Journal of Hepatocellular Carcinoma最新文献

Background: The combination of locoregional and systemic therapy may achieve remarkable tumor response for unresectable hepatocellular carcinoma (HCC).

Objective: We aimed to investigate the correlation between radiologic and pathologic responses following combination therapy, evaluate their prognostic values, and to establish a non-invasive prediction system for pathologic response.

Methods: This single-center retrospective study included 112 consecutive patients with HCC who underwent locoregional and systemic combination therapy followed by liver resection or transplantation. Radiologic response was assessed with Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 and modified RECIST (mRECIST). Pathologic necrosis percentage was assessed to determine major pathologic response (MPR, ≥90% tumor necrosis) and pathologic complete response (100% tumor necrosis). Performance of the response criteria in predicting pathologic response was assessed with the area under the receiver operator characteristic curve (AUC).

Results: Among all radiologic and pathologic response criteria, MPR was the only independent predictor of post-resection recurrence-free survival (RFS) (adjusted hazard ratio 0.34, 95% CI 0.16-0.72, p=0.004). In addition, mRECIST showed stronger correlation with pathologic response than RECIST 1.1 (spearman r values: 0.76 vs 0.42, p<0.001). A prediction system for MPR was developed that included a combination of mRECIST response (ie, >70% decrease of viable target lesions) with either >90% decrease in AFP (for AFP-positive group, n=75) or >80% decrease in PIVKA-II (for AFP-negative group, n=37), which yielded a respective AUC of 0.905 and 0.887. Furthermore, the system-defined dual-positive responders showed improved median RFS (not reached) than non-responders (7.1 months for AFP-positive group [p=0.043] and 13.3 months for AFP-negative group [p=0.099]).

Conclusion: mRECIST was more indicative of pathologic response after combination therapy than RECIST 1.1. Integration of mRECIST with AFP or PIVKA-II responses allowed for accurate prediction of MPR and could support decision-making on subsequent curative-intent treatment.

Purpose: Portal vein tumor thrombus (PVTT)-related severe symptomatic portal hypertension (SPH) leads to a poor prognosis in patients with advanced hepatocellular carcinoma (HCC). Traditional transjugular intrahepatic portosystemic shunt (TIPS) using covered plus bare stent can effectively relieve SPH, however, the bare segment is susceptible to obstruction due to PVTT invasion. This study aimed to evaluate the safety and efficacy of fully covered stent-TIPS (FCS-TIPS) for treatment of PVTT-related SPH in advanced HCC patients.

Patients and methods: This retrospective study enrolled 25 patients with advanced HCC who underwent FCS-TIPS for PVTT-related severe SPH from June 2018 to January 2024. The evaluated outcomes included overall survival (OS), technical success rate, reduction in portal venous pressure gradient (PPG), stent patency rate, SPH control rate, liver function and complications.

Results: The technical success rate was 100% without perioperative deaths or severe procedure-related adverse events. The average PPG decreased by 13.4±4.6 mmHg. The overall symptom control rate of SPH was 96.0%. Variceal bleeding, ascites/hydrothorax, and enteropathy control rates were 100%, 95.0%, and 100%, respectively. Liver function showed mild improvement one month after TIPS. One patient (4.0%) experienced overt hepatic encephalopathy (OHE) and three (12.0%) patients developed shunt dysfunction during the follow-up period. None of the patients experienced shunt-induced extrahepatic metastasis. The median OS was 6.0 months and the cumulative survival rates at 3, 6, 12 months were 80.0%, 52.0% and 21.3%.

Conclusion: FCS-TIPS is safe and effective for treating PVTT-related severe SPH and can serve as a bridging therapy for advanced HCC.

Background & aims: The effect of transarterial chemoembolization (TACE) plus radiofrequency ablation (RFA) (TACE-RFA) for hepatocellular carcinoma (HCC) in high-risk locations is not satisfactory. The aim of this study was to compare the clinical outcomes of TACE-RFA plus iodine-125 (¹²⁵I) seed implantation (TACE-RFA-¹²⁵I) therapy with those of TACE-RFA for unresectable HCC (≤5 cm) in high-risk locations.

Methods: From January 2010 to June 2023, the clinical data of 126 patients with unresectable HCC (≤5 cm) in high-risk locations who received TACE-RFA-¹²⁵I or TACE-RFA treatment were retrospectively analyzed. The clinical outcomes between the two groups were compared after propensity score matching (PSM) analysis.

Results: Forty-six pairs of patients were matched. The local progression-free survival rates at 1-, 2-, 3-, 4-, and 5-years were 100%, 82.4%, 74.8%, 63.5%, and 54% in the TACE-RFA-¹²⁵I group, which were significantly higher than 91.3%, 69.4%, 50.7%, 29.4%, and 26.7% in the TACE-RFA group, respectively (p = 0.004). The median progression-free survival in the TACE-RFA-¹²⁵I group was significantly longer than that in the TACE-RFA group (p = 0.002). The overall survival rates at 1-, 2-, 3-, 4-, and 5-years were 100%, 93.4%, 80.7%, 74.9%, and 64.7% in the TACE-RFA-¹²⁵I group, which were significantly higher than 97.8%, 78%, 68.6%, 51.1%, and 45.3% in the TACE-RFA group, respectively (p = 0.011). There was no occurrence of major complications or procedure-related deaths in the two groups.

Conclusion: Compared with the TACE-RFA treatment, TACE-RFA-¹²⁵I should be a more effective treatment strategy for patients with unresectable HCC (≤5 cm) in high-risk locations.

Objective: This study aimed to investigate how dynamic contrast-enhanced CT imaging signs correlate with the differentiation grade and microvascular invasion (MVI) of hepatocellular carcinoma (HCC), and to assess their predictive value for MVI when combined with clinical characteristics.

Methods: We conducted a retrospective analysis of clinical data from 232 patients diagnosed with HCC at our hospital between 2021 and 2022. All patients underwent preoperative enhanced CT scans, laboratory tests, and postoperative pathological examinations. Among the 232 patients, 89 were identified as MVI-positive and 143 as MVI-negative. Regarding tumor differentiation, 56 patients were well-differentiated, 145 moderately, and 31 poorly. Multivariate logistic regression analysis was employed to establish a prediction model for variables showing significant differences. Additionally, the diagnostic performance of various indicators were evaluated using ROC analysis.

Results: Among the qualitative data, significant differences (P<0.05) were observed between the MVI-positive and MVI-negative groups in 5 items such as peritumoral enhancement. In terms of quantitative data, the MVI-positive group exhibited higher maximum tumor length, AST, ALT, AFP levels and the ALBI score (P<0.05). Conversely, CT values in the arterial phase (AP), portal venous phase (PVP), and PT levels were lower in the MVI-positive group (P<0.05). Multivariate Logistic regression analysis identified ALBI score, PT level, CT value in PVP, and tumor capsule as independent risk factors for MVI occurrence (AUC: 0.71, 0.58, 0.66, and 0.60). The combined diagnostic AUC value was 0.82 (95% CI: 0.76-0.87). Significant differences were found among different differentiation grade groups in 10 items such as non-smooth tumor margin (P<0.05).

Conclusion: Preoperative dynamic contrast-enhanced CT examination in patients with HCC can be utilized to predict the presence of MVI. When combined with clinical characteristics, these imaging signs demonstrate good predictive performance for MVI status. Furthermore, this approach has significant implications for determining the differentiation grade of tumors.

Purpose: Camrelizumab and rivoceranib together provide a new first-line treatment approach for unresectable hepatocellular carcinoma (HCC). Meanwhile, transarterial chemoembolization (TACE) is an effective method for the local control of the HCC. The study compared the clinical benefit and safety between TACE with camrelizumab-rivoceranib and camrelizumab-rivoceranib alone for Barcelona Clinic Liver Cancer (BCLC)-C HCC patients.

Patients and methods: This multi-center retrospective analysis included continuous BCLC-C HCC patients who received camrelizumab-rivoceranib with TACE and camrelizumab-rivoceranib alone from January 2020 to December 2022. The therapeutic response, progression-free survival (PFS), safety, and overall survival (OS) were compared. The quantitative data were compared via the t-test or Mann-Whitney U-test. Comparison of the categorical data was done by chi-square or Fisher's exact tests. The comparison of PFS with OS was compared by Log rank test. A Multivariate Cox regression test was utilized to identify risk variables for both PFS and OS.

Results:  This analysis comprised 132 BCLC-C HCC patients who received camrelizumab-rivoceranib alone (n = 74) or combined treatment (n = 58). The combined group displayed higher partial response (44.8% vs 21.6%, p = 0.004) and total response (55.2% versus 36.5%, p = 0.032) rates than camrelizumab-rivoceranib alone group. The median PFS (13.5 months vs 10.3 months, p = 0.046) and OS (22.8 months vs 18.4 months, p = 0.041) for the combined group was significantly longer relative to the camrelizumab-rivoceranib alone group. Additional risk factors, excluding the therapy option, were a higher alpha-fetoprotein level and Eastern Cooperative Oncology Group performance status. The incident rates of camrelizumab-rivoceranib-related advents were comparable between combined and camrelizumab-rivoceranib alone groups (46.3% vs 51.4%, p = 0.572). The combined group contained 33 patients (56.9%) who experienced temporary post-embolization symptoms.

Conclusion: For BCLC-C HCC patients, TACE may significantly increase the therapeutic effectiveness of camrelizumab-rivoceranib without increasing the risk of camrelizumab-rivoceranib-related complications.

Hepatocellular carcinoma (HCC) is the most prevalent malignant tumor, characterized by a poor prognosis. In recent decades, both the incidence and mortality rates of HCC have risen sharply. Sorafenib has emerged as the first conventional drug approved by the US Food and Drug Administration for first-line treatment in advanced HCC patients due to its favorable safety profile. However, its effectiveness is severely hindered by acquired drug resistance, which leads to only approximately 30% of HCC patients benefited from sorafenib therapy. Sorafenib resistance involves various mechanisms that inhibit cellular uptake of iron and reactive oxygen species (ROS). Consequently, ferroptosis a novel form of cell death contingent upon the accumulation of intracellular iron and ROS plays a critical role in mediating sorafenib resistance through the Hippo YAP pathway or Keap1-Nrf2 system. This review aimed to comprehensively elucidate the mechanisms underlying sorafenib resistance in HCC, particularly focusing on ferroptosis and its pathways, to provide valuable insights into targeting ferroptosis or its pathways for sorafenib-resistant HCC treatment.

Objective: To evaluate the baseline albumin-bilirubin (ALBI) grade's role in advanced hepatocellular carcinoma (HCC) receiving transarterial chemoembolization (TACE) plus anti-angiogenesis therapies and PD-1 inhibitors (TACE+TP) versus anti-angiogenesis therapies and PD-1 inhibitors (TP).

Methods: This multicenter retrospective study enrolled advanced HCC undergoing TACE+TP or TP from January 2019 to June 2023 at three hospitals in China. The primary outcomes were time to progression of the ALBI grade and change in ALBI score between the initial baseline and the final assessment point available, the secondary outcomes consisted of overall survival (OS) as well as progression-free survival (PFS).

Results: One hundred and eighty-three patients were ultimately enrolled in this study for analysis, of whom 44 were categorized as having an ALBI grade 1 (TACE+TP, n = 23; TP, n = 21) and 139 were classified as ALBI grade 2 (n = 77; n = 62). Time to progression of the ALBI grade, indicating liver function deterioration, was comparable between the TACE+TP and TP groups (median, 11.2 vs 19.3 months; P = 0.353). Change in ALBI score between the initial baseline and the final assessment point available was comparable among the two groups (difference in least squares mean, 0.084). Irrespective of the initial ALBI grade, patients in TACE+TP group exhibited a significant enhancement in OS and displayed a promising trend towards better PFS.

Conclusion: TACE+TP had no negative influence on liver function and enhanced survival regardless of baseline ALBI grade when compared to TP in advanced HCC patients.

Objective: To develop and validate a deep learning-based automatic segmentation model and combine with radiomics to predict post-TACE liver failure (PTLF) in hepatocellular carcinoma (HCC) patients.

Methods: This was a retrospective study enrolled 210 TACE-trated HCC patients. Automatic segmentation model based on nnU-Net neural network was developed to segment medical images and assessed by the Dice similarity coefficient (DSC). The screened clinical and radiomics variables were separately used to developed clinical and radiomics predictive model, and were combined through multivariate logistic regression analysis to develop a combined predictive model. The area under the curve (AUC), calibration curve, and decision curve analysis (DCA) were applied to compare the performance of the three predictive models.

Results: The automatic segmentation model showed satisfactory segmentation performance with an average DSC of 83.05% for tumor segmentation and 92.72% for non-tumoral liver parenchyma segmentation. The international normalized ratio (INR) and albumin (ALB) was identified as clinically independent predictors for PTLF and used to develop clinical predictive model. Ten most valuable radiomics features, including 8 from non-tumoral liver parenchyma and 2 from tumor, were selected to develop radiomics predictive model and to calculate Radscore. The combined predictive model achieved the best and significantly improved predictive performance (AUC: 0.878) compared to the clinical predictive model (AUC: 0.785) and the radiomics predictive model (AUC: 0.815).

Conclusion: This reliable combined predictive model can accurately predict PTLF in HCC patients, which can be a valuable reference for doctors in making suitable treatment plan.

Purpose: To investigate the differences of combined hepatocellular carcinoma-cholangiocarcinoma (cHCC-CCA) patients with a cholangiocarcinoma (CCA) component ≥ 30% or < 30% versus intrahepatic cholangiocarcinoma (iCCA) patients in recurrence-free survival (RFS) and overall survival (OS) prognoses.

Methods: Patients with cHCC-CCA and iCCA after surgery were recruited. All cHCC-CCA patients were divided into two subgroups (CCA components ≥ 30% and < 30%). Then, Kaplan-Meier survival analysis and Cox regression analysis were used to investigate and compare the differences of cHCC-CCAs with a CCA component ≥ 30% or < 30% versus iCCAs in RFS and OS prognoses, respectively. The differences of MRI features between cHCC-CCAs with a CCA component ≥ 30% and < 30% were also compared.

Results: One hundred sixty-four cHCC-CCAs and 146 iCCAs were enrolled. Compared with iCCAs, cHCC-CCAs with a CCA component < 30% had better OS prognosis (HR: 2.888, p = 0.045). However, Cox regression analysis revealed that cHCC-CCAs with a CCA component ≥ 30% had poorer RFS (HR: 0.503, p < 0.001) and OS (HR: 0.58, p = 0.033) prognoses than iCCAs. In addition, rim APHE (OR = 0.286, p < 0.001), targetoid diffusion restriction (OR = 0.316, p = 0.019), corona enhancement (OR = 0.481, p = 0.033), delayed enhancement (OR = 0.251, p = 0.001), and LR-M (OR = 1.586, p < 0.001) were significant factors associated with cHCC-CCAs with a CCA component ≥ 30%. Multivariable regression analyses showed that only LR-M (OR = 1.522, p = 0.042) was a significantly independent predictor for cHCC-CCAs with a CCA component ≥ 30%.

Conclusion: cHCC-CCAs with a CCA component ≥ 30% had worse prognoses than iCCAs. Therefore, we suggest that the postoperative treatment of cHCC-CCAs with a CCA component ≥ 30% can be based on the treatment strategy for iCCAs.