total of 767 HCC patients were analyzed. Mean age was 65 years, and 74% were male. Median FGF21 value was 0.41 ng/mL. Our data showed that patients with advanced HCC including those with multinodular tumors, vascular invasion, distant metastasis, a higher Child-Pugh score, CLIP, BCLC, TNM, and ECOG stage had significantly increased FGF21 serum levels (p < 0.05 for all parameters). OS was significantly shorter in patients with high FGF21 compared to those with low FGF21 (24 months OS 28% vs 43%; p < 0.001). On multivariate analysis, high FGF21 was significantly associated with worse OS (HR: 1.422; 95% CI: 1.180-1.714; p < 0.001).

Conclusion: Elevated circulating FGF21 levels correlate with advanced clinicopathologic features and poor OS in HCC patients. Because elevated FGF21 during liver stress may indicate significant metabolic disruption, our data provides strong evidence that FGF21 may represent a valuable prognostic and potentially therapeutic biomarker in HCC. Future independent studies are required to validate our results.

[This corrects the article DOI: 10.2147/JHC.S521878.].