Journal of Hepatocellular Carcinoma最新文献

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.

Introduction: Lenvatinib and sorafenib remain viable first-line (1L) options for patients ineligible for newer therapies. This study uses real-world data (RWD) to compare the effectiveness and safety of lenvatinib and sorafenib, addressing gaps between clinical trials and real-world practice.

Materials and methods: This retrospective, multi-center study utilized the Liver Cancer IN Korea (LINK) database, including HCC patients diagnosed between January 2015 and June 2022 who received 1L lenvatinib or sorafenib. Effectiveness and safety were assessed with real-world overall survival (rwOS), time to treatment discontinuation (rwTTD), time to next treatment (rwTTNT), and incidence of adverse events of special interest (AESI). Propensity score matching was employed to adjust for potential bias.

Results: Post-matching, lenvatinib demonstrated a longer median rwOS of 9.56 months (95% CI: 8.25-10.78) compared to 7.13 months (95% CI: 6.44-7.82) of sorafenib, and longer medians for rwTTD (3.65 months, 95% CI: 3.09-4.07 vs 2.04 months, 95% CI: 1.87-2.30) and rwTTNT (6.51 months, 95% CI: 5.62-7.62 vs 3.71 months, 95% CI: 3.45-4.34). Regarding AESI, lenvatinib was significantly associated with lower rates of hand-foot syndrome (incidence rate ratio, IRR 0.55, 95% CI: 0.33-0.88, p = 0.013) and most hepatotoxicity-related events, but a higher rate of proteinuria (IRR 2.40, 95% CI: 1.49-3.98, p < 0.001).

Conclusion: Leveraging RWD, our study demonstrated that 1L lenvatinib may offer a survival advantage over 1L sorafenib in HCC patients, with both treatments exhibiting safety profiles consistent with clinical trials. RWD complements clinical trials by validating long-term outcomes and addressing patient populations excluded from pivotal studies, guiding therapeutic decisions in clinical practice.

Purpose: Lenvatinib is an effective treatment for patients with intermediate- to advanced-stage unresectable hepatocellular carcinoma (HCC). However, tumor response and survival outcomes vary widely. Traditional machine learning (ML) models have been developed to predict treatment response or survival status at discrete time points. However, an overall prediction of overall survival (OS) and progression-free survival (PFS) incorporating censored survival data is lacking. We aimed to conduct a comprehensive survival analysis of OS and PFS by using ML-based survival models.

Patients and methods: This multicenter, retrospective study included patients with unresectable HCC receiving lenvatinib across five healthcare centers. Demographic data, laboratory results, tumor characteristics, and survival outcomes were collected. Five ML-based survival models were developed and compared using Harrell's concordance index (C-index). The predicted risk scores were used to stratify patients into low-, intermediate-, and high-risk groups and validated in the test set.

Results: 205 patients were included for training and validation. Among the five ML models, the GBM-Cox model achieved the highest C-indices for both OS (0.617) and PFS (0.645) prediction. The predicted risk scores stratified the patients into low-, intermediate-, and high-risk groups for OS (median, 18.7 vs 13.6 vs 8.8 months; p = 0.004) and PFS (median, 8.2 vs 4.0 vs 3.7; p = 0.017). The most influential prognostic factors included albumin-bilirubin (ALBI) score, alanine aminotransferase, and age for OS, and macrovascular invasion, ALBI score, and alpha-fetoprotein for PFS.

Conclusion: ML-based survival models successfully stratified patients into low-, intermediate-, and high-risk groups for OS and PFS. Key features included ALBI score and alanine aminotransferase for OS, and macrovascular invasion and ALBI score for PFS. These models have the potential to guide clinicians' treatment decisions and provide prognostic evaluations. Future prospective studies with larger cohorts, as well as integration of imaging biomarkers are warranted to optimize these predictive models.

Background: There is relatively scant evidence concerning the effects of Lenvatinib and Pembrolizumab together with TACE for advanced HCC Lenvatinib and pembrolizumab have been widely applied in clinical settings. PIVKA-II serving as the sensitive biomarker for evaluating liver cancer was employed by us to further assess the therapeutic effectiveness of TACE combined with Lenvatinib in the treatment of BCLC C.

Methods: In this retrospective study, 260 patients with HCC BCLC C stage were included in the present study. TACE (TL group) included 126 patients, TACE-Lenvatinib-Pembrolizumab (TPB group) consisted of 134 patients. OS and PFS were compared between the two groups. Alternatively, the impact of PIVKA-II in TPB on the PFS of BCLC C stage was also assessed.

Results: The median overall survival (OS) in the TL group was significantly prolonged compared to that in the TPB group (13.7 months versus 9.6 months). Conversely, the median progression - free survival (PFS) was extended in the TPB group as opposed to the TL group (9.3 months versus 6.2 months). The adverse events in the TPB group were controllable and tolerable. After six months of combined treatment, the change in PIVKA - II became less significant. This suggests that PIVKA-II is negatively correlated with PFS, meaning that the greater the decrease in PIVKA-II after 6 months of combined therapy, the longer the PFS time for the patient.

Conclusion: TACE combined with Lenvatinib and Pembrolizumab exhibited remarkable survival benefits for HCC BCLC C patients. Given the extremely dismal prognosis of advanced HCC, the safety and efficacy of TACE in combination with Lenvatinib and Pembrolizumab justify its clinical application.

Background: Transarterial chemoembolization (TACE) is the standard treatment for intermediate-stage hepatocellular carcinoma (HCC), but resistance to TACE is a major clinical challenge. This study aimed to identify genes associated with TACE refractoriness and their roles in HCC progression.

Methods: Gene expression profiles from 104 HCC patients treated with TACE were analyzed using unsupervised clustering to identify molecular subtypes. Key genes associated with TACE refractoriness were identified through univariate Cox regression and lasso, with ATP1B3 emerging as a candidate. Functional annotation of ATP1B3 was conducted using KEGG, GO, and GSEA analyses, while immune profiling and immunotherapy response were compared between ATP1B3-high and ATP1B3-low groups. Single-cell RNA sequencing (scRNA-seq) was employed to explore ATP1B3 expression and its cellular interactions. In vitro functional assays validated its role in migration, invasion, cell cycle, chemotherapy sensitivity, and apoptosis.

Results: Unsupervised clustering revealed two distinct molecular subtypes of HCC. Cluster 1 was associated with significantly prolonged overall and recurrence-free survival, whereas Cluster 2 exhibited aggressive tumor behavior and adverse clinical outcomes. ATP1B3 was identified as a pivotal gene linked to TACE refractoriness and poor prognosis. Elevated ATP1B3 expression was strongly correlated with metabolic dysregulation, heightened tumor aggressiveness, immune evasion, and diminished therapeutic responses to TACE, sorafenib, and immunotherapy. scRNA-seq analyses demonstrated widespread ATP1B3 expression across tumor and immune cell subsets, with ATP1B3-positive HCC cells displaying enhanced interactions with immune cells. Functional assays revealed that ATP1B3 overexpression promoted tumor migration, invasion, and chemoresistance, while its silencing induced cell cycle arrest, apoptosis, and increased sensitivity to cisplatin.

Conclusion: This study identifies TACE refractoriness-related gene ATP1B3 as a key regulator of tumor progression, immune evasion, and therapeutic resistance in HCC. These findings highlight ATP1B3 as a promising biomarker for patient stratification and a potential therapeutic target to improve clinical outcomes in HCC.

Objective: Dual-phenotype hepatocellular carcinoma (DPHCC) is a unique subtype of hepatocellular carcinoma (HCC) characterized by strong tumor stemness and invasive capabilities. ARID3A is identified as a potential regulator of tumor stemness in DPHCC by applying transcriptomic analysis. The precise mechanisms of ARID3A on the aggressive behavior of DPHCC remain to be further explored.

Materials and methods: In vitro functional experiments and in vivo tumorigenesis assays were used to validate the malignant behaviors of ARID3A. RNA sequencing was performed on ARID3A-transfected cells to identify ARID3A-mediated regulatory mechanisms. Finally, the impact of ARID3A-TNF-α/NF-κB axis on HCC malignant behavior was analyzed through in vitro blocking or stimulation experiments.

Results: The expression of ARID3A was upregulated in DPHCC and was associated with poor prognosis among these patients (p = 0.006, HR = 3.77, 95% CI:1.762-8.069). In vitro and in vivo experiments indicated that ARID3A facilitated stemness features and tumor progression. Findings from RNA-seq suggested that ARID3A enhanced tumor stemness and activated epithelial-mesenchymal transition through the activation of TNF-α-mediated NF-κB signaling. In vitro stimulation of ARID3A-transfected cells lines with recombinant TNF-α protein or inhibition of TNF-α-mediated NF-κB signaling regulated the ARID3A-mediated invasiveness.

Conclusion: Our study reveals that ARID3A acts as an oncogene and promotes aggressive features of stem-like cells in DPHCC via the ARID3A-TNF-α/NF-κB axis. Thus, it may facilitate the development therapeutic strategy for DPHCC.

Objective: To construct a radiomics-based model for predicting postoperative recurrence in hepatocellular carcinoma (HCC) patients with vessels encapsulating tumor clusters (VETC) positive based on CT scan.

Methods: This retrospective study enrolled patients who underwent surgical resection between January 2016 and January 2024 at Union Hospital, with pathologic confirmation of HCC and VETC status. An external test set was drawn from Chegu Hospital, covering January 2018 to January 2022. Tumor segmentation was performed on portal venous phase CT scan, and then radiomics features were extracted. These features were further analyzed using the LASSO algorithm and combined with clinical features to construct a radiomics-clinical combination model. Model performance was evaluated using receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA). Patients were divided into high- and low-risk groups based on model scores, and Kaplan-Meier (KM) curves were compared.

Results: A total of 243 patients were included (median age 56.7 years, 211 males). Nine radiomics features and two clinical features were selected to construct the combined model. The area under the ROC curve (AUC) for predicting 1-year recurrence was 0.898 (95% CI: 0.797-0.999) in the internal test set and 0.804 (95% CI: 0.641-0.967) in the external test set. Calibration curves and DCA demonstrated high net clinical benefit of the combined model. The median recurrence-free survival (RFS) of patients in the high-risk group was significantly lower than that in the low-risk group (internal test set: 13.5 vs 30.0 months, respectively. P=0.004; external test set: 13.0 vs 31.0 months, respectively. P< 0.0001).

Conclusion: The radiomics-clinical combination model showed high accuracy for preoperatively predicting recurrence in patients with VETC-positive HCC receiving hepatectomy.