Journal of Hepatocellular Carcinoma最新文献

Background: Unresectable hepatocellular carcinoma (uHCC) remains a major clinical challenge with limited effective therapeutic options. Triple therapy combining interventional treatments, donafenib, and anti-PD-1 monoclonal antibodies has shown promise in recent studies, but real-world data remain limited.

Objective: To evaluate the real-world efficacy and safety of triple therapy with interventional treatment, donafenib, and anti-PD-1 monoclonal antibodies in patients with uHCC.

Methods: This retrospective study included 89 patients with uHCC who received donafenib, anti-PD-1 monoclonal antibodies (tislelizumab or sintilimab), and interventional therapies (TACE and/or HAIC) between March 2022 and December 2023. Outcomes included objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and safety. Efficacy was assessed using modified RECIST (mRECIST) criteria; prognostic factors were analyzed using Cox regression models.

Results: Among 89 patients, the ORR was 75.3% and the disease control rate was 100%. The median PFS was 18.5 months (95% CI: 15.0-NA); median OS was not reached after a median follow-up of 13.7 months. PFS rates at 6, 12, and 18 months were 87.6%, 72.4%, and 52.7%, and OS rates were 93.3%, 81.6%, and 72.4%, respectively. Conversion surgery was achieved in 15.7% of patients. Subgroup analysis indicated that ECOG PS 1, extrahepatic metastases, and high baseline AFP were associated with worse survival outcomes, while interventional modality did not significantly affect prognosis. Multivariate analysis confirmed ECOG PS 1 and extrahepatic metastases as independent predictors of shorter PFS, and ECOG PS 1 and elevated AFP as independent predictors of worse OS. Grade ≥3 treatment-related adverse events occurred in 30.3% of patients; no treatment-related deaths were reported.

Conclusion: The combination of interventional therapies, donafenib, and anti-PD-1 monoclonal antibodies demonstrated promising efficacy and manageable safety in uHCC, warranting further validation in prospective trials.

Background: The tumor immune microenvironment (TME) plays a key role in the development of hepatocellular carcinoma (HCC). As the important components of TME, interleukin-2 (IL-2) mediates immune responses by specifically binding to the interleukin-2 receptor (IL-2R). This study aimed to explore the role of IL-2R in HCC development and provided possible clinical implications in HCC prognosis and treatment.

Methods: The IL-2R genetic data were acquired from publicly available TCGA and CCLE databases. Data processing and analysis, including construction of the prognostic model and evaluation of immune status in HCC, were performed on Xiantao platform by using statistical methods including the Wilcoxon test, Cox regression analysis, correlation analysis. GEPIA2 was used to explore the relationship between IL-2R genes expression and clinical stages, while genetic variations in IL-2R subunits in HCC were determined using cBioPortal. The IL-2Rα co-expression gene analysis was conducted on the LinkedOmics database. Enzyme-linked immunosorbent assay (ELISA), colorimetric method, and flow cytometric method were used to analyze peripheral blood samples from patients with HCC.

Results: A prognostic risk model was established by incorporating IL-2Rα, IL-2Rβ, and IL-2Rγ expression. The infiltration levels of B cell memory, T cell regulatory cells (Tregs), and immune checkpoints (PDCD1, CTLA4, CD274 and TIGIT) were significantly elevated in high-risk group of the risk model. Additionally, sIL-2Rα levels were positively correlated with tumor-specific growth factor (TSGF) and Tregs in the peripheral blood of HCC patients.

Conclusion: The prognostic risk model based on IL-2R subunits may play a role in the regulation of immune function within the HCC tumor microenvironment. Besides, IL-2Rα may act as a more important role in HCC development among the three IL-2R subunits. Further research will be needed to verify these initial findings. Overall, these results may provide important insights in clinical prognosis and therapeutic strategies for HCC.

Background: Hepatocellular carcinoma (HCC) is a prevalent lethal cancer that remains challenging to treat. Therefore, investigation of novel targets and therapeutic strategies is essential. The role of ZBED4 in cancer remains unclear.

Methods: Data were sourced from The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), International Cancer Genome Consortium (ICGC), and Genomics of Drug Sensitivity in Cancer (GDSC) databases. Various web platforms and R software, have been utilized. Multiplex immunofluorescence was performed on a human HCC tissue microarray.

Results: High ZBED4 expression correlates with poor prognosis and immune cell infiltration in multiple cancers. ZBED4 is potentially involved in the regulation of the tumor environment by T cells, with a focus on CD8⁺ T cells. In HCC, tissues with elevated ZBED4 expression exhibit a higher prevalence of Tregs and neutrophils, whereas those with reduced ZBED4 expression show an increased abundance of CD8⁺ T cells, activated CD4⁺ T cells, gamma/delta T cells, and activated natural killer (NK) cells. Elevated ZBED4 expression in HCC patients is associated with a reduced response to immune checkpoint blockade but an improved response to chemotherapy and most targeted therapies. A multi-gene prognostic signature has been developed and confirmed across various HCC cohorts. Multiplex immunofluorescence study demonstrated that ZBED4 was linked to poor prognosis and negatively correlated with CD8⁺ T cell infiltration.

Conclusion: Our research elucidates the role of ZBED4, its strong link to immune infiltration, and its potential as a prognostic and therapeutic biomarker for HCC.

Purpose: To establish a patient charter that articulates the principles of quality care for individuals living with hepatocellular carcinoma (HCC), aiming to improve patient outcomes and survival rates globally.

Methods: A multidisciplinary group comprising healthcare professionals, patient advocacy representatives, and policymakers convened to identify the critical areas of unmet need in HCC care. The group shared patient experiences, barriers, and insights - particularly with input from Patient Advocacy Groups (PAGs) - to better understand the challenges faced by patients. They reviewed existing literature, current care practices, and patient experiences to formulate a patient charter that outlines the principles of quality care for HCC.

Results: The patient charter identifies the seven principles of quality care that people with HCC or at risk of developing HCC should expect to receive in order to benefit from improved outcomes and increased survival. These principles address the need for policy prioritization, early diagnosis, multidisciplinary care, personalized treatment, shared decision-making, stigma-free access to services and increased research funding.

Conclusion: The patient charter serves as a call to action for stakeholders to unite in enhancing the care and treatment of HCC, with the ultimate goal of improving health outcomes for patients.

Introduction: Large language models (LLMs) are increasingly used in healthcare, yet their reliability in specialized clinical fields remains uncertain. Liver cancer, as a complex and high-burden disease, poses unique challenges for AI-based tools. This study aimed to evaluate the comprehensibility and clinical applicability of five mainstream LLMs in addressing liver cancer-related clinical questions.

Methods: We developed 90 standardized questions covering multiple aspects of liver cancer management. Five LLMs-GPT-4, Gemini, Copilot, Kimi, and Ernie Bot-were evaluated in a blinded fashion by three independent hepatobiliary experts. Responses were scored using predefined criteria for comprehensibility and clinical applicability. Overall group comparisons were conducted using the Fisher-Freeman-Halton test (for categorical data) and the Kruskal-Wallis test (for ordinal scores), followed by Dunn's post-hoc test or Fisher's exact test with Bonferroni correction. Inter-rater reliability was assessed using Fleiss' kappa.

Results: Kimi and GPT-4 achieved the highest proportions of fully applicable responses (68% and 62%, respectively), while Ernie Bot and Copilot showed the lowest. Comprehensibility was generally high, with Kimi and Ernie Bot scoring over 98%. However, none of the LLMs consistently provided guideline-concordant answers to all questions. Performance on professional-level questions was significantly lower than on common-sense ones, highlighting deficiencies in complex clinical reasoning.

Conclusion: LLMs demonstrate varied performance in liver cancer-related queries. While GPT-4 and Kimi show promise in clinical applicability, limitations in accuracy and consistency-particularly for complex medical decisions-underscore the need for domain-specific optimization before clinical integration.

Trial registration: Not applicable.

Objective: This retrospective study was conducted to evaluate the effectiveness and safety of a new combination therapy of the multi-level comprehensive collateral artery embolism (CAE) sequential hepatic arterial infusion chemotherapy (HAIC), tyrosine kinase inhibitors (TKI) and immune checkpoint inhibitors (ICI) for unresectable huge hepatocellular carcinoma (>10cm) patients.

Methods: A propensity score-matching (PSM) cohort study was conducted. The initial tumor response, treatment-related adverse events, and survival outcomes were compared. The Forestplot package was used to visualize and interpret forest plots of overall survival subgroup analyses. Univariate and multivariate analyses were conducted to explore the risk factors of overall survival.

Results: Thirty-one pairs of patients were evaluated after PSM. There were statistically significant differences in the initial tumor response and objective response rate (ORR) between the two groups (74.2% vs 48.4%, P=0.037). Compared with the "HAIC" group, the incidence of abdominal pain was higher in the "CAE+HAIC" group (71.0% vs 41.9%, P=0.021). The OS and progression-free survival (PFS) of the "CAE+HAIC" group were longer than those of the "HAIC" group (OS: HR=0.439, 95% CI: 0.199-0.970, P=0.042; PFS: HR=0.475; 95% CI: 0.252-0.895; P=0.021). The CAE (HR=0.403, 95% CI: 0.213-0.762; P=0.005), prealbumin levels <170 mg/L (HR=2.195, 95% CI: 1.226-3.929; P=0.008), and lactic dehydrogenase levels >245 U/L (HR=2.136, 95% CI: 1.215-3.757; P=0.008) were independent risk factors of OS.

Conclusions: The multi-level comprehensive CAE sequential HAIC, combined with TKI and ICI, can improve tumor response and prolong survival time in unresectable huge HCC patients while remaining safe and tolerable.

Objective: This study aimed to identify independent predictors of early recurrence (ER) and to establish a clinically applicable, individualized nomogram for patients with solitary hepatocellular carcinoma (HCC) who underwent postoperative adjuvant transarterial chemoembolization (PA-TACE).

Methods: A total of 165 patients with solitary HCC treated with PA-TACE between January 2018 and December 2022 were retrospectively analyzed. Among these patients, 71 experienced ER, while 94 remained recurrence-free for over 24 months. Independent prognostic variables were identified through univariate and multivariate Cox regression analyses. These factors were integrated into a nomogram model, and its performance was evaluated using internal validation and calibration curves.

Results: Multivariate analysis revealed that AFP-L3% >10% (p = 0.009), presence of satellite lesions (p = 0.026), GLR >20 (p = 0.020), microvascular invasion (MVI) (p = 0.008), and Ki-67 expression >50% (p < 0.001) were independently associated with ER. These five variables were used to establish the nomogram, which had a C-index of 0.763 (95% CI: 0.736-0.870).

Conclusion: A nomogram incorporating AFP-L3, satellite lesions, GLR, MVI, and Ki-67 for predicting ER in patients with solitary HCC following PA-TACE was developed and validated. This model exhibits high predictive accuracy and provides a valuable tool for identifying patients who may benefit from PA-TACE.

Purpose: The aim of this study was to evaluate the potential of partial transcatheter arterial embolization (pTAE)-hepatic artery infusion chemotherapy (HAIC) in combination with tyrosine kinase inhibitors (TKIs) and anti-PD-1 antibodies for downstaging and subsequent resection in patients with initially unresectable hepatocellular carcinoma (HCC).

Methods: Patients with unresectable HCC who underwent initial treatment with a combination of pTAE, HAIC, TKIs, and an anti-PD-1 antibody were studied. The tumour response and potential for resection were assessed through imaging every month (±1 week) using RECIST v1.1.

Results: Among 17 patients (27.4%) who achieved R0 resection, the median time from quadruple therapy initiation to surgery was 89 days (range: 69-255). The cohort comprised 13 males and 4 females, with a median age of 51 years (range: 18-70). Twelve patients had BCLC stage C disease, including 11 with major vascular invasion (Vp2, Vp3, Vv2, Vv3, Vv1) and 3 with concurrent portal and hepatic venous invasion (Vp2/Vv2, Vp3/Vv2, Vp3/Vv3). Five patients had BCLC stage B HCC. The median diameter of the largest liver nodule was 11.5 cm (range: 3.9-18.8), with 10 patients presenting multiple lesions. Preoperatively, 17 patients underwent 43 cycles of pTAE-HAIC (median: 2, range: 1-5). Based on RECIST v1.1, 13 patients achieved partial response (PR), and 4 had stable disease (SD). With a median follow-up of 17.8 months (range: 12.2-38.3), the 12-month overall survival post-hepatectomy was 100%, and the median progression-free survival (PFS) was 14.5 months (range: 1.5-31.8). Tumor recurrence within 12 months occurred in 5 patients, with 4 achieving disease control after additional treatment.

Conclusion: Quadruple therapy, consisting of pTAE-HAIC combined with TKIs and anti-PD-1 antibodies, represents a feasible conversion strategy for patients with unresectable HCC to achieve successful resection and potential long-term survival.

Background: For hepatocellular carcinoma (HCC), adjuvant transarterial chemoembolization (TACE) shows an advantageous response and prognosis in recurrent patients after resection. In consideration of similar pathogenesis and clinicopathological characteristics, studies should be conducted to ascertain whether hepatitis B virus (HBV)-associated intrahepatic cholangiocarcinoma (ICC) can be successfully treated by the methods used to treat HCC. The role of adjuvant TACE following liver resection for HBV-associated ICC remains controversial. This study aims to evaluate the efficacy of adjuvant TACE on recurrence and survival after liver resection, both before and after propensity score weighting (PSW) analysis.

Materials and methods: A total of 356 patients were categorized into two groups: i) 77 patients who received adjuvant TACE, and ii) 279 patients who underwent R0 resection alone. Staging was conducted according to the 8th edition of the American Joint Committee on Cancer (AJCC) Tumor-Node-Metastasis (TNM) staging system. Univariate and multivariate analyses were utilized to assess independent prognostic factors. Recurrence-free survival (RFS) and overall survival (OS) rates were compared using the Kaplan-Meier method.

Results: Among the 356 enrolled patients, 77 received adjuvant TACE. The median follow-up period was 45.3 months. Adjuvant TACE did not significantly affect OS (P=0.629) before or after PSW. Subgroup analyses indicated that TACE was not associated with OS across different TNM stages. After propensity score weighting, Cox regression model indicated significantly increased recurrence risk with TACE (HR=1.53, 95% CI: 1.02-2.28; P=0.0071). Stage-specific risks were visually summarized in Supplementary Figure 1. Additionally, TACE did not significantly impact RFS in TNM stage I (P=0.1720) and stage II (P=0.7905) subgroups. Conversely, TACE was positively associated with increased recurrence risk in TNM stage III (P=0.0014) and stage IV (P=0.0051) patients.

Conclusion: These findings suggest that adjuvant TACE following radical surgery does not prolong OS for patients with HBV-associated ICC. Furthermore, adjuvant TACE was associated with increased recurrence risk in TNM Stage III and IV subgroups, though this observation requires further validation due to sample size limitations in advanced stages.

Objective: This study aimed to compare the efficacy and safety of transarterial chemoembolization followed by radiofrequency ablation (cTACE-RFA) versus RFA alone in patients with early-stage hepatocellular carcinoma (HCC) within the Milan criteria.

Methods: A retrospective analysis included 343 patients with Milan criteria-compliant HCC. After 1:1 propensity score matching (PSM), 93 patients underwent cTACE-RFA, and 93 received RFA alone. Primary endpoints were overall survival (OS) and local progression-free survival (LPFS).

Results: The TACE-RFA group demonstrated significantly superior 1-, 3-, and 5-year LPFS rates (84.9%, 58.1%, 36.6%) compared to the RFA group (75.3%, 44.1%, 16.1%; HR=0.54, 95% CI: 0.37-0.79, P=0.001). However, no significant 1-, 3-, and 5-year OS difference (HR = 1.06, 95% CI: 0.61-1.83, p = 0.843) was observed between cTACE-RFA (95.7%, 80.6%, 59.1%) and RFA alone group (96.8%, 78.5%, 61.3%). Subgroup analyses revealed significant OS improvements with cTACE-RFA in tumor with high-risk locations (HR = 0.38; 95% CI: 0.17-0.85, p = 0.018) and diameter 3-5 cm: (HR = 0.28; 95% CI: 0.12-0.64, p = 0.003). cTACE-RFA group also was observed significant LPFS improvements for tumors in high-risk locations (HR=0.48, 95% CI: 0.30-0.77, p=0.002) or 3-5 cm in size (HR=0.25, 95% CI: 0.15-0.41, p<0.001). Complication rates were comparable, with no procedure-related mortality and similar severe adverse event incidences (P=0.516).

Conclusion: cTACE-RFA significantly prolongs LPFS compared to RFA alone in early HCC, particularly for tumors >3 cm or in high-risk locations, without increasing major complications.