Journal of Hepatocellular Carcinoma最新文献

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.].

Purpose: This study aimed to evaluate the impact of middle hepatic vein (MHV) resection during hemihepatectomy on short-term surgical outcomes and long-term prognosis in patients with hepatocellular carcinoma (HCC).

Patients and methods: Patients with HCC at Barcelona Clinic Liver Cancer (BCLC) stages 0-B who underwent hemihepatectomy between January 2016 and December 2022 were retrospectively screened. They were categorized into the MHV-preserved and MHV-resected groups. Intraoperative parameters, postoperative complications, liver function, overall survival (OS), and recurrence-free survival (RFS) were compared. Cox regression analyses were used to identified independent risk factors for OS and RFS.

Results: A total of 137 patients were included, of whom 107 (78.1%) had MHV preserved and 30 (21.9%) had MHV resected. Compared with MHV preservation, MHV resection was associated with a longer operative time (329.9 ± 108.0 vs 291.4 ± 88.9 min, P = 0.048), greater intraoperative blood loss (1025.0 [400.0-2075.0] vs 500.0 [300.0-800.0] mL, P = 0.002), and a higher need for intraoperative blood transfusion (43.3% vs 24.3%, P = 0.041). Postoperative serum ALT and AST levels on days 3 and 5 were significantly higher in the MHV-resected group (all P < 0.05). However, postoperative hospital stay, complication rates, and other liver function parameters (ALB, TBIL, DBIL, PT, INR) did not differ significantly between the two groups. No significant differences were found in OS or RFS (all P > 0.05).

Conclusion: MHV resection during hemihepatectomy increases operative time, blood loss, and postoperative liver enzyme levels, but does not significantly impact long-term survival in patients with HCC.

Gastropleural fistula (GPF) is an extremely rare complication after treatment for liver cancer. We report a case of a 54-year-old man with hepatitis B virus (HBV)-related liver cancer who developed a GPF after multiple sessions of transarterial chemoembolization (TACE) combined with immunotherapy and targeted therapy. During the third treatment, because of arterial remodeling and changes in tumor vascular supply, the embolization route was changed to the left inferior phrenic artery. After the procedure, the patient presented with abdominal pain, chest pain, and fever. Metagenomic next-generation sequencing (mNGS) of the pleural effusion identified Porphyromonas endodontalis, and Pneumocystis jirovecii was also detected in the sputum. Upper gastrointestinal endoscopy and water-soluble contrast radiography confirmed a gastric fundus perforation with a fistulous communication to the pleural cavity. After multidisciplinary evaluation, the patient underwent laparoscopic fistula repair and had a favorable postoperative recovery. This case highlights that, while the combination of TACE, immunotherapy, and targeted agents may provide synergistic antitumor benefits, it also carries a potential risk of serious gastric complications.

Background: Patients with hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT) have poor outcomes and limited treatment options. Clinical data specifically evaluating the effects of intensity-modulated proton therapy (IMPT) for this population remain scarce. We reported the outcomes of patients with HCC with PVTT treated with IMPT.

Material and methods: We retrospectively reviewed the data of 83 patients with nonmetastatic HCC with PVTT treated with IMPT between March 2019 and June 2023. Survival outcomes were analyzed with Kaplan-Meier analysis, and prognostic factors were identified via multivariable Cox regression. Treatment responses were assessed with the modified Response Evaluation Criteria in Solid Tumors. Toxicities, including liver dysfunction and gastrointestinal events, were documented.

Results: The median overall survival (OS) was 32.4 months, with 1- and 2-year OS rates of 82.6% and 61.0%, respectively. The 2-year local control rate was 88.8%, and the objective response rate was 91.5%. Complete response after IMPT was independently associated with improved OS and liver control, whereas an albumin-bilirubin (ALBI) grade of 2 predicted a greater risk of liver dysfunction. Grade 3 gastrointestinal toxicities occurred in 4.8% of patients, and radiation-induced liver disease occurred in 9.3%. IMPT facilitated curative-intent surgery in 8.4% of patients after treatment.

Conclusion: IMPT offers excellent local control and a favorable safety profile in patients with HCC and PVTT, with the potential to downstage tumors for curative interventions. These findings, though limited by the retrospective design and heterogeneity of systemic therapies, support the integration of IMPT into multidisciplinary treatment strategies and highlight the need for prospective studies to clarify its role alongside systemic therapy.

Background and objectives: The prognostic role of remnant cholesterol (RC) in hepatocellular carcinoma (HCC) remains unexplored. This study aimed to investigate the association between RC and overall survival (OS) in HCC patients after hepatectomy and to develop a robust prognostic model.

Materials and methods: 439 HCC patients who underwent curative hepatectomy were retrospectively analyzed. RC was calculated as total cholesterol minus (HDL-c + LDL-c). To specifically evaluate the potential nonlinear relationship, the association between RC and OS was assessed using restricted cubic splines (RCS) in addition to Cox regression and subgroup analyses. A machine learning approach employing nine algorithms was used to develop a prognostic model, with model interpretability achieved using SHapley Additive exPlanations (SHAP). An online predictive tool was subsequently deployed.

Results: A significant U-shaped relationship between RC and OS (P for non-linearity = 0.013) was identified, with the lowest risk observed at approximately 1.04 mmol/L. Both too low and too high RC levels were independent predictors of worse OS. Among the machine learning models, XGBoost demonstrated superior and consistent performance for predicting 1-, 3-, and 5-year OS. SHAP analysis confirmed RC as a key predictive feature, alongside TNM stage and tumor characteristics. An interactive web-based tool was successfully implemented for clinical use.

Conclusion: RC demonstrates a novel U-shaped association with HCC postoperative survival in an Asian HBV-endemic cohort, underscoring its role as a significant biomarker reflecting metabolic imbalance. The developed machine learning model, which integrates RC, provides accurate, interpretable, and individualized risk assessment, offering a valuable tool for clinical prognostication and potential guidance for personalized management strategies.