Journal of Hepatocellular Carcinoma最新文献

Purpose: The optimal timing for combining radiotherapy with immunotherapy in patients with hepatocellular carcinoma (HCC) remains uncertain and affects treatment efficacy and patient outcomes. This study aimed to evaluate and compare the efficacy and treatment-related adverse events (TRAEs) of synchronously administered radiotherapy and programmed cell death protein (PD)-1 inhibitors and sequential administration in patients with HCC.

Patients and methods: We retrospectively enrolled 67 patients with HCC who were undergoing liver radiotherapy and PD-1 inhibitor therapy at two medical centers between July 2017 and April 2023. Additionally, we created an experimental tumor model using 6-week-old female mice to validate our findings.

Results: In the concurrent group, the median overall survival was indefinite; however, it was 13 months in the sequential group (95% confidence interval [CI] 6.7-19.3 months, P=0.010). The median progression-free survival was significantly longer in the concurrent group (12 months, 95% CI 9.5-14.5 months) than in the sequential group (7 months, 95% CI 1.3-12.7 months; P=0.043). Grade 3/4 TRAEs occurred in 30.4% (concurrent) and 28.6% (sequential) of patients without any treatment-related deaths. In the mouse model, synchronous treatment significantly inhibited tumor growth compared to sequential treatment (293.4±45.18 mm³ versus 602.7±41.68 mm³; P=0.001). Flow cytometry revealed an increased Tregs/CD3⁺ T cell ratio and a decreased CD8⁺/Treg cell ratio post-radiotherapy, suggesting an immunosuppressive tumor microenvironment.

Conclusion: Synchronous treatment demonstrated superior efficacy in treating HCC compared to sequential treatment, with manageable adverse events. The rapid increase in Tregs after radiotherapy may contribute to the reduced efficacy of sequential radiotherapy plus PD-1 inhibitors.

Purpose: Type II diabetes mellitus (T2DM) has been found to increase the mortality of patients with hepatocellular carcinoma (HCC). Therefore, this study aimed to establish and validate a machine learning-based explainable prediction model of prognosis in patients with HCC and T2DM undergoing transarterial chemoembolization (TACE).

Patients and methods: The prediction model was developed using data from the derivation cohort comprising patients from three medical centers, followed by external validation utilizing patient data extracted from another center. Further, five predictive models were employed to establish prognosis models for 1-, 2-, and 3-year survival, respectively. Prediction performance was assessed by the receiver operating characteristic (ROC), calibration, and decision curve analysis curves. Lastly, the SHapley Additive exPlanations (SHAP) method was used to interpret the final ML model.

Results: A total of 636 patients were included. Thirteen variables were selected for the model development. The final random survival forest (RSF) model exhibited excellent performance in the internal validation cohort, with areas under the ROC curve (AUCs) of 0.824, 0.853, and 0.810 in the 1-, 2-, and 3-year survival groups, respectively. This model also demonstrated remarkable discrimination in the external validation cohort, achieving AUCs of 0.862, 0.815, and 0.798 in the 1-, 2-, and 3-year survival groups, respectively. SHAP summary plots were also created to interpret the RSF model.

Conclusion: An RSF model with good predictive performance was developed by incorporating simple parameters. This prognostic prediction model may assist physicians in early clinical intervention and improve prognosis outcomes in patients with HCC and comorbid T2DM after TACE.

Introduction: Hepatocellular carcinoma (HCC) disproportionately affects Hispanic persons with higher age-specific incidence and increased mortality rates compared to non-Hispanic Whites. These high rates of incidence and mortality may be explained by the variation in risk factors. Given the high prevalence of type 2 diabetes mellitus (DM) among the Hispanic population, we aimed to assess the risk and prognosis of HCC in Mexican Americans with type 2 DM with consideration of treatment for DM.

Methods: A case-control study of 241 Mexican American HCC patients and 500 healthy controls in Texas was conducted. Multivariable logistic regression analysis was performed to determine the association between type 2 DM and HCC risk while adjusting for other risk factors. Also, a restricted analysis of patients with type 2 DM was conducted to determine the effects of age at onset and duration of DM on HCC risk. Interactions among DM, heavy alcohol consumption, and viral hepatitis infection were examined. Overall survival was examined, and multivariable Cox proportional hazards regression analysis was performed for HCC patients with type 2 DM.

Results: The adjusted odds ratio (AOR) for DM was 2.74 (P < 0.01). Compared with patients who had DM for 2-10 years, those who had it for at least 20 years had an AOR of 4.60 (P = 0.04). Metformin use was associated with a reduced risk of death in HCC cases with type 2 DM, with a hazard ratio of 0.72 (P = 0.01) as compared with non-users.

Conclusion: Our results demonstrate that type 2 DM was independently associated with increased risk of HCC among Mexican Americans. Metformin use was associated with improved survival among HCC patients with type 2 DM. Type 2 DM significantly increased the risk of HCC alone and in conjunction with other parameters of metabolic syndrome in the Mexican American population after adjusting for other risk factors.

Background: The prognosis is extremely troubling in advanced hepatocellular carcinoma (HCC). Prognostic scores have been developed. Yet, the positive predictive values might appear inadequate. This retrospective study aimed to develop a quick and efficient risk score to assess prognosis and clinical response.

Methods: A total of 391 hCC patients were enrolled and were divided into training and validation groups between 2015 and 2024. Patients were separated into high-risk and low-risk groups using X-tile software. Using the COX proportional risk model analysis method, we then created a risk score and examined them using Kaplan-Meier, time-dependent receiver operating characteristics (ROC) curve, and nomogram analysis.

Results: In predicting overall survival (OS), free fatty acid/high-density lipoprotein cholesterol (FFHL), tumor size, and BCLC stage were independent prognostic variables. A new risk score was developed just above and used as a prognostic factor (p < 0.001 in the training and validation groups) and had a high time-dependent ROC for progress-free survival (PFS) (area under the curve [AUC] 0.688-0.789 in the training group; AUC 0.592-0.741 in the validation group) and OS (AUC 0.812-0.918 in the training group; AUC 0.692-0.981 in the validation group). In comparison to the best overall response (BOR), the score offered a more accurate evaluation of durable clinical benefit (DCB) (p < 0.001 in the training and validation group; p = 0.061 vs 0.001 in the training and validation group).

Conclusion: A new score based on lipid markers is a useful tool for evaluating prognosis and distinguishing patients with DCB.

The intratumoral microbiota, an integral part of liver tumors, has garnered significant attention from researchers due to its role in tumor development regulation and impact on cancer treatment. Intratumoral microorganism not only influences tumorigenesis and progression, but also serves as potential biomarkers and targets for tumor therapy. Targeted manipulation of these microorganisms holds great promise for personalized liver cancer treatment. However, there is a lack of systematic summaries and reports on the study of intratumoral microorganism in hepatocellular carcinoma. This comprehensive review aims to address this gap by summarizing research progress related to in the field of hepatocellular carcinoma intratumoral bacteria, including their sources, types, distribution characteristics within tumors, impact on tumor development, underlying mechanisms, and application prospects. Through the analysis, it is proposed that intratumor organisms can be used as markers for liver cancer diagnosis and treatment, drug carrier materials for targeting liver cancer tissues, and the research prospects of developing new combination therapies based on the in-depth understanding of the interactions between intratumor microorganisms and the tumor microenvironment, immune cells, liver cancer cells, etc. as well as exploring the prospects of developing new combination therapies based on these interactions. It is hoped that from the perspective of intratumoral microbiota, potential theoretical support can be provided for future research on targeted cancer therapy for liver cancer intratumoral microbiota, and new insights and ideas can be provided for targeting points and research methods in tumor research.

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.