Liver cancer is a global health challenge, causing a significant social-economic burden. Hepatocellular carcinoma (HCC) is the predominant type of primary liver cancer, which is highly heterogeneous in terms of molecular and cellular signatures. Early-stage or small tumors are typically treated with surgery or ablation. Currently, chemotherapies and immunotherapies are the best treatments for unresectable tumors or advanced HCC. However, drug response and acquired resistance are not predictable with the existing systematic guidelines regarding mutation patterns and molecular biomarkers, resulting in sub-optimal treatment outcomes for many patients with atypical molecular profiles. With advanced technological platforms, valuable information such as tumor genetic alterations, epigenetic data, and tumor microenvironments can be obtained from liquid biopsy. The inter- and intra-tumoral heterogeneity of HCC are illustrated, and these collective data provide solid evidence in the decision-making process of treatment regimens. This article reviews the current understanding of HCC detection methods and aims to update the development of HCC surveillance using liquid biopsy. Recent critical findings on the molecular basis, epigenetic profiles, circulating tumor cells, circulating DNAs, and omics studies are elaborated for HCC diagnosis. Besides, biomarkers related to the choice of therapeutic options are discussed. Some notable recent clinical trials working on targeted therapies are also highlighted. Insights are provided to translate the knowledge into potential biomarkers for detection and diagnosis, prognosis, treatment response, and drug resistance indicators in clinical practice.

UNASSIGNED: This study aimed to investigate the feasibility of the efficacy and safety of TACE combined with Lenvatinib and PD-1 blockade in HCC with portal vein tumor thrombus (PVTT).
UNASSIGNED: Patients with HCC and PVTT who underwent TACE combined with Lenvatinib and PD-1 blockade as first-line therapy in clinical practice were retrospectively included. All subjects were followed-up regularly to obtain prognostic outcomes. The safety profile observed during the combination therapy was collected and documented. The Log rank test was used for exploratory analysis of prognosis and baseline characteristics and Cox regression analysis was used for multivariate analysis.
UNASSIGNED: A total of 67 HCC patients with PVTT who received TACE combined with Lenvatinib and PD-1 blockade were included in this study. The best therapeutic response during treatment suggested that 4 patients achieved complete response, 30 patients showed partial response, 25 patients were stable disease, 5 patients had disease progression and 3 patients were not available. Objective response rate of this regimen was 50.7% [95% confidence interval (CI): 38.2-63.2%] and disease control rate was 88.1% (95% CI: 77.8-94.7%). The median progression-free survival of 67 HCC patients with PVTT who received TACE combined with Lenvatinib and PD-1 blockades was 9.3 months (95% CI: 5.85-12.75), and the median overall survival was 24.4 months (95% CI: 19.11-29.69). The safety profile highlighted that 65 patients experienced adverse reactions regardless of grade during treatment (97.0%), among whom 34 patients were deemed as grade ≥3 adverse reactions (50.7%). The most common adverse reactions were hypertension, fatigue, abnormal liver function, nausea, vomiting, and diarrhea. Overall adverse reactions were acceptable and controllable.
UNASSIGNED: TACE combined with Lenvatinib and PD-1 blockades as first-line therapy for HCC with PVTT demonstrated potential feasibility and encouraging clinical outcomes, providing long-term survival benefits for HCC patients. This conclusion should be confirmed in prospective large-scale clinical trials.

UNASSIGNED: Hepatectomy could provide better survival benefit for hepatocellular carcinoma (HCC) with type I/II portal vein tumor thrombosis (PVTT). However, the postoperative recurrence remains high. We discussed whether neoadjuvant therapy could reduce HCC recurrence for these patients.
UNASSIGNED: One hundred and thirty-eight resectable HCC with type I-II PVTT were retrospectively included. The neoadjuvant therapy regimens included tyrosine kinase inhibitor (TKI), programmed death 1(PD-1) antibodies and transarterial chemoembolization (TACE). Short-term and long-term outcomes were compared. Propensity score matching (PSM) was performed to minimize the influence of potential confounders.
UNASSIGNED: Thirty-three patients underwent neoadjuvant therapy and 105 patients underwent surgery alone. In the neoadjuvant group, 7 (21.2%) patients achieved stable disease, 13 (39.4%) achieved partial response and 13 (39.4%) achieved complete response based on the modified Response Evaluation Criteria in Solid Tumors criterion. By PSM, the neoadjuvant therapy resulted in less microvascular invasion (24.1% vs 50.0%, P=0.021), satellite nodule (6.9% vs 24.1%, P=0.036) and less patients with alpha-fetoprotein>20(ng/mL) (37.9% vs 69.0%, P=0.006). The neoadjuvant therapy reduced tumor recurrence and prolonged survival. Multivariate analysis found that neoadjuvant therapy was an independent protective factor for overall survival and recurrence free survival.
UNASSIGNED: Neoadjuvant treatment presents a promising treatment option for HCC patients with type I/II PVTT.

UNASSIGNED: The aim of this study was to report the safety and tumor response rate of combined transarterial radioembolization (TARE) through the intrahepatic arteries and transarterial chemoembolization (TACE) through the extrahepatic feeding arteries (EHFA) in patients with hepatocellular carcinoma (HCC).
UNASSIGNED: Patients with HCC, who had both intrahepatic and extrahepatic arterial supply visible on preinterventional multiphase CT and were treated between 2016 and 2021 with a combination of TACE and TARE on the same nodule, were retrospectively included. Epidemiological, clinical, biological, and radiological characteristics were recorded. Safety and tumor response were assessed at 6 months.
UNASSIGNED: Nine patients (8 men, median age 62 years [IQR: 54-72 years]) were included. Seven patients had previous treatments on the target nodule (TARE: 5; TACE: 2). The median longest axis (LA) of the lesion was 70 mm (IQR: 60-79 mm). Three patients had portal vein invasion (VP3). The EHFA originated from the right diaphragmatic artery (n = 6), the right adrenal artery (n = 2), and the left gastric artery (n = 1). The LA of the tumor portion treated with TACE was 47 mm (range: 35-64 mm). The ratio between the LA of the entire lesion and the LA treated with TACE was 1.44 (range: 1.27-1.7). One major complication occurred: acute on chronic liver failure. Median follow-up was 23 months (range: 16-29 months). Seven patients underwent further treatment: on the same lesion (n = 2), on newly appeared nodules (n = 2), and systemic treatment (n = 3). At 6-month follow-up, seven patients showed a local objective response. Time-to-progression was 13 (3.5-19) months.
UNASSIGNED: The combination of TARE and extrahepatic TACE for HCC with both intrahepatic and extrahepatic arterial supplies seems feasible and safe. Further studies are needed to validate the effectiveness of these preliminary results.

OBJECTIVE: The Japanese Interventional oncology group (JIVROSG) showed the efficacy and safety of nonselective transarterial chemoembolization (TACE) with fine cisplatin powder (diamminedichloroplatinum; DDP-H) (65 mg/m2) and porous gelatin particles (DDP-H TACE) without lipiodol for extensive multifocal hepatocellular carcinoma (HCC). However, there are no studies on this method following the JIVROSG study. Therefore, we aimed to evaluate the efficacy of this new DDP-H TACE and its effect on liver function.
METHODS: We retrospectively reviewed the medical records of TACE-naïve patients with multifocal HCC (Child-Pugh class A, up-to-seven out, no prior history of systemic therapy) who underwent whole-liver DDP-H TACE between January 2006 and December 2019.
RESULTS: Sixty patients were included in this study. The median age of the patients was 71 (range, 35-88) years. The median maximum size of tumors was 26 (range, 8-184) mm; 86.7% of patients met the up-to-11 criteria out. The overall survival duration was 30.3 months. At the time of initial evaluation (median, 45 days), the overall response rate was 65.0%; the disease control rate was 86.7% based on the modified response evaluation criteria in solid tumors guideline. Although nine patients\' liver function had deteriorated to Child-Pugh class B at initial evaluation, six of them recovered to Child-Pugh class A. Only three patients (5%) showed permanently impaired liver function.
CONCLUSIONS: Whole-liver DDP-H TACE without lipiodol or beads effectively reduced tumors and preserved liver function.

The present standard of care for unresectable liver cancer is transarterial chemoembolization (TACE), which involves using chemotherapeutic particles to selectively embolize the arteries supplying hepatic tumors. Accurate volumetric identification of intricate fine vascularity is crucial for selective embolization. Three-dimensional imaging, particularly cone-beam CT (CBCT), aids in visualization and targeting of small vessels in such highly variable anatomy, but long image acquisition time results in intra-scan patient motion, which distorts vascular structures and tissue boundaries. To improve clarity of vascular anatomy and intra-procedural utility, this work proposes a targeted motion estimation and compensation framework that removes the need for any prior information or external tracking and for user interaction. Motion estimation is performed in two stages: (i) a target identification stage that segments arteries and catheters in the projection domain using a multi-view convolutional neural network to construct a coarse 3D vascular mask; and (ii) a targeted motion estimation stage that iteratively solves for the time-varying motion field via optimization of a vessel-enhancing objective function computed over the target vascular mask. The vessel-enhancing objective is derived through eigenvalues of the local image Hessian to emphasize bright tubular structures. Motion compensation is achieved via spatial transformer operators that apply time-dependent deformations to partial angle reconstructions, allowing efficient minimization via gradient backpropagation. The framework was trained and evaluated in anatomically realistic simulated motion-corrupted CBCTs mimicking TACE of hepatic tumors, at intermediate (3.0 mm) and large (6.0 mm) motion magnitudes. Motion compensation substantially improved median vascular DICE score (from 0.30 to 0.59 for large motion), image SSIM (from 0.77 to 0.93 for large motion), and vessel sharpness (0.189 mm-1 to 0.233 mm-1 for large motion) in simulated cases. Motion compensation also demonstrated increased vessel sharpness (0.188 mm-1 before to 0.205 mm-1 after) and reconstructed vessel length (median increased from 37.37 to 41.00 mm) on a clinical interventional CBCT. The proposed anatomy-aware motion compensation framework presented a promising approach for improving the utility of CBCT for intra-procedural vascular imaging, facilitating selective embolization procedures.

BACKGROUND: The CRAFITY score serves as a simple and effective predictive model for individuals diagnosed with hepatocellular carcinoma (HCC) and subjected to treatment with atezolizumab and bevacizumab (Atez/Bev). However, no large sample size studies have reported the application of the CRAFITY score among HCC patients undergoing transarterial chemoembolization (TACE) in conjunction with lenvatinib. This research aims to assess the prognostic role of the CRAFITY score in the context of individuals with HCC receiving TACE in combination with lenvatinib.
METHODS: This retrospective analysis encompassed 314 individuals diagnosed with HCC who underwent the combination of TACE and lenvatinib at two medical facilities in China from August 2019 to August 2022 (comprising a training cohort of n = 172 and a validation cohort of n = 142). We investigated the prognostic values of overall survival (OS), progression-free survival (PFS), disease control rate, and objective response rate in the training cohort based on the CRAFITY scores. Furthermore, the predictive capacity of the model was corroborated through validation using an external cohort.
RESULTS: We included 174 and 142 patients treated with TACE plus lenvatinib in the training and validation cohorts, correspondingly. PFS and OS differed across all three groups in all training and validation cohorts, based on the CRAFITY score (p < 0.001). In both cohorts, the CRAFITY score effectively predicted tumor response (p < 0.001). Moreover, among the 121 patients who received TACE, lenvatinib, and immunotherapy, the CRAFITY score showed promising predictive efficacy in PFS and OS.
CONCLUSIONS: The CRAFITY score, utilizing C-reactive protein and alpha-fetoprotein values, emerges as a dependable and pragmatic instrument for forecasting the effectiveness of TACE plus lenvatinib in individuals with unresectable HCC. This scoring system holds the potential to assist oncologists in making informed clinical decisions.

UNASSIGNED: We explored the role of tumor size and number in the prognosis of HCC patients who underwent ablation and created a nomogram based on machine learning to predict the recurrence.
UNASSIGNED: A total of 990 HCC patients who underwent transcatheter arterial chemoembolization (TACE) combined ablation at Beijing Youan Hospital from January 2014 to December 2021 were prospectively enrolled, including 478 patients with single small HCC (S-S), 209 patients with single large (≥30mm) HCC (S-L), 182 patients with multiple small HCC (M-S), and 121 patients with multiple large HCC (M-L). S-S patients were randomized in a 7:3 ratio into the training cohort (N=334) and the validation cohort (N=144). Lasso-Cox regression analysis was carried out to identify independent risk factors, which were used to construct a nomogram. The performance of the nomogram was evaluated by C-index, receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA) curves. Patients in the training and validation cohorts were divided into low-risk, intermediate-risk, and high-risk groups based on the risk scores of the nomogram.
UNASSIGNED: The median recurrence-free survival (mRFS) in S-S patients was significantly longer than the S-L, M-S, and S-L patients (P<0.0001). The content of the nomogram includes age, monocyte-to-lymphocyte (MLR), gamma-glutamyl transferase-to-lymphocyte (GLR), International normalized ratio (INR), and Erythrocyte (RBC). The C-index (0.704 and 0.71) and 1-, 3-, and 5-year AUCs (0.726, 0.800, 0.780, and 0.752, 0.761, 0.760) of the training and validation cohorts proved the excellent predictive performance of the nomogram. Calibration curves the DCA curves showed that the nomogram had good consistency and clinical utility. There were apparent variances in RFS between the low-risk, intermediate-risk, and high-risk groups (P<0.0001).
UNASSIGNED: S-S patients who underwent ablation had the best prognosis. The nomogram developed and validated in the study had good predictive ability for S-S patients.

BACKGROUND: Diagnosis of the majority of hepatocellular carcinoma (HCC) patients occurs at intermediate to advanced stages, with a few curative therapeutic options being available. It is therefore strongly urgent to discover additional adjuvant therapy for this lethal malignancy. This study aimed to assess the effectiveness of curcumin (C), piperine (P) and taurine (T) combination as adjuvant agents on serum levels of IFN-γ, immunophenotypic and molecular characterization of mononuclear leukocytes (MNLs) in HCC patients treated with Transarterial chemoembolization (TACE).
METHODS: Serum and MNLs were collected from 20 TACE-treated HCC patients before (baseline-control samples) and after treatment with 5 g curcumin capsules , 10 mg piperine and 0.5 mg taurine taken daily for three consecutive months. Immunophenotypic and molecular characterization of MNLs were determined by flow cytometry and quantitative real time PCR, respectively. In addition, serum IFN-γ level was quantified by ELISA.
RESULTS: After receiving treatment with CPT combination, there was a highly significant increase in IFN- γ levels in the sera of patients when compared to basal line control samples. Additionally, the group receiving combined therapy demonstrated a downregulation in the expression levels of PD-1, in MNLs as compared to controls. MNLs\' immunophenotyping revealed a significant decline in CD4+CD25+cells (regulatory T lymphocytes). Furthermore, clinicopathological characteristics revealed a highly significant impact of CPT combination on aspartate aminotransferase (AST), lactate dehydrogenase (LDH) and alpha feto protein (AFP) levels.
CONCLUSIONS: This study introduces a promising adjuvant CPT combined treatment as natural agents to enhance the management of HCC patients who are candidates to TACE treatment.

(1) Background: HBV-DNA is an essential clinical indicator of primary hepatocellular carcinoma (HCC) prognosis. Our study aimed to investigate the prognostic implication of a low load of HBV-DNA in HCC patients who underwent local treatment. Additionally, we developed and validated a nomogram to predict the recurrence of patients with low (20-100 IU/mL) viral loads (L-VL). (2) Methods: A total of 475 HBV-HCC patients were enrolled, including 403 L-VL patients and 72 patients with very low (<20 IU/mL) viral loads (VL-VL). L-VL HCC patients were randomly divided into a training set (N = 282) and a validation set (N = 121) at a ratio of 7:3. Utilizing the Lasso-Cox regression analysis, we identified independent risk factors for constructing a nomogram. (3) Results: L-VL patients had significantly shorter RFS than VL-VL patients (38.2 m vs. 23.4 m, p = 0.024). The content of the nomogram included gender, BCLC stage, Glob, and MLR. The C-index (0.682 vs. 0.609); 1-, 3-, and 5-year AUCs (0.729, 0.784, and 0.783, vs. 0.631, 0.634, the 0.665); calibration curves; and decision curve analysis (DCA) curves of the training and validation cohorts proved the excellent predictive performance of the nomogram. There was a statistically significant difference in RFS between the low-, immediate-, and high-risk groups both in the training and validation cohorts (p < 0.001); (4) Conclusions: Patients with L-VL had a worse prognosis. The nomogram developed and validated in this study has the advantage of predicting patients with L-VL.