The clinical management of hepatocellular carcinoma (HCC) is strongly influenced by several prognostic factors, mainly tumor stage, patient's health, liver function and specific characteristics of each intervention. The interplay between these factors should be carefully evaluated by a multidisciplinary tumor board. To support this, the novel "multiparametric therapeutic hierarchy" (MTH) concept has been recently proposed. This review will present the main features of available surgical treatments for HCC (liver transplantation, liver resection, ablation). Strengths and weaknesses are reported in the light of clinical decision making and of treatment allocation, with a special focus on the collocation of each treatment in the MTH framework and on how MTH may be useful in supporting clinical decision. Sequential treatments and their role to allow further surgical treatments will also be analyzed.

Budd-Chiari syndrome-hepatocellular carcinoma (BCS-HCC) is uncommon and its molecular pathogenesis is poorly understood. In this study, we aimed to investigate the genomic landscape of BCS-HCC through whole exome sequencing (WES) to elucidate the cellular and molecular pathways involved in its pathogenesis.

We enrolled BCS-HCC (n = 13) and BCS alone (n = 73) patients. WES was performed using the Twist Comprehensive Exome kit on the Illumina platform, followed by quality checks and analysis using the GATK pipeline. Pathogenic/likely pathogenic variants were filtered out from the exonic part of the annotated variant calling file. rsIDs and Cosmic IDs (catalogue of somatic mutations in cancer) were assigned using dbSNP and Cosmic ID databases. Kyoto Encyclopaedia of Genes and Genomes (KEGG) and Gene ontology analysis were done for pathogenic gene variants.

We observed 1849 significant mutations in 305 genes in BCS-HCC patients, including missense, Indel, and frameshift mutations. Missense variants were more common than frameshift and indels in all subjects. The pathogenic mutations were found in 34 genes-cancer-causing (18 genes) and disease-causing (16 genes, both BCS or BCS-HCC) as per COSMIC cancer gene census. Pathogenic mutations were frequently observed in the mucin family genes including MUC3A, MUC4, MUC6, and MUC16 in BCS-HCC subjects. Changes in extracellular matrix and glycosylation were observed in gene ontology analysis of the genes having pathogenic variants.

Mutations in the mucin gene family including other cancer-causing genes were associated with BCS-HCC in our cohort. Larger, multicentric studies with regional and ethnic diversity are required to validate these findings.

While the CT-based method of detecting clinically significant portal hypertension (CSPH) emerged as a noninvasive alternative for evaluating CSPH, its predictive ability for post-hepatectomy outcomes is unknown. Therefore, this study aimed to evaluate the impact of CT-based CSPH on outcomes following hepatectomy for hepatocellular carcinoma (HCC).

This retrospective single-center study included patients with advanced chronic liver disease (ACLD) who underwent hepatectomy for very early or early-stage HCC between January 2017 and December 2018. CSPH was assessed using CT-based criteria, which included splenomegaly determined by deep learning-based spleen volume measurements with personalized reference thresholds, and the presence of gastroesophageal varices (GEV), spontaneous portosystemic shunt or ascites. Logistic regression and competing risk analyses were used to identify factors associated with severe post-hepatectomy liver failure (PHLF), hepatic decompensation, and liver-related death or transplantation. The predictive performance of existing models for PHLF was compared using both CT-based and conventional CSPH criteria (endoscopic GEV or splenomegaly with thrombocytopenia).

Among 593 patients (460 men; mean age 57.9 ± 9.3 years), 41 (6.9%) developed severe PHLF. The median follow-up period was 62 months. CT-based CSPH independently predicted severe PHLF (OR 7.672 [95% CI 3.209-18.346]), hepatic decompensation (subdistribution hazard ratio (sHR) 4.518 [1.868-10.929]), and liver-related death or transplantation (sHR 2.756 [1.315-5.773]). When integrated into existing models, CT-based CSPH outperformed conventional CSPH in predicting severe PHLF (AUC 0.724 vs. 0.694 for EASL algorithm (p = 0.036) and 0.854 vs. 0.830 for Wang's model (p = 0.011)).

CT-based CSPH is a strong predictor of poor post-hepatectomy outcomes in HCC patients with ACLD, offering a noninvasive surgical risk assessment tool.

Question Can CT-based detection of clinically significant portal hypertension (CSPH) serve as a noninvasive predictor of post-hepatectomy outcomes in hepatocellular carcinoma (HCC) patients? Findings CT-based CSPH independently predicted severe post-hepatectomy liver failure, hepatic decompensation, and liver-related death or transplantation, outperforming conventional CSPH criteria in predictive performance. Clinical relevance CT-based CSPH offers a noninvasive and effective tool for surgical risk assessment in HCC patients, potentially improving the selection of candidates for hepatectomy and optimizing patient outcomes.

Liver cancer is the third leading cause of cancer-related deaths worldwide, with hepatocellular carcinoma (HCC) accounting for approximately 90% of primary liver cancers. Advances in diagnostic and therapeutic tools, along with improved understanding of their application, are transforming patient treatment. Integrating these innovations into clinical practice presents challenges and necessitates guidance. These clinical practice guidelines offer updated advice for managing patients with HCC and provide a comprehensive review of pertinent data. Key updates from the 2018 EASL guidelines include personalised surveillance based on individual risk assessment and the use of new tools, standardisation of liver imaging procedures and diagnostic criteria, use of minimally invasive surgery in complex cases together with updates on the integrated role of liver transplantation, transitions between surgical, locoregional, and systemic therapies, the role of radiation therapies, and the use of combination immunotherapies at various stages of disease. Above all, there is an absolute need for a multiparametric assessment of individual risks and benefits, considering the patient's perspective, by a multidisciplinary team encompassing various specialties.

The optimal prognostic assessment for patients with hepatocellular carcinoma (HCC) after drug-eluting bead transarterial chemoembolization (DEB-TACE) remains unclear. This study aimed to propose a novel staging system in comparison with the current staging systems for HCC following DEB-TACE.

From four centers, patients with HCC undergoing DEB-TACE as the initial therapy were retrospectively included and classified into training and validation sets. Multivariable regression was used to determine the independent prognostic factors in the training set. A novel staging system incorporating the independent factors was proposed and externally validated in terms of discrimination and calibration compared to other staging systems in both sets.

The training and validation sets included 335 and 99 patients, respectively. Multivariable regression revealed independent factors including alpha-fetoprotein level, aspartate aminotransferase to lymphocyte count ratio index, maximum tumor diameter, Child-Pugh class, and portal vein invasion. The novel prognostic staging system, named PADCA, was proposed and outperformed other staging systems with the highest C-index, area under the curve, Wald test value, clinical benefit, and the lowest Akaike information criterion in the training and validation sets.

The PADCA staging system has a superior prognostic predictive ability compared to the current staging systems. PADCA can assist clinicians in screening out the patients most likely to derive benefit from DEB-TACE and guiding the formulation of therapy and follow-up strategy.

Purpose: To evaluate the use of yttrium-90 (Y90) dosimetry in predicting treatment outcomes when used following transarterial radioembolization with SIR-Spheres® (Resin Y90) in patients with hepatic tumors. Materials and Methods: This single institution retrospective analysis included 100 patients with hepatocellular carcinoma, colorectal carcinoma or other liver metastases who underwent transarterial radioembolization with resin Y90 and had imaging follow-up within one year of treatment. Mean tumor dose and mean dose to nontumor was calculated using voxel-based dosimetry software. Descriptive statistics were reported and methods of analyses included simple and multivariable linear regression, contingency table analyses, Kaplan-Meier estimation, and Cox proportional hazards models. Results: Of 100 patients included, 65 demonstrated tumor shrinkage following transarterial radioembolization. Of these, 20 (30.8%) had hepatocellular carcinoma, 22 (33.8%) had colorectal carcinoma, and 23 (35.4%) had other types of metastases. There was an association between tumor shrinkage and mean tumor dose (p = 0.0285) and mean dose to nontumor (p = 0.0028) in hepatocellular carcinoma patients, but not colorectal carcinoma, or the other subgroup. For all 100 patients, time to death and mean tumor dose was associated only in the other subgroup (p = 0.0260), but not in the hepatocellular or colorectal carcinoma groups. Time to death and mean dose to nontumor was associated in hepatocellular carcinoma patients (p = 0.0421), but not the colorectal carcinoma or other subgroup. Conclusions: Voxel-based dosimetry assessment is a tool that may be utilized to assist in predicting treatment outcomes in responders to transarterial radioembolization.

The EASL diagnostic algorithm for hepatocellular carcinoma, currently in use, dates back to 2018. While awaiting its update, numerous advancements have emerged in the field of hepatocellular carcinoma imaging. These innovations impact every step of the diagnostic algorithm, from surveillance protocols to diagnostic processes, encompassing aspects preceding a patient's inclusion in surveillance programs as well as the potential applications of imaging after the hepatocellular carcinoma diagnosis. Notably, these diagnostic advancements are particularly evident in the domain of magnetic resonance imaging. For example, the sensitivity of ultrasound in diagnosing very early-stage and early-stage hepatocellular carcinoma during the surveillance phase is very low (less than 50%) and a potential improvement in this sensitivity value could be achieved by using abbreviated protocols in magnetic resonance imaging. The aim of this review is to explore the 2024 updates in magnetic resonance imaging for hepatocellular carcinoma, with a focus on its role in surveillance, nodular size assessment, post-diagnosis imaging applications, and its potential role before the initiation of surveillance.

Liver transplantation (LT) is a promising treatment option for patients with hepatocellular carcinoma (HCC) comorbid with cirrhosis. However, HCC with portal vein tumor thrombosis (PVTT) remains an absolute contraindication for LT. This study aimed to analyze the outcomes of LT in patients with HCC plus portal vein thrombosis and further evaluate the impact of PVTT on the long-term outcomes of patients.

Among the 501 patients who underwent LT for HCC between January 2000 and March 2023, 29 (5.8%) patients with HCC who had portal vein thrombosis were further analyzed. Of these 29 patients with portal vein thrombosis, 12 (41.4%) were preoperatively diagnosed with PVTT and underwent LT after receiving downstaging therapy. The remaining 17 (58.6%) patients were PVTT-free prior to LT.

Overall, the recurrence-free survival rates at 1, 3, and 5 years were 96.3%, 74.2%, and 74.2%, respectively, while the 1-, 3-, and 5-year overall survival rates were 82.4%, 74.2%, and 70.1%, respectively. However, patients with viable PVTT had significantly worse outcomes than those without viable PVTT (p = 0.030). The 5-year recurrence-free and overall survival rates for patients with viable PVTT were 57.5% and 57.0%, respectively.

LT may still be a promising option for patients with HCC and PVTT after appropriate downstaging. However, caution should be adopted, as remnant viable PVTT might lead to unsatisfactory outcomes after transplantation.

Both irreversible electroporation (IRE) and radiofrequency ablation (RFA) are viable ablation methods for localized treatment of liver tumors. We conducted a meta-analysis to access the efficacy and safety of IRE and RFA in liver cancer treatment. Clinical studies on IRE and RFA for the treatment of liver cancer were collected from PubMed and CNKI until June 2023. We screened the literature for ablation success rates at 1 month post-operation, extracting keywords such as "ablation success rate," "technical success rate," "recurrence rate," and "complication" for meta-analysis. A total of 37 articles were included: 24 related to RFA involving 1,685 cases and 13 related to IRE involving 524 cases. The results demonstrate that ablation success rates at post-operative 1 month for IRE and RFA were 86% (95% CI: 82-89%) and 87% (95% CI: 81-92%), respectively. Technical success rates were 96% (95% CI: 88-100%) and 99% (95% CI: 96-100%). In addition, the recurrence rate was 16% (95% CI: 12-22%) in RFA group and 16% (95% CI: 9-23%) in IRE group. In terms of safety, the RFA had a complication rate of 28% (95% CI: 10-50%) and the IRE had a rate of 26% (95% CI: 13-43%). In conclusion, IRE and RFA exhibit similar ablation success rates at 1 month post-operation and comparable complication rates, making them both safe and effective treatment options.

To evaluate the efficacy of transarterial chemoembolization (TACE) combined with radiofrequency ablation (RFA) for both primary and recurrent early-stage hepatocellular carcinoma (HCC) and to analyze the significant prognostic factors.

Data from patients with early-stage primary or recurrent HCC who underwent TACE plus RFA between August 2019 and May 2024 were collected from three major general hospitals. 158 patients were divided into a primary group and a recurrent group on the basis of their baseline characteristics. Compared the objective response rate (ORR), 1-, 3-, and 5-year progression-free survival (PFS) rates, 1-, 3-, and 5-year overall survival (OS) rates, and complication rate between the two groups. Multivariate analyses were used to evaluate the factors influencing PFS and OS.

One hundred fifty-eight patients were enrolled. The ORRs of the primary and recurrent groups were 98.2% and 95.1%, respectively, with no statistically significant difference (χ2= 2.032, Ρ = 0.362). The primary group having a significantly longer PFS time than the recurrent group (Ρ < 0.001). However, there was no significant difference in the 1-, 3-, and 5-year OS rates between the two groups (Ρ = 0.218). Multivariate analysis revealed that primary or recurrent HCC and the Child‒Pugh score were significant prognostic factors for PFS, whereas the serum albumin level was a significant prognostic factor for OS.

TACE plus RFA has similar clinical efficacy and safety for both primary and recurrent early HCC. Compared with patients with primary HCC, those with recurrent disease had significantly shorter PFS times.

This study aimed to propose a novel approach of lipiodol combined with drug-eluting beads transarterial chemoembolization (Lipiodol-DEB TACE) and to compare the safety and efficacy with DEB-TACE alone for patients with unresectable hepatocellular carcinoma (HCC).

From the database of four centers, the records of patients with HCC who received DEB-TACE or Lipiodol-DEB TACE as initial treatment were retrospectively evaluated. The tumor response was measured based on the Modified Response Evaluation Criteria in Solid Tumors. Overall survival (OS), progression-free survival (PFS) and adverse events (AEs) were compared between two groups.

A total of 244 patients were included with 160 patients receiving DEB-TACE and 84 patients receiving Lipiodol-DEB TACE. Lipiodol-DEB TACE group had higher objective response rate (86.9 % vs. 76.3 %), higher disease control rate (97.6 % vs. 88.8 %), longer median OS (42.6 vs. 25.8 months) and longer median PFS (34.0 vs. 17.0 months) than DEB-TACE group (P < 0.05). There was no significant difference observed in the incidence of AEs between two groups. Cox analysis identified total bilirubin level, maximum tumor diameter, TACE method and portal vein invasion as independent prognostic factors.

Lipiodol-DEB TACE was a safe option and associated with improved tumor response and survival outcome compared to DEB-TACE alone for selected patients with HCC.

β-1,4-N-acetylgalactosaminyltransferase I (B4GALNT1) is a key glycosyltransferase for gangliosides. Its aberrant expression has been observed in various cancers, and its potential roles in tumor immunity were suggested recently. However, how B4GALNT1 regulate tumor progression and tumor immunity remains largely unknown. In this study, we aimed to investigate the roles of B4GALNT1 in hepatocellular carcinoma (HCC), particularly in reshaping the tumor immune microenvironment, and evaluate the potential beneficial effects of targeting B4GALNT1 in immunotherapy. Our data verified the aberrant upregulation of B4GALNT1 in HCC tumor tissues and tumor cells, which could be utilized as an independent prognostic factor and improve the predicting performance of traditional tumor node metastasis (TNM) system. We also demonstrated that B4GALNT1 increased the phosphorylation of Hes Family BHLH Transcription Factor 4 (HES4) via p38 mitogen-activated protein kinase (p38)/ c-Jun N-terminal kinase (JNK) signaling in tumor cells, thus increasing the transcriptional activity of HES4, which upregulated the synthesis and secretion of secreted phosphoprotein 1 (SPP1), modulated the composition of tumor-associated macrophages (TAMs) and T helper type 2 (Th2) cells, and eventually reshaped the immunosuppressive microenvironment. In addition, silencing B4GALNT1 was proved to enhance the tumor-killing efficiency of the programmed cell death protein 1 (PD-1)-targeting strategy in mouse model. In conclusion, this study evaluated B4GALNT1 as a prognostic predictor for HCC patients and revealed the mechanism of B4GALNT1 in microenvironmental remodeling, which extends the understanding of HCC progression and provides a novel auxiliary strategy for HCC immunotherapy.

For patients with hepatocellular carcinoma (HCC), stereotactic body radiation therapy (SBRT) has emerged as a locoregional treatment. Our purpose was to report outcomes in patients with HCC with Child-Pugh A (CP A) versus Child-Pugh B or C (CP B/C) liver dysfunction treated with SBRT.

A retrospective analysis of 80 patients with HCC, with a total of 94 tumors treated with SBRT, was conducted at a single institution. Outcomes were compared between patients with CP A (n = 51) and CP B/C (n = 29) liver dysfunction. Outcomes of interest included local control, overall survival (OS), and toxicity.

Median tumor size was 3.2 cm. There were 59 tumors included in the CP A cohort and 35 tumors in the CP B/C cohort. Median radiation dose was 50 Gy in 5 fractions for the CP A cohort and 40 Gy in 5 fractions for the CP B/C cohort. The rates of pathologic complete response were similar between the 2 groups at 63% for the CP A group and 61% for the CP B/C group. The estimated 1-year local control rates were similar between the 2 groups at 93% for the CP A group and 91% for the CP B/C group (P = .59). The 1-year OS for the CP A group was 85%, whereas the 1-year OS for the CP B/C group was 61% (P = .19). There was a 5.9% rate of grade 3+ toxicity in the CP A group and a 20.7% rate of grade 3+ toxicity in the CPB/C group.

Our findings suggest that SBRT is feasible and effective in patients with both CP A and CP B/C liver dysfunction with similar rates of local control and pathologic complete response despite lower radiation doses in the CP B/C cohort. In patients with more advanced CP B/C cirrhosis, toxicities were higher and must be weighed against possible treatment benefits. Further studies characterizing the optimal role of SBRT in patients with advanced cirrhosis are warranted.

This study aims to analyze the magnetic resonance imaging (MRI) change patterns of viable hepatocellular carcinomas (HCCs) following the initial transarterial chemoembolization (TACE).

A retrospective analysis of HCC patients' initial TACE from February 2015 to October 2022 across three centers and a clinical trial (NCT03113955) was conducted. The viability of residual HCCs at one and six months after TACE was evaluated using the LI-RADS Treatment Response Algorithm (LR-TRA) v2024. The radiological and radiomics features of post-TACE viable tumors between baseline and one-month, and between one- and six- months were compared using Wilcoxon signed-rank test and McNemar's test.

A total of 160 viable tumors were included in the study. Viable tumors at one month after TACE exhibited higher T1WI intensity (P =.024), lower T2WI intensity (P =.005), fewer washout features (P <.001), smaller size (P <.001), and higher ADC values (P <.001) compared to baseline HCC imaging.A significant reduction in DWI intensity (P =.002) and ADC values (P <.001) were observed in viable tumors at one month compared to those at six months. There were 82 (45.1%) radiomics features that changed significantly between the baseline and one-month. Only three radiomics features showed statistically significant difference of viable tumors between one- and six-month.

Compared to the baseline, viable HCCs after TACE demonstrated significant changes of imaging characteristics in a series of radiological and radiomics features at one- and six-month follow-ups.

Clinically diagnosing of viable HCCs using radiological methods is challenging. A comprehensive analysis of these imaging characteristics can facilitate the accurate identification of viable tumors.

Background: Liver transplantation (LT) is a method for treating hepatocellular carcinoma (HCC) with satisfactory outcomes. One of the novel methods for predicting LT outcomes is the Metroticket 2.0 model. The disease in patients initially within the Milan criteria (MC) may progress while on a transplantation waitlist; thus, various transplantation bridging therapy (BT) methods are proposed for patients to stay within the MC and optimize the LT outcome. Methods: We performed a retrospective analysis of patients who underwent LT for HCC at an oncological and transplantation center in northern Poland. Patients who underwent (n = 10) or did not undergo (n = 11) BT were included. The primary endpoints of the study were mortality among the patients, HCC recurrence, and Metroticket 2.0 scores based on LT qualification results and explant pathology outcomes. The median follow-up length was 44.03 months. Results: Patients who underwent BT had significantly lower Metroticket 2.0 scores and greater AFP concentrations at baseline. At LT, there was no significant difference in Metroticket 2.0 scores or AFP concentrations between the groups. Explant Metroticket 2.0 scores were significantly lower in patients who received BT. A complete pathologic response was achieved in 30.0% of patients who underwent BT. The recurrence-free survival rates were 100% and 90.91% in patients who underwent and did not undergo BT, respectively. Overall survival was 80.0% and 81.81% in patients who underwent and did not undergo BT, respectively. Conclusions: BT should be considered only as a means of remaining within the LT criteria. Routine BT does not appear to be justified for LT patients.

This study aims to assess the incidence and characteristics of all cancers, hepatocellular carcinoma (HCC), and extrahepatic cancers in patients with cirrhosis of various etiologies.

Prospective cohort study in patients with cirrhosis but no cancer, followed every 6-9 months through the HCC early detection program. Cancer incidence was compared with Spanish population data to calculate standardized incidence ratios (SIR), and cumulative incidence was calculated separately for cancer and competing events. Longitudinal outcomes were assessed with multivariate Fine-Gray and Cox regression models.

A total of 215 patients (68.4% male, median age 61 years) were included. Cirrhotic etiology was alcohol (38%), hepatitis B or C virus infection (36%), alcohol plus hepatitis B or C virus infection (9%), and other causes (17%). Sixty percent were current or former smokers. Thirty-nine cancers were observed (56% liver cancer), while 3.3 were expected (SIR 11.7; 95% confidence interval [CI] 8.6-16.1). Ten (4.6%) patients were censored for liver transplantation and 34 (15.8%) for death, constituting relevant competing risks. Smoking was significantly associated with overall cancer incidence (smokers: subdistribution hazard ratio [SHR] 3.14, 95% CI 1.33-7.38; former smokers: SHR 2.54, 95% CI 1.08-5.98). In the multivariable regression analysis, viral etiology, Child-Pugh score (B or C versus A), and smoking were associated with liver cancer, and smoking with extrahepatic cancer.

Patients with cirrhosis have an 11-fold risk of cancer compared to the general population. Risk is increased in liver and non-liver cancers. Active surveillance of any type of cancer and smoking cessation interventions are needed in these patients.

Transarterial chemoembolization (TACE) is recommended as a palliative treatment for patients of the B stage of the Barcelona Clinic Liver Cancer (BCLC) classification.

To identify clinical, biological, and radiological predictors of survival in patients undergoing TACE and develop a pre-therapeutic prognostic score.

191 adult cirrhotic patients treated for HCC with TACE at the University Hospital (UH) of Clermont-Ferrand (France) from 2007-2017 were retrospectively included. We investigated the impact of baseline liver function, patient characteristics, and tumor burden on overall survival and developed a prognostic score.

Patients had a median age of 66 years and 126 patients were Child A. The AFP-DIAM score distinguishes two groups with a significant difference in survival time (median OS 28.3 months in patients with a score = 0 versus 17.7 months in patients with a score > 0). AFP-DIAM was validated on an external cohort, is well calibrated, and has the best discrimination capacity (C-index) as compared to NIACE, HAP, STATE, and SIX TO TWELVE. AFP-DIAM and SIX TO TWELVE are the more easy-to-use scores. When AFP-DIAM and the SIX TO TWELVE scores were tested in the same statistical model, results confirmed a better AFP-DIAM performance.

The AFP-DIAM is an easy-to-use score which allows to distinguish two groups with different prognosis before the first TACE session. Its use could provide further support to BCLC system to guide the therapeutic strategy of patients with HCC.

With the rising incidence of hepatocellular carcinoma, there has been increasing use of local-regional therapy (LRT) to downstage or bridge to transplant, for definitive treatment, and for palliation. The CT/MRI Liver Imaging Reporting and Data System (LI-RADS) Treatment Response Assessment (TRA) algorithm provides guidance for step-by-step tumor assessment after LRT and standardized reporting. Current evidence suggests that the algorithm performs well in the assessment of tumor response to arterial embolic and loco-ablative therapies and fair when assessing response to radiation-based therapies, with limited data to validate the latter. Both evidence-based and expert-based refinements of the algorithm are needed to improve its diagnostic accuracy after varying types of LRT. This review provides an overview of the challenges and limitations of the LI-RADS TRA algorithm version 2017 and discusses the refinements introduced in the updated 2024 LI-RADS algorithm for CT/MRI.

Recent studies have highlighted that TACE in conjunction with Lenvatinib (TACE-L) offers a promising adjunct therapy for advanced HCC patients, outperforming TACE plus Sorafenib (TACE-S). However, there has been a lack of research comparing these two regimens for intermediate HCC.

This study aims to address the research gap by evaluating the efficacy of TACE-L versus TACE-S in intermediate HCC patients.

A retrospective analysis was conducted on a cohort of consecutive intermediate HCC patients who received either TACE-L or TACE-S from November 2018 to December 2022. Portal vein width was assessed using abdominal NMRI or Doppler ultrasonography, and inflammatory markers were derived from routine blood counts. The primary outcomes of interest were overall survival (OS), progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and adverse drug reactions (ADRs).

The study included 117 patients, with 56 in the TACE-S group and 61 in the TACE-L group. The TACE-S group demonstrated superior OS (HR = 1.704, 95% CI: 1.012-2.870, p = 0.045) compared to the TACE-L group. No significant difference was observed in PFS (HR:1.512, 95% CI: 0.988-2.313, p = 0.057) between the two groups. Subgroup analyses revealed that male patients, those with cirrhosis, and those with more than four tumors had better OS and PFS in the TACE-S group than in the TACE-L group. Inflammatory markers were comparable between the groups. The TACE-S group experienced a higher incidence of palmar-plantar erythrodysesthesia syndrome (PPE) (14/56 [25%] vs. 5/61 [8.1%], p = 0.014) but a lower incidence of hypertension (3/56 [5.3%] vs. 11/61 [18%], p = 0.035) compared to the TACE-L group.

In patients with intermediate HCC, TACE-S was found to be more effective in terms of OS than TACE-L. No significant disparity was noted in PFS between the two treatment groups.

Background/Objectives: The formula Chong-Lou-Yao-Fang (CLYF) is an herbal medicinal formulation developed by the indigenous Naxi people for treating liver cancer. This study was to reveal the biological activity, potential targets, and molecular mechanisms of CLYF for cancer treatment. Methods: Network pharmacology, microarray data analysis, survival analysis, and molecular docking were employed to predict potential compounds, targets, and pathways for the treatment of liver cancer. In vitro experiments and Western blot validation were conducted to confirm these predictions. Results: 35 key compounds and 20 core targets were screened from CLYF, involving signaling pathways for PI3K-Akt, MAPK, hepatitis B and C, which were effective for liver cancer treatment. Microarray data analysis and survival analysis indicated that EGFR and TP53 serve as promising biomarkers for diagnosis and prognosis in liver cancer. Molecular docking revealed stable binding between EGFR, TP53, and AKT1 with active ingredients. Cell experiments confirmed that CLYF-A suppressed cell proliferation, induced apoptosis, and caused cell cycle arrest in HepG2 cells, which were associated with a loss of mitochondrial membrane potential. Compared to the control group, the relative protein expression levels of EGFR and AKT1 significantly decreased following treatment with CLYF-A, while TP53 levels increased significantly. Conclusions: Verification of the anticancer activity of CLYF and its potential mechanisms may have important implications for anticancer therapies. Our results may provide a scientific basis for the clinical use of CLYF for cancer treatment and have important implications for developing pharmaceutical preparations, which also need more pharmacological experiments, clinical experiments, and in vivo experiments.

Hepatocellular carcinoma (HCC) represents a significant global health problem, requiring precise prognostic tools for optimal treatment stratification. This study aimed to develop a new risk prediction score, called AD score, based on the serum markers alpha-fetoprotein (AFP) and des-γ-carboxy prothrombin (DCP), to offer an objective and accurate preoperative assessment of HCC in patients undergoing transarterial chemoembolization (TACE).

This was a retrospective study that included 295 HCC patients who were subjected to TACE (training set, n=147; testing set, n=148). Serum AFP and DCP levels were log-transformed to construct the AD score. Multivariate Cox regression analysis on cirrhosis subgroups validated the objectivity of the model. Performance comparison of established models (Child Pugh, BCLC, ALBI, Up-to-seven, Six-and-twelve, Four and seven, HAP score, mHAP-II, FAIL-T score), was assessed through time-dependent receiver operating characteristic (ROC) curves and risk stratification.

The AD score, incorporating lgAFP and lgDCP, demonstrated superior predictive accuracy than the existing models. Time-dependent ROC curve revealed the consistent superiority of the AD score over a 5-year period. The risk stratification into low, intermediate, and high group based on the AD score showed a significant survival difference in both training and testing set.

For HCC patients undergoing TACE, the AD score serves as an objective and straightforward prognostic tool, enhancing predictive accuracy and showcasing its clinical utility. It demonstrates potential significance as a crucial addition to preoperative risk assessment for TACE.

Accumulating evidence suggests that certain imaging features of hepatocellular carcinoma (HCC) may have prognostic implications. This study aimed to intraindividually compare MRIs with extracellular contrast agent (ECA-MRI) and hepatobiliary agent (HBA-MRI) for prognostic imaging features of HCC and to compare the prediction of microvascular invasion (MVI) and early recurrence between the two MRIs.

The present study included 102 prospectively enrolled at-risk patients (median age, 61.0 years; 83 men) with surgically resected single HCC with both preoperative ECA-MRI and HBA-MRI between July 2019 and June 2023. The McNemar test was used to compare each prognostic imaging feature between the two MRIs. Significant imaging features associated with MVI were identified by multivariable logistic regression analysis, and early recurrence rates (<2 years) were compared between the two MRIs.

The frequencies of prognostic imaging features were not significantly different between the two MRIs (p = .07 to >.99). Non-smooth tumour margin (ECA-MRI, odds ratio [OR] = 5.30; HBA-MRI, OR = 7.07) and peritumoral arterial phase hyperenhancement (ECA-MRI, OR = 4.26; HBA-MRI, OR = 4.43) were independent factors significantly associated with MVI on both MRIs. Two-trait predictor of venous invasion (presence of internal arteries and absence of hypoattenuating halo) on ECA-MRI (OR = 11.24) and peritumoral HBP hypointensity on HBA-MRI (OR = 20.42) were other predictors of MVI. Early recurrence rates of any two or more significant imaging features (49.8% on ECA-MRI vs 51.3% on HBA-MRI, p = .75) were not significantly different between the two MRIs.

Prognostic imaging features of HCC may be comparable between ECA-MRI and HBA-MRI.

Although escalated doses of radiation therapy (RT) for intrahepatic cholangiocarcinoma (iCCA) are associated with durable local control (LC) and prolonged survival, uncertainties persist regarding personalized RT based on biological factors. Compounding this knowledge gap, the assessment of RT response using traditional size-based criteria via computed tomography (CT) imaging correlates poorly with outcomes. We hypothesized that quantitative measures of enhancement would more accurately predict clinical outcomes than size-based assessment alone and developed a model to optimize RT.

Pre-RT and post-RT CT scans of 154 patients with iCCA were analyzed retrospectively for measurements of tumor dimensions (for RECIST) and viable tumor volume using quantitative European Association for Study of Liver (qEASL) measurements. Binary classification and survival analyses were performed to evaluate the ability of qEASL to predict treatment outcomes, and mathematical modeling was performed to identify the mechanistic determinants of treatment outcomes and to predict optimal RT protocols.

Multivariable analysis accounting for traditional prognostic covariates revealed that percentage change in viable volume following RT was significantly associated with OS, outperforming stratification by RECIST. Binary classification identified ≥33% decrease in viable volume to optimally correspond to response to RT. The model-derived, patient-specific tumor enhancement growth rate emerged as the dominant mechanistic determinant of treatment outcome and yielded high accuracy of patient stratification (80.5%), strongly correlating with the qEASL-based classifier.

Following RT for iCCA, changes in viable volume outperformed radiographic size-based assessment using RECIST for OS prediction. CT-derived tumor-specific mathematical parameters may help optimize RT for resistant tumors.

Ultrasound (US) is recommended for HCC surveillance in high-risk patients but has limited performance in detecting early-stage HCC. We aimed to compare the diagnostic performance of biannual US and annual non-contrast abbreviated magnetic resonance imaging (NC-AMRI) as HCC surveillance modalities in high-risk patients.

This prospective, multicenter cohort study enrolled participants with an estimated annual risk of HCC greater than 5% between October 2015 and April 2017. Participants underwent six rounds of HCC surveillance at 6-month intervals, with both US and NC-AMRI at rounds 1, 3, and 5, and only US at rounds 2, 4, and 6. The sensitivity, diagnostic yield (DY), and false referral rate (FRR) for HCC detection by US and NC-AMRI were compared.

In total, 208 participants underwent 980 US and 516 NC-AMRI examinations during 30 months of follow-up. Among them, 34 HCCs were diagnosed in 31 participants, with 20 (64.5%) classified as very early-stage and 11 (35.5%) as early-stage HCC. The sensitivity of annual NC-AMRI (71.0%, 22/31) was marginally higher than that of biannual US (45.2%, 14/31; p = 0.077). NC-AMRI showed a significantly higher DY than US (4.26% vs. 1.43%, p <0.001), with a similar FRR (2.91% vs. 3.06%, p = 0.885). A simulation of alternating US and NC-AMRI at 6-month intervals yielded a sensitivity of 83.9% (26/31), significantly exceeding that of biannual US (p = 0.006).

Annual NC-AMRI showed a marginally higher sensitivity than biannual US for HCC detection in high-risk patients. The DY of annual NC-AMRI was significantly higher than that of biannual US, without increasing the FRR. Thus, alternating US and NC-AMRI at 6-month intervals could be an optimal surveillance strategy for high-risk patients.

Current guidelines permit the use of magnetic resonance imaging (MRI) as a surveillance tool for hepatocellular carcinoma in patients in whom ultrasonography (US) is inadequate. However, the specific indications, imaging sequences, and intervals for MRI surveillance remain unclear. In our study, we found that annual non-contrast abbreviated MRI exhibited marginally higher sensitivity and significantly better diagnostic yield than biannual US in patients at high risk of hepatocellular carcinoma. Alternating US and non-contrast abbreviated MRI at 6-month intervals led to significantly improved sensitivity compared to biannual US, making it a potentially optimal surveillance strategy for high-risk patients.

NCT02551250.

In many Asian hepatocellular carcinoma (HCC) guidelines, resection is an option for multiple HCCs. It is difficult to compare small but multiple tumors vs. fewer large tumors in terms of the traditional tumor burden definition. We aimed to evaluate the role of liver resection for multiple HCCs and determine factors associated with survival benefits.

We reviewed 160 patients with multiple HCCs who underwent liver resection between July 2003 and December 2018. The risk factors for tumor recurrence were assessed using Cox proportional hazards modeling, and survival was analyzed using the Kaplan-Meier method.

In all 160 patients, 133 (83.1%) exceeded the Milan criteria. Total tumor volume (TTV) > 275 cm3 and serum alpha-fetoprotein (AFP) level > 20 ng/mL were associated with disease-free survival. Patients beyond the Milan criteria were grouped into three risk categories: no risk (TTV ≤ 275 cm3 and AFP ≤ 20 ng/mL, n = 39), one risk (either TTV > 275 cm3 or AFP > 20 ng/mL, n = 76), and two risks (TTV > 275 cm3 and AFP > 20 ng/mL, n = 18). No-risk group had comparable disease-free survival (p = 0.269) and overall survival (p = 0.215) to patients who met the Milan criteria.

Patients with TTV ≤ 275 cm3 and AFP ≤ 20 ng/mL can have good outcomes even exceed the Milan criteria.

It is not known if the nature, number and duration of presenting symptoms at diagnosis of hepatocellular carcinoma impact on overall survival. This study examines whether the presenting symptoms of hepatocellular carcinoma have a significant impact on prognosis.

The study cohort comprised 725 patients with symptomatic hepatocellular carcinoma seen in our department since October 1983. Another 545 patients were diagnosed on surveillance or from incidental findings. Presenting symptoms at diagnosis were documented. A survival census was performed on 31 October 2015 with the national registry of deaths. Presenting symptoms were examined for association with overall survival using multivariable Cox regression analysis. Survival analysis was done by Kaplan-Meier method with log-rank testing. Bivariate Pearson correlation was used to look for any association between duration of symptoms and overall survival.

Patients with symptomatic hepatocellular carcinoma had a significantly shorter survival than those diagnosed incidentally or on screening (94.0 vs. 786.0 days, P < 0.001). Survival was shorter in patients presenting with fluid retention (56.0 vs. 118.0 days, P < 0.001), jaundice (48.0 vs. 94.0 days, P = 0.017) and two or more symptoms ( P = 0.010). Pain was associated with better survival ( P < 0.001). On multivariable Cox regression analysis, only fluid retention (hazard ratio [HR] 1.56, 95% confidence interval [CI] 1.30-1.87) and jaundice (HR 1.36, 95% CI 1.07-1.74) were independently associated with shorter survival. There was no significant relationship between the duration of symptoms and overall survival.

Patients with hepatocellular carcinoma who present with fluid retention or jaundice have significantly shorter overall survival. This is useful in assessing patients at the time of diagnosis.

This editorial comments on the study by Ma et al, which delves into the efficacy and predictive factors associated with the combination of transarterial chemoembolization, lenvatinib, and programmed cell death protein-1 inhibition for the management of unresectable hepatocellular carcinoma. Analysing data from a retrospective study involving 102 patients, the treatment showcased a median overall survival (OS) of 26.43 months and a median progression-free survival (PFS) of 10.07 months. Notably, the objective response rate and disease control rate reached 61.76% and 81.37%, respectively. Specific factors such as Barcelona Clinic Liver Cancer (BCLC) Classification B-stage, early neutrophil-to-lymphocyte ratio response, and early alpha-fetoprotein response (> 20% decrease) correlated with superior OS and PFS. The triple therapy exhibited promising efficacy, particularly in BCLC B-stage disease, with prognostic markers aiding in patient stratification. Acknowledging the retrospective nature of the study design, future research should address this limitation and incorporate longer follow-up periods for a comprehensive evaluation of long-term outcomes.

Focal liver lesions (FLLs) have become an increasingly common finding on abdominal imaging, especially asymptomatic and incidental liver lesions. Gastroenterologists and hepatologists often see these patients in consultation and make recommendations for management of multiple types of liver lesions, including hepatocellular adenoma, focal nodular hyperplasia, hemangioma, and hepatic cystic lesions including polycystic liver disease. Malignancy is important to consider in the differential diagnosis of FLLs, and healthcare providers must be familiar with the diagnosis and management of FLLs. This American College of Gastroenterology practice guideline uses the best evidence available to make diagnosis and management recommendations for the most common FLLs.

The risk of developing HCC in chronically infected patients with AQ2 HCV with liver cirrhosis is significantly elevated. This risk remains high even after a sustained virological response with direct-acting antivirals. To date, disease-associated signatures of NK cells indicating HCC development are unclear.

This study investigated NK cell signatures and functions in 8 cohorts covering the time span of HCC development, diagnosis, and onset. In-depth analysis of NK cell profiles from patients with cirrhosis who developed HCC (HCV-HCC) after sustained virological response compared with those who remained tumor-free (HCV-noHCC) revealed increasingly dissimilar NK cell signatures over time. We identified expression patterns with persistently high frequencies of TIM-3 and CD38 on NK cells that were largely absent in healthy controls and were associated with a high probability of HCC development. Functional assays revealed that the NK cells had potent cytotoxic features. In contrast to HCV-HCC, the signature of HCV-noHCC converged with the signature found in healthy controls over time. Regarding tissue distribution, single-cell sequencing showed high frequencies of these cells in liver tissue and the invasive margin but markedly lower frequencies in tumors.

We show that HCV-related HCC development has profound effects on the imprint of NK cells. Persistent co-expression of TIM-3hi and CD38 + on NK cells is an early indicator for HCV-related HCC development. We propose that the profiling of NK cells may be a rapid and valuable tool to assess the risk of HCC development in a timely manner in patients with cirrhosis after HCV cure.

Hepatocellular carcinoma (HCC) is a primary malignant tumor of liver epithelial cells and is the most frequent primary liver cancer. The broadening of transplantation and resectability criteria has made therapeutic decisions more complex. Our aim was to describe the clinical and survival characteristics of patients with HCC treated through resection or liver transplantation at our hospital and identify the presence of factors that enable outcome prediction and facilitate therapeutic decision-making.

Patients with HCC that underwent surgery with curative intent at the Hospital Universitario Marqués de Valdecilla, within the time frame of 2007 and 2017, were retrospectively identified. Survival, mortality, disease-free interval, and different outcome-related variables were analyzed.

Ninety-six patients with a mean follow-up after surgery of 44 months were included. Overall mortality and recurrence were higher in the resection group. Mean survival was 51.4 months in the liver transplantation group and 37.5 months in the resection group, and the disease-free interval was 49.4 ± 37.2 and 27.4 ± 28.7 months, respectively (p = 0.002). The tumor burden score was statistically significant regarding risk for recurrence and specific mortality.

There appears to be no patient subgroup in whom the results of surgical resection were superior or comparable to those of transplantation. Tumor burden determination could be a useful tool for patient subclassification and help guide therapeutic decision-making.

Clinically significant portal hypertension (CSPH) seriously affects the feasibility and safety of surgical treatment for hepatocellular carcinoma (HCC) patients. The aim of this study was to establish a new surgical scheme defining risk classification of post-hepatectomy liver failure (PHLF) to facilitate the surgical decision-making and identify suitable candidates for individual hepatectomy among HCC patients with CSPH.

Hepatectomy is the preferred treatment for HCC. Surgeons must maintain a balance between the expected oncological outcomes of HCC removal and short-term risks of severe PHLF and morbidity. CSPH aggravates liver decompensation and increases the risk of severe PHLF thus complicating hepatectomy for HCC.

Multivariate logistic regression and stochastic forest algorithm were performed, then the independent risk factors of severe PHLF were included in a nomogram to determine the risk of severe PHLF. Further, a conditional inference tree (CTREE) through recursive partitioning analysis validated supplement the misdiagnostic threshold of the nomogram.

This study included 924 patients, of whom 137 patients (14.8%) suffered from mild-CSPH and 66 patients suffered from (7.1%) with severe-CSPH confirmed preoperatively. Our data showed that preoperative prolonged prothrombin time, total bilirubin, indocyanine green retention rate at 15 min, CSPH grade, and standard future liver remnant volume were independent predictors of severe PHLF. By incorporating these factors, the nomogram achieved good prediction performance in assessing severe PHLF risk, and its concordance statistic was 0.891, 0.850 and 0.872 in the training cohort, internal validation cohort and external validation cohort, respectively, and good calibration curves were obtained. Moreover, the calculations of total points of diagnostic errors with 95% CI were concentrated in 110.5 (range 76.9-178.5). It showed a low risk of severe PHLF (2.3%), indicating hepatectomy is feasible when the points fall below 76.9, while the risk of severe PHLF is extremely high (93.8%) and hepatectomy should be rigorously restricted at scores over 178.5. Patients with points within the misdiagnosis threshold were further examined using CTREE according to a hierarchic order of factors represented by the presence of CSPH grade, ICG-R15, and sFLR.

This new surgical scheme established in our study is practical to stratify risk classification in assessing severe PHLF, thereby facilitating surgical decision-making and identifying suitable candidates for individual hepatectomy.

Although radical surgical resection is the most effective treatment for hepatocellular carcinoma (HCC), the high rate of postoperative recurrence remains a major challenge, especially in patients with alpha-fetoprotein (AFP)-negative HCC who lack effective biomarkers for postoperative recurrence surveillance. Emerging radiomics can reveal subtle structural changes in tumors by analyzing preoperative contrast-enhanced computer tomography (CECT) imaging data and may provide new ways to predict early recurrence (recurrence within 2 years) in AFP-negative HCC. In this study, we propose to develop a radiomics model based on preoperative CECT to predict the risk of early recurrence after surgery in AFP-negative HCC.

Patients with AFP-negative HCC who underwent radical resection were included in this study. A computerized tool was used to extract radiomic features from the tumor region of interest (ROI), select the best radiographic features associated with patient's postoperative recurrence, and use them to construct the radiomics score (RadScore), which was then combined with clinical and follow-up information to comprehensively evaluate the reliability of the model.

A total of 148 patients with AFP-negative HCC were enrolled in this study, and 1,977 radiographic features were extracted from CECT, 2 of which were the features most associated with recurrence in AFP-negative HCC. They had good predictive ability in both the training and validation cohorts, with an area under the ROC curve (AUC) of 0.709 and 0.764, respectively. Tumor number, microvascular invasion (MVI), AGPR and radiomic features were independent risk factors for early postoperative recurrence in patients with AFP-negative HCC. The AUCs of the integrated model in the training and validation cohorts were 0.793 and 0.791, respectively. The integrated model possessed the clinical value of predicting early postoperative recurrence in patients with AFP-negative HCC according to decision curve analysis, which allowed the classification of patients into subgroups of high-risk and low-risk for early recurrence.

The nomogram constructed by combining clinical and imaging features has favorable performance in predicting the probability of early postoperative recurrence in AFP-negative HCC patients, which can help optimize the therapeutic decision-making and prognostic assessment of AFP-negative HCC patients.