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The proliferative nature of hepatocellular carcinoma (HCC) is closely related to early recurrence following radical resection. This study develops and validates a deep learning (DL) prediction model to distinguish between proliferative and non-proliferative HCCs using dynamic contrast-enhanced MRI (DCE-MRI), aiming to refine preoperative assessments and optimize treatment strategies by assessing early recurrence risk. In this retrospective study, 355 HCC patients from two Chinese medical centers (April 2018–February 2023) who underwent radical resection were included. Patient data were collected from medical records, imaging databases, and pathology reports. The cohort was divided into a training set (n = 251), an internal test set (n = 62), and external test sets (n = 42). A DL model was developed using DCE-MRI images of primary tumors. Clinical and radiological models were generated from their respective features, and fusion strategies were employed for combined model development. The discriminative abilities of the clinical, radiological, DL, and combined models were extensively analyzed. The performances of these models were evaluated against pathological diagnoses, with independent and fusion DL-based models validated for clinical utility in predicting early recurrence. The DL model, using DCE-MRI, outperformed clinical and radiological feature-based models in predicting proliferative HCC. The area under the curve (AUC) for the DL model was 0.98, 0.89, and 0.83 in the training, internal validation, and external validation sets, respectively. The AUCs for the combined DL and clinical feature models were 0.99, 0.86, and 0.83 in these sets, while the AUCs for the combined DL, clinical, and radiological model were 0.99, 0.87, and 0.8, respectively. Among models predicting early recurrence, the DL plus clinical features model showed superior performance. The DL-based DCE-MRI model demonstrated robust performance in predicting proliferative HCC and stratifying patient risk for early postoperative recurrence. As a non-invasive tool, it shows promise in enhancing decision-making for individualized HCC management strategies [ABSTRACT FROM AUTHOR]

This study aims to assess the efficacy and safety of CT-guided percutaneous cryoablation in treating hepatocellular carcinoma (HCC) located explicitly in high-risk sites. Data were collected retrospectively from 685 HCC patients undergoing percutaneous cryoablation at Tianjin Medical University Cancer Hospital between January 2018 and December 2021. Of these, 106 patients had lesions in high-risk sites, defined as a minimum distance of less than 10 mm from the heart/great vessels, diaphragm, gastrointestinal tract, and gallbladder, as determined by preoperative CT or MRI imaging. Technical success rate, complete ablation rate, and complications at 1, 12, and 24 months post-surgery were evaluated. A statistical analysis of the ablation effect difference between the high-risk site and non-high-risk site groups was conducted, utilizing propensity score matching (PSM) to mitigate patient selection bias. Univariate and multivariate logistic regression analyzes were performed to identify risk factors for the incidence of coronary heart disease. The study comprised 106 cases in the high-risk group and 218 cases in the non-high-risk group. After PSM analysis until December 2021, 95 matched pairs were included. Both groups demonstrated a 100% intraoperative technical success rate, and no major complications related to cryoablation were observed. Follow-up ranged from 24 to 38 months. The complete ablation rate was 82.1% and 71.7% in the high-risk group and 83.9% and 73.9% in the non-high-risk group at 12 and 24 months, respectively. There was no significant difference in complete ablation rates between the two groups before and after PSM (P > 0.05). Multivariate analysis identified the distance between the tumor edge and high-risk site ≤ 5 mm and preoperative transarterial chemoembolization (TACE) treatment as independent risk factors for cryoablation effect. CT-guided percutaneous cryoablation proves to be a safe and effective approach for HCC patients with high-risk sites, serving as an alternative to surgical treatment. [ABSTRACT FROM AUTHOR]

Risk stratification for patients with a higher risk of hepatocellular carcinoma (HCC) is crucial. We aimed to investigate the role of the Fibrosis-4 (FIB-4) index in predicting chronic hepatitis C (CHC)-related HCC. A retrospective cohort study consecutively included treatment-naive CHC patients receiving longitudinal follow-up at the National Taiwan University Hospital from 1986 to 2014. The clinical data were collected and traced for HCC development. Multivariable Cox proportional hazard regression analysis was used to investigate the predictors for HCC. A total of 1285 patients in the ERADICATE-C cohort were included. The median age was 54, 56% were females, and 933 had HCV viremia. There were 33%, 38%, and 29% of patients having FIB-4 index <1.45, 1.45–3.25, and ≥3.25, respectively. After a median of 9-year follow-up, 186 patients developed HCC. Multivariable analysis revealed that older age, AFP≥20 ng/mL, cirrhosis, and a higher FIB-4 index were independent predictors for HCC. Compared with patients with FIB-4 index <1.45, those with FIB-4 1.45–3.25 had a 5.51-fold risk (95% confidence interval [CI]: 2.65–11.46), and those with FIB-4 ≥ 3.25 had 7.45-fold risk (95% CI: 3.46–16.05) of HCC. In CHC patients without viremia, FIB-4 index 1.45–3.25 and FIB-4 ≥ 3.25 increased 6.78-fold and 16.77-fold risk of HCC, respectively, compared with those with FIB-4 < 1.45. The baseline FIB-4 index can stratify the risks of HCC in untreated CHC patients, even those without viremia. The FIB-4 index should thus be included in the management of CHC. [ABSTRACT FROM AUTHOR]

The advent of direct-acting antiviral (DAA) therapy has revolutionized hepatitis C virus (HCV) treatment, enabling most HCV-infected patients to achieve a sustained viral response (SVR) easily and safely in a short period. On the other hand, it is gradually being recognized that a significant proportion of patients are still at risk of developing de novo and recurrent hepatocellular carcinoma (HCC), even after HCV elimination, and therefore, elucidation of the risk of de novo and recurrent HCC, investigation of its molecular basis, and construction of accurate prediction models are emerging as new important clinical topics. In this review, we present recent advances regarding these issues. [ABSTRACT FROM AUTHOR]

Increasing evidence supports the connection between the progression of several cancers and BRK1. However, the clinical significance of aberrant BRK1 gene expression in cancer is unknown. This study is conducted to investigate the possibility and effect of BRK1 as a potential immunotherapy target, to deliver a better option for liver cancer immunotherapy. We explored the predictive role of BRK1 expression in a variety of cancers from different bioinformatics, including differential expression in different cancers, tumor microenvironment (TME), microsatellite instability (MSI), tumor mutational burden (TMB), immune checkpoint molecules, immune-related and cell cycle-related signalling pathways, and drug response sensitivity. Finally, we verified the expression of BRK1 in hepatocellular carcinoma using immunohistochemistry. BRK1 is overexpressed in multiple cancers and displays a negative association with prognosis and progression of disease in a wide range of main cancer types. Additionally, the expression of BRK1 is related to MSI and TMB of tumors. There was also a remarkable correlation between the expression of BRK1 and immune score, immune infiltration, immune checkpoint molecules and a stromal score of tumors. In hepatocellular carcinoma, BRK1 is associated with several signaling pathways and immune cell infiltration may affect several key immune-related regulatory genes, making it an excellent biomarker and may be a sensitive target for immune drugs.Our research suggests that BRK1 may be a potential prognostic marker and target for immunotherapy and may be associated with poor prognosis in diverse malignancies, including hepatocellular carcinoma. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) is identified as a common cancer type across the world and needs novel and efficient treatment. Tripterine, a well-known compound, exerts suppressive role in HCC development. However, the related molecular mechanism of tripterine in HCC remains unclear. The expression of MBNL1‐AS1in HCC tissues and cells was measured via qRT-PCR assay. MTT assay was employed to estimate cell viability. Besides, cell migration as well as invasion was determined through transwell assay. Additionally, the binding ability of miR-708-5p and MBNL1-AS1or HK2 was proved by starBase database and luciferase reporter gene assay. Moreover, the HK2 level was detected by immunoblotting. MBNL1-AS1 was reduced in HCC tissues and cells. Overexpression of MBNL1-AS1 decreased the sensitivity of HCC cells to tripterine while MBNL1-AS1 silence played opposite effect. In addition, miR-708-5p was the target of MBNL1-AS1 and was down-regulated through MBNL1-AS1 in HCC cells. Moreover, miR-708-5p suppressed glycolysis rate and reduced the expression of vital glycolytic enzyme (HK2, LDHA and PKM2) in HCC cells. Furthermore, miR-708-5p reduced HK2 expression by binding to it directly. In this investigation, we proved that LncRNA MBNL1-AS1 increased the tripterine resistance of HCC cells at least partly by mediating miR-708-5p-related glycolysis. These findings revealed a potent therapeutic target for the treatment of HCC. [ABSTRACT FROM AUTHOR]

In advanced hepatocellular carcinoma (HCC) tissues, M2-like tumor-associated macrophages (TAMs) are in the majority and promotes HCC progression. Contrary to the pro-tumor effect of M2-like TAMs, M1-like TAMs account for a small proportion and have anti-tumor effects. Since TAMs can switch from one type to another, reprogramming TAMs may be an important treatment for HCC therapy. However, the mechanisms of phenotypic switch and reprogramming TAMs are still obscure. In this study, we analyzed differential genes in normal macrophages and TAMs, and found that loss of MANF in TAMs accompanied by high levels of downstream genes negatively regulated by MANF. MANF reprogrammed TAMs into M1 phenotype. Meanwhile, loss of MANF promoted HCC progression in HCC patients and mice HCC model, especially tumor neovascularization. Additionally, macrophages with MANF supplement suppressed HCC progression in mice, suggesting MANF supplement in macrophage was an effective treatment for HCC. Mechanistically, MANF enhanced the HSF1–HSP70-1 interaction, restricted HSF1 in the cytoplasm of macrophages, and decreased both mRNA and protein levels of HSP70-1, which in turn led to reprogramming TAMs, and suppressing neovascularization of HCC. Our study contributes to the exploration the mechanism of TAMs reprogramming, which may provide insights for future therapeutic exploitation of HCC neovascularization. MANF enhances the interaction of HSF1 and HSP70-1, which in turn inhibits HSF1 nuclear import and decreases HSP70-1 transcription, leading to the reprogramming of TAMs and further inhibition of HCC neovascularization. [Display omitted] [ABSTRACT FROM AUTHOR]

Transarterial chemoembolization (TACE) plus molecular targeted therapies has emerged as the main approach for treating hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT). A robust model for outcome prediction and risk stratification of recommended TACE plus molecular targeted therapies candidates is lacking. We aimed to develop an easy-to-use tool specifically for these patients. A retrospective analysis was conducted on 384 patients with HCC and PVTT who underwent TACE plus molecular targeted therapies at 16 different institutions. We developed and validated a new prognostic score which called ABPS score. Additionally, an external validation was performed on data from 200 patients enrolled in a prospective cohort study. The ABPS score (ranging from 0 to 3 scores), which involves only Albumin-bilirubin (ALBI, grade 1: 0 score; grade 2: 1 score), PVTT(I–II type: 0 score; III–IV type: 1 score), and systemic-immune inflammation index (SII,<550 × 1012: 0 score; ≥ 550 × 1012: 1 score). Patients were categorized into three risk groups based on their ABPS score: ABPS-A, B, and C (scored 0, 1–2, and 3, respectively). The concordance index (C-index) of the ABPS scoring system was calculated to be 0.802, significantly outperforming the HAP score (0.758), 6–12 (0.712), Up to 7 (0.683), and ALBI (0.595) scoring systems (all P < 0.05). These research findings were further validated in the external validation cohorts. The ABPS score demonstrated a strong association with survival outcomes and radiological response in patients undergoing TACE plus molecular targeted therapy for HCC with PVTT. The ABPS scoring system could serve as a valuable tool to guide treatment selection for these patients. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) is an inflammatory cancer. We aimed to explore whether preoperative inflammation biomarkers compared to the gadoxetic acid disodium (Gd-EOB-DTPA) enhanced MRI can add complementary value for predicting HCC pathological grade, and to develop a dynamic nomogram to predict solitary HCC pathological grade. 331 patients from the Institution A were divided chronologically into the training cohort (n = 231) and internal validation cohort (n = 100), and recurrence-free survival (RFS) was determined to follow up after surgery. 79 patients from the Institution B served as the external validation cohort. Overall, 410 patients were analyzed as the complete dataset cohort. Least absolute shrinkage and selection operator (LASSO) and multivariate Logistic regression were used to gradually filter features for model construction. The area under the receiver operating characteristic curve (AUC) and decision curve analysis were used to evaluate model's performance. Five models of the inflammation, imaging, inflammation + AFP, inflammation + imaging and nomogram were developed. Adding inflammation to imaging model can improve the AUC in training cohort (from 0.802 to 0.869), internal validation cohort (0.827 to 0.870), external validation cohort (0.740 to 0.802) and complete dataset cohort (0.739 to 0.788), and obtain more net benefit. The nomogram had excellent performance for predicting high-grade HCC in four cohorts (AUCs: 0.882 vs. 0.869 vs. 0.829 vs. 0.806) with a good calibration, and accessed at https://predict-solitaryhccgrade.shinyapps.io/DynNomapp/. Additionally, the nomogram obtained an AUC of 0.863 (95% CI 0.797–0.913) for predicting high-grade HCC in the HCC ≤ 3 cm. Kaplan–Meier survival curves demonstrated that the nomogram owned excellent stratification for HCC grade (P < 0.0001). This easy-to-use dynamic online nomogram hold promise for use as a noninvasive tool in prediction HCC grade with high accuracy and robustness. [ABSTRACT FROM AUTHOR]

Background: Cuproptosis is a recently identified form of programmed cell death and could be a new direction for tumour therapy, and it has important clinical implications. Long non-coding RNAs (lncRNAs) can intervene in diverse biological processes and have a decisive role in hepatocellular carcinoma (HCC). However, how cuproptosis-related lncRNAs (CRLs) participate in regulating HCC has yet to be recognised. This study aimed to establish and validate a prognostic signature of CRLs and to analyse their clinical value in HCC patients. Methods: To analyse the function of CRLs in the prognosis of HCC, RNA sequencing data, mutation data, and clinically relevant data were collected from the Cancer Genome Atlas Database (TCGA). Then, TCGA cohort was randomly divided into training and test sets. The training set was utilized to define prognostic signature of CRLs using bioinformatics methods. Subsequently, we verified the accuracy of this prognostic signature in the test set. Finally, we performed immune-related analysis, the half-maximal inhibitory concentration (IC50) prediction, gene set enrichment analysis, and tumour mutational burden (TMB) analysis. Results: We established a prognostic signature for the CRLs (SNHG4, AC026412.3, AL590705.3, and CDKN2A-DT). This signature-based risk group displayed an accurate predictive ability for the survival time of patients with HCC. We observed discrepancies in immune cells, immune function, the expression level of genes related to immune checkpoints, and TMB in high- and low-risk groups. Conclusion: This CRLs prognostic signature could predict clinical outcomes in patients with HCC as well as the efficacy of targeted and therapy immunotherapy. [ABSTRACT FROM AUTHOR]

Background: Hepatocellular carcinoma (HCC) is the most frequent primary liver tumor globally and a leading cause of mortality in cirrhotic patients. Our study aimed to estimate the diagnostic performance of triphasic CT and inter-observer reliability in the preoperative detection of microvascular invasion (MVI) in HCC. Two independent radiologists accomplished a retrospective analysis for 99 patients with HCC to assess the CT features for MVI in each lesion. Postoperative histopathology was considered the gold standard. Results: Multivariate regression analysis revealed that incomplete or absent tumor capsules, presence of TTPV, and absence of hypodense halo were statistically significant independent predictors of MVI. There was excellent agreement among observers in evaluating peritumoral enhancement, identifying intratumoral arteries, hypodense halo, TTPV, and macrovascular invasion. Also, our results revealed moderate agreement in assessing the tumor margin and tumor capsule. Conclusion: Triphasic CT features of MVI are reliable imaging predictors that may be helpful for standard preoperative interpretation of HCC. [ABSTRACT FROM AUTHOR]

We determined the value of computed tomography perfusion (CTP) for assessing the response of hepatocellular carcinoma (HCC) to transarterial chemoembolization (TACE). 20 post-TACE HCC patients were re-evaluated with contrast-enhanced computed tomography and CTP. Patients with persistent arterial vascularization [non-response (NR)] or those with no arterial vascularization in the mass, but with signs of new nodules, underwent digital subtraction angiography (DSA), which was used to analyze image characteristics and CTP parameters of TACE-treated HCC. 27 post-TACE HCC masses (mean size 4.21 cm, range 2-6.5 cm) were observed in the 20 patients. The values yielded by CTP were 78.30±40.41 mL/min/100g and 33.67±38.74 mL/min/100g for hepatic arterial blood flow (HABF) and 51.40±17.80% and 25.60±26.53% for hepatic arterial fraction (HAF) in the NR group and complete response group, respectively. The NR group's cutoff value of HABF was =55.95 mL/min/100g, with a sensitivity of 91.7% and specificity of 71.42%, and that of HAF was =32.55%, with a sensitivity of 92.3% and specificity of 83.33%. The CTP and DSA techniques showed high agreement in assessing the post-TACE responses of liver tumors (κ=0.872). The perfusion parameters HABF and HAF have high value for assessing post-TACE responses of HCC. [ABSTRACT FROM AUTHOR]

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Rewiring of cellular metabolism is now fully recognized as a hallmark of cancer. Tumor cells reprogram metabolic pathways to meet the energetic and macromolecular demands to support unrestricted growth and survival under unfavorable conditions. It is becoming apparent that these adaptations underpin most of the traits that define a cancer cell's identity, including the ability to avoid immune surveillance, endure nutrient and oxygen restrictions, detach and migrate from their natural histological niche, and avert human‐made aggressions (i.e., therapy). In a recent study, Benichou and collaborators identify carbohydrate‐responsive element‐binding protein (ChREBP), a master regulator of physiological glucose metabolism, as an oncogene in hepatocellular carcinoma (HCC) development. Upregulation of ChREBP expression results in a self‐stimulatory loop interconnecting PI3K/AKT signaling and glucose metabolism to feed fatty acid and nucleotide synthesis supporting tumorigenesis. Importantly, pharmacological inhibition of ChREBP activity quells in vivo HCC tumor growth without causing systemic toxicity. This study identifies novel oncometabolic pathways and open up new avenues to improve the treatment of a deadly tumor. [ABSTRACT FROM AUTHOR]

Objective: Describe the utility of circulating tumor DNA in the postoperative surveillance of hepatocellular carcinoma (HCC). Background: Current biomarkers for HCC like alpha-fetoprotein (AFP) are lacking. Circulating tumor DNA (ctDNA) has shown promise in colorectal and lung cancers, but its utility in HCC remains relatively unknown. Methods: Patients with HCC undergoing curative-intent resection from November 1, 2020, to July 1, 2023, received ctDNA testing using the Guardant360 platform. Tumor mutational burden (TMB) is calculated as the number of somatic mutations-per-megabase of genomic material identified. Results: Forty-seven patients had postoperative ctDNA testing. The mean follow-up was 27 months, and the maximum was 43.2 months. Twelve patients (26%) experienced recurrence. Most (n=41/47, 87.2%) had identifiable ctDNA postoperatively; 55.3% (n=26) were TMB-not detected versus 45.7% (n= 21) TMBdetectable. Postoperative identifiable ctDNA was not associated with RFS (P=0.518). Detectable TMB was associated with reduced RFS (6.9 vs 14.7 mo, P=0.049). There was a higher rate of recurrence in patients with TMB (n=9/21, 42.9%, vs n= 3/26, 11.5%, P=0.02). Area under the curve for TMB-prediction of recurrence was 0.752 versus 0.550 for AFP. ROC analysis established a TMB cutoff of 4.8mut/mB for predicting post-operative recurrence (P=0.002) and RFS (P=0.025). AFP was not correlated with RFS using the lab-normal cutoff (< 11 ng/mL, P=0.682) or the cutoff established by ROC analysis (=4.6 ng/mL, P=0.494). TMB-high was associated with poorer RFS on cox-regression analysis (hazard ratio=5.386, 95% CI: 1.109-26.160, P=0.037), while microvascular invasion (P= 0.853) and AFP (P=0.439) were not. Conclusions: Identifiable TMB on postoperative ctDNA predicts HCC recurrence and outperformed AFP in this cohort. Perioperative ctDNA may be a useful surveillance tool following curativeintent hepatectomy. Larger-scale studies are needed to confirm this utility and investigate additional applications in HCC patients, including the potential for prophylactic treatment in patients with residual TMB after resection. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) is a leading cause of cancer death. HCC is preventable with about 70% of HCC attributable to modifiable risk factors. Glucagon-like peptide-1 receptor agonists (GLP-1RAs), Food and Drug Administration–approved medications for treating type 2 diabetes mellitus (T2DM), have pleiotropic effects on counteracting risk factors for HCC. Here we evaluate the association of GLP-1RAs with incident HCC risk in a real-world population. This retrospective cohort included 1,890,020 patients with a diagnosis of T2DM who were prescribed GLP-1RAs or other non-GLP-1RA anti-diabetes medications and had no prior diagnosis of HCC. Incident (first-time) diagnosis of HCC and hepatic decompensating events during a 5-year follow-up was compared between cohorts of patients prescribed GLP-1 RAs vs other anti-diabetes medications. Time-to-first-event analysis was performed using Kaplan-Meier survival analysis with hazard ratio and 95% confidence interval calculated. GLP-1RAs were associated with a lower risk of incident HCC with hazard ratio of 0.20 [0.14–0.31], 0.39 [0.21–0.69], 0.63 [0.26–1.50] compared with insulin, sulfonylureas, and metformin, respectively. GLP-1RAs were associated with a significantly lower risk of hepatic decompensation compared with 6 other anti-diabetes medications. Reduced risks were observed in patients without and with different stages of fatty liver diseases, with more profound effects in patients without liver diseases. Similar findings were observed in patients with and without obesity and alcohol or tobacco use disorders. GLP-1RA combination therapies were associated with decreased risk for HCC and hepatic decompensations compared with monotherapies. GLP-1RAs were associated with a reduced risk of incident HCC and hepatic decompensation compared with other anti-diabetes medications in patients with T2DM. These findings provide supporting evidence for future studies to investigate the underlying mechanisms and their clinical use. Glucagon-like peptide-1 receptor agonists alone and in combination with other anti-diabetes medications were associated with a reduced risk of hepatocellular carcinoma incidence and hepatic decompensation events in patients with type 2 diabetes. [ABSTRACT FROM AUTHOR]

The efficacy of systemic therapy for unresectable advanced hepatocellular carcinoma (aHCC) has not been proven in patients with Child-Pugh (C-P) B cirrhosis. Nevertheless, in real-world these patients are treated both with tyrosine kinase inhibitors (TKIs) and with metronomic capecitabine (MC). This study aimed to compare sorafenib and MC outcomes versus best supportive care (BSC) in C-P B patients. Between 2008 and 2020, among 774 C-P B patients with aHCC not amenable/responsive to locoregional treatments, 410 underwent sorafenib, 62 MC, and 302 BSC. The propensity score matching method was used to correct the baseline unbalanced prognostic factors. In the unmatched population, median OS was 9.7 months in patients treated with sorafenib, 8.0 with MC, and 3.9 months with BSC. In sorafenib vs. BSC-matched patients (135 couples), median OS was 7.3 (4.9–9.6) vs. 3.9 (2.6–5.2) months (p <0.001). ECOG-Performance Status, tumor size, macrovascular invasion, AFP, treatment-naive, and sorafenib were independent predictors of survival. In MC vs. BSC-matched patients (40 couples), median OS was 9.0 (0.2–17.8) vs.3.0 (2.2–3.8) months (p <0.001). Median OS did not differ (p = 0.283) in sorafenib vs. MC-matched patients (55 couples). C-P B patients with aHCC undergoing BSC have poor survival. Both Sorafenib and MC treatment improve their prognosis. [ABSTRACT FROM AUTHOR]

Portal hypertension (PHT) often complicates hepatocellular carcinoma (HCC) treatment and prognosis. We aimed to assess PHT's impact on AtezoBev outcomes and identify predictors of acute variceal bleeding (AVB) and clinical ascites occurrence. A prospective cohort of 200 HCC patients treated with AtezoBev was studied alongside a retrospective cohort of 123 patients treated with Sorafenib. We assessed factors influencing progression-free survival (PFS), overall survival (OS), AVB and clinical ascites development, focusing on PHT parameters, and comparing outcomes within and between the two cohorts (time-dependent Cox model and adjusted survival curves). Among the AtezoBev cohort, 10% experienced AVB, 24% had high-risk esophageal varices (EV) and 46% vascular invasion. Median PFS and OS in the AtezoBev cohort was 5.13 and 12.2 months. AVB (HR=1.81;[95%CI:1.03–3.17]) and clinical ascites occurrence (HR=2.29;[95%CI:1.52–3.45]) were independently associated with mortality. AVB incidence was 12% at 12 months in AtezoBev patients and EV, history of AVB<6months and vascular invasion were independently associated with AVB. The Sorafenib cohort had shorter median PFS and OS, with similar AVB incidence and only EV were associated with AVB. PHT-related events significantly affect not only liver decompensation but also OS in AtezoBev-treated patients. We suggest a more widespread use of NSBB to prevent liver decompensation, with intensified prophylaxis for high-risk patients. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related deaths worldwide. Extensive research is currently directed at identifying novel targets for its diagnosis and treatment. We investigated the biological functions and clinical significance of mucin-type N-acetylglucosaminyltransferase 3 (GCNT3) in HCC. Variations in the mRNA expression of GCNT3 were examined in normal and HCC tissues. Cell function assays and animal models characterized the effects of GCNT3 on the proliferation, invasion, and migration abilities of HCC cells. Western blot and immunofluorescence analyses were performed to explore further the specific mechanisms whereby GCNT3 affects HCC progression. There is a strong correlation between GCNT3 overexpression and tumor formation and metastasis in vivo and in vitro. GCNT3 acted as a regulator of the synthesis of mucin-type O-glycans by interacting with mucin 13 (MUC13) to regulate its expression levels, activating the GSK3β/β-catenin signaling pathway. The activation of GSK3β/β-catenin signaling by GCNT3 was mitigated by MUC13 knockdown. In clinical HCC specimens, GCNT3 expression was upregulated in HCC tissues compared to non-tumor tissues. Further, there was a significant correlation between high GCNT3 expression and poor patient survival. GCNT3 regulated tumor progression in HCC through the MUC13/GSK3-β/β-catenin signaling pathway. [ABSTRACT FROM AUTHOR]

Background: This study aims to identify trends, research gaps, leading journals, institutions, countries, and authors by examining the top 100 cited Yttrium-90 Radioembolization (Y90) research articles. The insights gained will assist funding and collaboration efforts in Y90 research. The team analyzed 981 articles from 36 peer-reviewed journals, gathering data on authors, publication year, journal, citations, affiliations, keywords, and references. Author affiliations were scrutinized to pinpoint institutions and countries. p values < 0.05 were deemed statistically significant. The most cited paper (703 citations) was authored by Salem et al. (2010), and the journal with the most publications (16) was Journal of Vascular and Interventional Radiology. There was no significant correlation between journal impact factor and citation metrics. A decreasing trend in the number of top 100 articles was observed since the peak period (2008–2013). Most papers were published in high-impact factor (IF > 3, n = 31/35) and SCImago Q1 journals (86/100), with Northwestern University, Clínica Universidad de Navarra, and Ludwig Maximilian University of Munich being the leading institutions. The most prolific authors were Salem, R., Lewandowski, R.J., and Mulcahy, M.F., with Salem, R. as the most influential. A statistically significant positive correlation between collaborative links and published articles was also discovered. Short conclusion: The top 100 cited articles were primarily published in high-impact journals, and Northwestern University and the USA showed greater productivity and collaboration. These findings have crucial implications for researchers, policymakers, and institutions, aiding in the improvement of Y90 application and understanding in clinical practice. [ABSTRACT FROM AUTHOR]

Introduction: This study examined associations between the graft-to-recipient weight ratio (GRWR) for adult-to-adult living donor liver transplantation (LDLT) and hepatocellular carcinoma (HCC) outcomes. Materials and Methods: Data from patients in the Korean Organ Transplantation Registry who underwent LDLT for HCC from 2014 to 2021 were retrospectively reviewed. Patients were categorized using the cutoff GRWR for HCC recurrence determined by an adjusted cubic spline (GRWR <0.7% vs. GRWR =0.7%). Recurrence-free survival (RFS) and HCC recurrence were analyzed in the entire and a 1:5 propensity-matched cohort. Results: The eligible cohort consisted of 2005 LDLT recipients [GRWR <0.7 (n =59) vs. GRWR =0.7 (n= 1946)]. In the entire cohort, 5-year RFS was significantly lower in the GRWR <0.7 than in the GRWR =0.7 group (66.7% vs. 76.7%, P=0.019), although HCC recurrence was not different between groups (77.1% vs. 80.7%, P= 0.234). This trend was similar in the matched cohort (P =0.014 for RFS and P= 0.096 for HCC recurrence). In multivariable analyses, GRWR <0.7 was an independent risk factor for RFS [adjusted hazard ratio (aHR) 1.89, P =0.012], but the result was marginal for HCC recurrence (aHR 1.61, P= 0.066). In the pretransplant tumor burden subgroup analysis, GRWR <0.7 was a significant risk factor for both RFS and HCC recurrence only for tumors exceeding the Milan criteria (aHR 3.10, P< 0.001 for RFS; aHR 2.92, P=0.003 for HCC recurrence) or with MoRAL scores in the fourth quartile (aHR 3.33, P<0.001 for RFS; aHR 2.61, P= 0.019 for HCC recurrence). Conclusions: A GRWR <0.7 potentially leads to lower RFS and higher HCC recurrence after LDLT when the pretransplant tumor burden is high. [ABSTRACT FROM AUTHOR]

Given the limited sensitivity of ultrasound in hepatocellular carcinoma (HCC) surveillance, this systematic review and meta-analysis were aimed to assess the diagnostic performance of non-contrast abbreviated MRI (NC-aMRI) compared to contrast-enhanced abbreviated MRI (CE-aMRI) for HCC surveillance, offering evidence-based guidance for clinical decision-making. A comprehensive search was conducted across five databases, identifying studies on aMRI for HCC surveillance. The pooled sensitivity and specificity were estimated using a random effects model. Subgroup analyses and meta-regression were performed by study location, proportion of patients with cirrhosis and HCC, and underlying liver diseases. The meta-analysis included 27 studies (2009–2023), distributed between Western (n = 14) and Eastern (n = 13) countries. The pooled sensitivity and specificity (95%CI, I 2 ) were 86% (83–88%, 63%) and 92% (90%–94%, 74%). The NC-aMRI protocols reported in 21 studies exhibited 83% (79–87%, 63%) sensitivity and 91% (88–93%, 67%) specificity, while the 15 studies on CE-aMRI protocols displayed 88% (84–91%, 64%) sensitivity and 94% (90–96%, 78%) specificity, with no statistically significant differences in sensitivity (p = 0.078) or specificity (p = 0.157). Subgroup analysis in NC-aMRI studies showed significant differences in sensitivity for high-prevalent chronic hepatitis B (87% vs. 78%, p = 0.003) and studies done in eastern countries (86% vs. 76%, p = 0.018). Additionally, specificity showed significant differences for high-prevalent chronic hepatitis C (94% vs. 90%, p = 0.009), with meta-regression identifying major sources of study heterogeneity as the inclusion of a majority of patients with chronic hepatitis B (p = 0.008) and the geographic regions where studies were conducted (p = 0.030). Surveillance aMRI protocols exhibit satisfactory performance for detecting HCC. NC-aMRI may be used effectively for HCC surveillance, especially in chronic hepatitis B prevalent settings. [ABSTRACT FROM AUTHOR]

High expression of phosphatidylinositol 4-kinase III alpha (PI4KIIIα) correlates with poor survival rates in patients with hepatocellular carcinoma. In addition, hepatitis C virus (HCV) infections activate PI4KIIIα and contribute to hepatocellular carcinoma progression. We aimed at mechanistically understanding the impact of PI4KIIIα on the progression of liver cancer and the potential contribution of HCV in this process. Several hepatic cell culture and mouse models were used to study the functional importance of PI4KIIIα on liver pathogenesis. Antibody arrays, gene silencing, and PI4KIIIα-specific inhibitor were applied to identify the involved signaling pathways. The contribution of HCV was examined by using HCV infection or overexpression of its nonstructural protein. High PI4KIIIα expression and/or activity induced cytoskeletal rearrangements via increased phosphorylation of paxillin and cofilin. This led to morphologic alterations and higher migratory and invasive properties of liver cancer cells. We further identified the liver-specific lipid kinase phosphatidylinositol 3-kinase C2 domain-containing subunit gamma (PIK3C2γ) working downstream of PI4KIIIα in regulation of the cytoskeleton. PIK3C2γ generates plasma membrane phosphatidylinositol 3,4-bisphosphate–enriched, invadopodia-like structures that regulate cytoskeletal reorganization by promoting Akt2 phosphorylation. PI4KIIIα regulates cytoskeleton organization via PIK3C2γ/Akt2/paxillin-cofilin to favor migration and invasion of liver cancer cells. These findings provide mechanistic insight into the contribution of PI4KIIIα and HCV to the progression of liver cancer and identify promising targets for therapeutic intervention. [Display omitted] Two lipid kinases orchestrate a novel signaling pathway connecting phospholipids to progression of liver cancer, unraveling promising targets for therapeutic intervention. [ABSTRACT FROM AUTHOR]

Laparoscopic hepatectomy (LH) has become a common surgery for the treatment of liver tumor. To evaluate the surgical quality of laparoscopic hepatectomy under the context of precision surgery with Textbook outcome (TO), a comprehensive and holistic assessment approach. A total of 1056 patients who underwent laparoscopic hepatectomy from May 2016 and December 2022 were enrolled in the study. All the patients were performed hepatectomy. The rate of TO and factors associated with achieving TO were examined. Among the 1056 patients, 75 % patients achieved TO. The main reason limited patients achieving textbook outcomes was prolonged length of hospital stay (LOS). The univariate analysis indicated that age>65, ASA classification ≥3, liver cirrhosis, tumor size > 3 cm, tumor number ≥2, type of primary cancer, and IWATE DSS were significantly associated with non-achievement of TO. The multivariate analysis indicated that the ASA classification ≥3 and advanced difficulty level in IWATE DSS independent factors associated with achieving TO. Reaching TO can significantly prolong the postoperative recurrence time and overall survival time of hepatocellular carcinoma patients. In the context of precision surgery, 75 % patients undergoing laparoscopic hepatectomy achieved a TO. Patients who achieved TO had significantly improved survival. [ABSTRACT FROM AUTHOR]

Metabolic dysfunction‐associated steatohepatitis‐driven hepatocellular carcinoma (MASH‐HCC) is a global clinical challenge for which there is a limited understanding of disease pathogenesis and a subsequent lack of therapeutic interventions. We previously identified that tumor necrosis factor‐alpha (TNF‐α) upregulated apoptosis antagonizing transcription factor (AATF) in MASH. Here, we investigated the effect of TNF‐α converting enzyme (TACE) inhibition as a promising targeted therapy against AATF‐mediated steatohepatitis to hepatocarcinogenesis. A preclinical murine model that recapitulates human MASH‐HCC was used in the study. C57Bl/6 mice were fed with chow diet normal water (CD) or western diet sugar water (WD) along with a low dose of carbon tetrachloride (CCl4; 0.2 μL·g−1, weekly) for 24 weeks. TACE activity, TNF‐α levels, and AATF expression were measured. The mice were treated with the TACE inhibitor Marimastat for 12 weeks, followed by analyses of liver injury, fibrosis, inflammation, and oncogenic signaling. In vitro experiments using stable clones of AATF control and AATF knockdown were also conducted. We found that AATF expression was upregulated in WD/CCl4 mice, which developed severe MASH at 12 weeks and advanced fibrosis with HCC at 24 weeks. WD/CCl4 mice showed increased TACE activity with reduced hepatic expression of sirtuin 1 (Sirt1) and tissue inhibitor of metalloproteinase 3 (Timp3). The involvement of the SIRT1/TIMP3/TACE axis was confirmed by the release of TNF‐α, which upregulated AATF, a key molecular driver of MASH‐HCC. Interestingly, TACE inhibition by Marimastat reduced liver injury, dyslipidemia, AATF expression, and oncogenic signaling, effectively preventing hepatocarcinogenesis. Furthermore, Marimastat inhibited the activation of JNK, ERK1/2, and AKT, which are key regulators of tumorigenesis in WD/CCl4 mice and in AATF control cells, but had no effect on AATF knockdown cells. This study shows that TACE inhibition prevents AATF‐mediated inflammation, fibrosis, and oncogenesis in MASH‐HCC, offering a potential target for therapeutic intervention. [ABSTRACT FROM AUTHOR]

Background: Lenvatinib plus programmed death-1 (PD-1) inhibitors (LEN-P) have been recommended in China for patients with advanced hepatocellular carcinoma (HCC). However, they provide limited survival benefits to patients with extrahepatic metastases. We aimed to investigate whether combining hepatic arterial infusion chemotherapy (HAIC) with LEN-P could improve its efficacy. Materials and methods: This multicenter cohort study included patients with HCC extrahepatic metastases who received HAIC combined with LEN-P (HAIC-LEN-P group, n=127) or LEN-P alone (n= 103) as the primary systemic treatment between January 2019 and December 2022. Baseline data were balanced using a one-to-one propensity score matching (PSM) and inverse probability of treatment weighting (IPTW). Results: After PSM, the HAIC-LEN-P group significantly extended the median overall survival (mOS) and median progression-free survival (mPFS), compared with the LEN-P group (mOS: 27.0 months vs. 9.0 months, P<0.001; mPFS: 8.0 months vs. 3.0 months, P=0.001). After IPTW, themOS [hazard ratio (HR)=0.384, P<0.001] andmPFS (HR=0.507, P<0.001) were significantly higher in the HAIC-LEN-P group than in the LEN-P group. The HAIC-LEN-P group's objective response rate was twice as high as that of the LEN-P group (PSM cohort: 67.3% vs. 29.1%, P<0.001; IPTW cohort: 66.1% vs. 27.8%, P<0.001). Moreover, the HAIC-LEN-P group exhibited no noticeable increase in the percentages of grade 3 and 4 adverse events compared with the LEN-P group (P>0.05). Conclusion: HAIC can improve the efficacy of LEN-P in patients with HCC extrahepatic metastases and may be an alternative treatment for advanced HCC management. [ABSTRACT FROM AUTHOR]

Les carcinomes hépatocellulaires (CHC) sont les tumeurs hépatiques primitives du foie les plus fréquentes. Ils représentent la seconde cause de mortalité liée au cancer dans le monde. Les principaux facteurs étiologiques incluent les hépatites virales B et C, la prise chronique d'alcool et les syndromes métaboliques. Nous focaliserons cette revue sur l'impact de l'infection par le virus de l'hépatite B (VHB) et la progression de l'atteinte hépatique vers le CHC. Des mécanismes à la fois directs et indirects à l'infection par le VHB contribuent à l'émergence d'un CHC. Nous aborderons ces deux types de mécanismes en nous concentrant sur les effets viraux directs, explorés dans de très nombreuses études in vivo et in vitro. Les résultats publiés peuvent parfois être contradictoires. Ils varient notamment en fonction du modèle d'étude, de la séquence virale, du niveau d'expression du VHB, du type de génome viral transféré (partiel ou complet), de la méthode de transfert, générant une expression stable ou transitoire, et de bien d'autres paramètres. Néanmoins, les connaissances acquises récemment sur le cycle viral, et en particulier sur la nature du récepteur hépatocytaire du VHB, permettent aujourd'hui de reproduire in vitro un cycle viral complet dans différents modèles expérimentaux et ainsi de mieux apprécier les activités pro-tumorales de l'infection par le VHB. Cette revue est bien évidemment non exhaustive et les connaissances, notamment sur la prise en charge clinique et thérapeutique du CHC qu'il soit associé à la présence du VHB ou non, sont actuellement en pleine évolution avec l'essor des immunothérapies combinées. Hepatocellular carcinomas (HCC) are the most common primary liver tumours. They are the second leading cause of cancer-related mortality worldwide. The main etiological factors include viral hepatitis B and C, chronic alcohol intake and metabolic syndromes. We will focus this review on the impact of hepatitis B virus (HBV) infection and the progression of liver damage to HCC. Both direct and indirect mechanisms of HBV infection contribute to the emergence of HCC. We will address these two types of mechanisms by focusing on direct viral effects, explored in numerous in vivo and in vitro studies. Published results can sometimes be contradictory. They vary depending on the study model, the viral sequence, the level of HBV expression, the type of viral genome transferred (partial or complete), the transfer method, generating a stable or transient expression, and many other parameters. Nevertheless, the knowledge acquired recently on the viral cycle, and in particular on the nature of the hepatocyte receptor of HBV, allows today to reproduce in vitro a complete viral cycle in different experimental models and thus, to better appreciate the pro-tumor activities of HBV infection. This review is obviously not exhaustive and the knowledge, particularly on the clinical and therapeutic management of HCC, whether associated with the presence of HBV or not, is currently evolving with the rise of combined immunotherapies. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate the efficacy and safety of transarterial chemoembolization (TACE) combined with Lenvatinib plus sequential microwave ablation (MWA) for the treatment of patients with large hepatocellular carcinoma (HCC) beyond up-to-seven criteria. This retrospective cohort study assessed the medical records of patients with large HCC who underwent TACE combined with Lenvatinib plus sequential MWA (TLM) or TACE plus sequential MWA (TM). Lenvatinib was administered to patients within 3–5 days after TACE and sequential MWA was performed once they met the criteria for curative ablation after TACE or the combination therapy. The progression-free survival (PFS), overall survival (OS) and treatment-related complications were compared between two groups. Of the 81 patients who underwent TLM or TM, 64 who met the eligibility criteria were included in this study. Among them, 28 patients underwent TLM and 36 underwent TM. The inverse probability weighting method (IPTW) was used to balance differences between two groups. The TLM group had longer PFS than the TM group (median, before IPTW: 18.53 vs. 5.62 months, p < 0.001; median, after IPTW: 28.27 vs. 5.30 months, p < 0.001). Univariate and multivariate analyses revealed that TLM and the maximum tumor diameter were independent prognostic factors for PFS. The overall incidence rate of minor complications related to TACE or MWA was lower in the TLM group (32.1% vs. 66.7%, p = 0.006). TACE combined with Lenvatinib plus sequential MWA can prolong the progression-free survival of patients with large HCC beyond up-to-seven criteria. [ABSTRACT FROM AUTHOR]

Radiofrequency ablation (RFA) is a potentially curative treatment option for early Hepatocellular carcinoma. The RFA is considered safe with a relatively low incidence of complications ranging from 2%−7.9%. Though most of the complications are self-limiting, sometimes they can be life-threatening. The occurrence of the particular complication depends on various factors like tumour location and morphology, underlying disease and ablation technique. A detailed understanding of potential complications along with the associated risk factors will help to employ strategies to prevent them, identify them early and manage them when they occur. This article demonstrates various radiofrequency ablation-related complications and discusses the risk factors and technical strategies to minimise them and achieve complete ablation of the tumour. [ABSTRACT FROM AUTHOR]

Combination immunotherapy has shown promising potential for enhancing the objective response rate compared to immune checkpoint blockade (ICB) monotherapy. However, combination therapy with multi-drugs is limited by the different properties of the agents and inconsistent synergistic targeted delivery. Herein, based on a universal triterpene template and the anticancer active agent ursolic acid (UA), a cytomembrane-coated biomimetic delivery nanoplatform (UR@M) prepared by the self-assembly of a PD-L1 targeted CRISPR/Cas9 system and UA was designed for hepatocellular carcinoma (HCC) treatment. UR@M showed enhanced tumor accumulation in vivo with homologous tumor targeting, and CRISPR in the nanosystem exhibited potent gene-editing efficiency of 76.53% in vitro and 62.42% in vivo with no off-target effects. UA activated the natural immune system through the TLR-2-MyD88-TRAF6 pathway, which synergistically enhanced the proliferation of natural killer cells and dendritic cells and realized excellent immune cytotoxic T cell infiltration by combining with the ICB of PD-L1. The strategy of work along both lines based on innate immune and adaptive immunity displayed a significant effect in tumor regression. Overall, the UA-templated strategy "killed three birds with one stone" by establishing a self-assembly nanosystem, inducing tumor cell death, and promoting synergistic immunostimulation for HCC treatment. A biomimetic nanodrug UR@M from the triterpenoids-templated self-assembly is developed to deliver CRISPR/Cas9, exhibiting synergistic immunotherapy by activating innate immune by TLR-2 pathway and gene therapy of PD-L1 by CRISPR/Cas9. [Display omitted] [ABSTRACT FROM AUTHOR]

Objectives: This study aimed to investigate the efficacy and safety of programmed cell death-1 (PD-1)/programmed death ligand 1 (PD-L1) inhibitors in patients with advanced hepatocellular carcinoma (HCC). Materials and Methods: PubMed, EMBASE, and the Cochrane Library were searched for articles published until November 2022. Studies reporting the efficacy of PD-1/PD-L1 inhibitors in patients with advanced HCC were eligible for inclusion. The outcomes were objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and = Grade 3 treatment-related adverse events (TrAEs). Results: Fourteen trials with 4515 patients with HCC were included. Our results showed that treatment with PD-1/PD-L1 inhibitors was associated with better ORR and DCR than that with control (placebo or sorafenib or lenvatinib) (odds ratio [OR], 3.89; 95% confidence interval (CI), 2.55-5.95 and OR, 1.47; 95% CI, 1.11-1.95, respectively). The overall hazard ratio (HR) of PFS and OS were 0.66 (95% CI 0.56-0.78) and 0.65 (95% CI 0.55-0.77), respectively. In subgroup analysis, PD-1/PD-L1 inhibitor combination therapy had an advantage in terms of PFS (HR: 0.57 vs. 0.81) compared to that of PD-1/PD-L1 monotherapy. The incidence of grade 3-5 TrAEs was not significantly higher with PD-1/PD-L1 inhibitors than that with the control (OR, 1.12; 95% CI, 0.70-1.81). However, the combination of PD-1inhibitor with higher incidence of Grade 3-5 TrAEs (OR: 2.04, 95% CI 0.66-6.32) than the combination PD-L1 inhibitor (OR: 0.95, 95% CI 0.50-1.81). Conclusion: The combination of PD-1/PD-L1 inhibitors and targeted agents significantly improved the clinical outcomes in patients with advanced HCC. However, the incidence of Grade 3-5 TrAEs with PD-1 inhibitor combination therapy was higher than the combination PD-L1 inhibitor. [ABSTRACT FROM AUTHOR]

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Objective: Examine portal hypertension (PHT) impact on postoperative and survival outcomes in hepatocellular carcinoma (HCC) patients after liver resection (LR), specifically exploring distinctions between indirect signs and invasive measurements of PHT. Background: PHT has historically discouraged LR in individuals with HCC due to the elevated risk of morbidity, including liver decompensation (LD). Methods: A systematic review was conducted using 3 databases to identify prospective-controlled and matched cohort studies until December 28, 2022. Focus on comparing postoperative outcomes (mortality, morbidity, and liver-related complications) and overall survival in HCC patients with and without PHT undergoing LR. Three meta-analysis models were utilized: for aggregated data (fixed-effects inverse variance model), for patient-level survival data (one-stage frequentist meta-analysis with gamma-shared frailty Cox proportional hazards model), and for pooled data (Freeman--Tukey exact and double arcsine method). Results: Nine studies involving 1124 patients were analyzed. Indirect signs of PHT were not significantly associated with higher mortality, overall complications, PHLF or LD. However, LR in patients with hepatic venous pressure gradient (HVPG) ≥ 10 mm Hg significantly increased the risk of overall complications, PHLF, and LD. Despite elevated risks, the procedure resulted in a 5-year overall survival rate of 55.2%. Open LR significantly increased the risk of overall complications, PHLF, and LD. Conversely, PHT did not show a significant association with worse postoperative outcomes in minimally invasive LR. Conclusions: LR in the presence of indirect signs of PHT poses no increased risk of complications. Yet, in HVPG ≥ 10 mm Hg patients, LR increases overall morbidity and liver-related complications risk. Transjugular HVPG assessment is crucial for LR decisions.Minimally invasive approach seems to be vital for favorable outcomes, especially in HVPG ≥ 10 mm Hg patients. [ABSTRACT FROM AUTHOR]

Sarcopenia accompanied by systemic inflammation is associated with poor prognosis in patients with advanced hepatocellular carcinoma (HCC). However, the effect of sarcopenia combined with systemic inflammation on the prognosis of patients with advanced HCC who underwent hepatectomy is unclear. This study aimed to evaluate the effect of sarcopenia and inflammation on the prognosis of patients with advanced HCC. This retrospective study included 151 patients recruited between July 2010 and December 2022. We defined advanced HCC as that presenting with vascular invasion or tumor size ≥2 cm or multiple tumors. Sarcopenia was assessed using the psoas muscle index. Preoperative inflammatory markers were used by calculating the prognostic nutritional index, albumin-globulin ratio (AGR), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio. Cox regression analysis was performed to determine the prognostic factors for overall survival. Of 151 patients, sarcopenia occurred in 84 (55.6 %). Sarcopenia was significantly associated with male sex, older age, body mass index (<25 kg/m2), and a higher NLR. In the multivariate analysis, AGR <1.25 (hazard ratio [HR], 2.504; 95% confidence interval [CI]: 1.325–4.820; p < 0.05); alpha-fetoprotein levels ≥25 ng/mL (HR, 1.891; 95% CI: 1.016–3.480; p = 0.04); and sarcopenia (HR, 1.908; 95% CI: 1.009–3.776; p < 0.05) were independent predictors of overall survival. The sarcopenia and low AGR groups had significantly worse overall survival than either the non-sarcopenia and high AGR or sarcopenia and low AGR groups. Sarcopenia and AGR are independent prognostic factors in patients with advanced HCC. Thus, sarcopenia may achieve a better prognostic value when combined with AGR. [ABSTRACT FROM AUTHOR]

This study aimed to compare the effectiveness of liver resection (LR) and microwave ablation (MWA) in hepatocellular carcinoma (HCC) patients with early recurrence and varying stages of cirrhosis. This study analyzed patients with HCC who underwent hepatectomy and experienced early tumor recurrence (≤3 cm) between December 2002 and December 2020 at the Tongji Hospital. Treatment effectiveness was assessed using a propensity score matching (PSM) analysis. This study included 295 patients (106, LR; 189, MWA), 86 patients in each of the 2 groups were chosen for further comparison, after PSM. After PSM, both LR and MWA demonstrated similar recurrence-free survival (RFS) and overall survival (OS) rates (p = 0.060 and p = 0.118, respectively). However, the LR group had more treatment-related complications. In patients with moderate or severe cirrhosis, no significant differences in RFS or OS rates were found between the LR and MWA groups (p = 0.779 and p = 0.772, respectively). In patients without cirrhosis or with mild cirrhosis, LR showed better RFS and OS rates than MWA (p = 0.024 and p = 0.047, respectively). Multivariate analysis after PSM identified moderate or severe cirrhosis and recurrence intervals ≤12 months as independent predictors of poor RFS and OS in patients with early recurrence of HCC. LR is more effective than MWA for early recurrence of HCC in patients without cirrhosis or with mild cirrhosis, showing improved RFS and OS rates. In patients with moderate or severe cirrhosis, the OS and RFS were statistically equal between the two therapies. However, MWA may be preferred owing to its low complication rate. [ABSTRACT FROM AUTHOR]

Locoregional therapy and multi-kinase inhibitor agent have been the backbone of treatment for hepatocellular carcinoma (HCC) patients. However, the effect of combination or sequential use of locoregional therapy on HCC patients receiving multi-kinase inhibitor remain uncertain. Therefore, we aim to explore whether the subsequent locoregional therapy provides better survival in HCC patients under lenvatinib treatment. From March 2018 to April 2020, a total of 78 unresectable HCC patients receiving lenvatinib were recruited. Image response was evaluated by dynamic image using the modified RECIST criteria. Among patients with tumor progression under lenvatinib treatment, whether receiving subsequent locoregional therapy or not were documented. Overall survival between two groups and the predictors for tumor progression were also analyzed. Among the 78 patients receiving lenvatinib, the median age was 67.8 years old, and 69.2 % were male. Forty-four patients (56.4 %) experienced tumor progression with time to progression 5.1 months (95 % confidence interval (CI): 4.7–6.8) months. In multivariable Cox regression analysis, albumin-bilirubin (ALBI) grade II (adjusted HR: 2.883, P = 0.0104), and treatment duration less than three months (adjusted HR: 3.801, P = 0.0014) were the independent predictive factors for tumor progression, while patients achieving objective response under lenvatinib treatment within 12 weeks was the independent protective factor for tumor progression (adjusted HR: 0.144, P = 0.0020). Among the 44 patients with tumor progression, twenty-six (59.1 %) patients received subsequent locoregional therapy after tumor progression. Comparing to those with tumor progression without locoregional treatment, patients who received subsequent locoregional therapy had significantly better survival (1st year cumulative survival rate 70 % vs 27 %, log-rank P = 0.003). ALBI grade, treatment duration of lenvatinib, and achieving objective image response within twelve weeks were the independent predictive factors for tumor progression. Furthermore, longer overall survival was observed in tumor progression patients with subsequent locoregional therapy and with better liver preserved function. [ABSTRACT FROM AUTHOR]

Background: The high incidence of early recurrence after liver resection (LR) for hepatocellular carcinoma (HCC) is the main obstacle in achieving good long-term survival outcomes. The aim of the present study is to develop a prognostic model in predicting the risk of very early (1-year) recurrence. Material and methods: Consecutive patients who underwent LR for HCC with curative intent at multicenters in China were enrolled in this study. The VERM-pre (the Preoperative Very Early Recurrence Model of HCC) with good performance was derived and validated by internal and external cohorts retrospectively and by another two-center cohort prospectively. Results: Seven thousand four hundred one patients were enrolled and divided randomly into three cohorts. Eight variables (tumor diameter, tumor number, macrovascular invasion, satellite nodule, alpha-fetoprotein, level of HBV-DNA, γ-GT, and prothrombin time) were identified as independent risk factors for recurrence-free survival on univariate and multivariate analyses. The VERM-pre model was developed which showed a high capacity of discrimination (C-index: 0.722; AUROC at 1-year: 0.722)) and was validated comprehensively by the internal, external, and prospective cohorts, retrospectively. Calibration plots showed satisfactory fitting of probability of early HCC recurrence in the cohorts. Three risk strata were derived to have significantly different recurrence-free survival rates (low-risk: 80.4-85.4%; intermediate-risk: 59.7-64.8%; high-risk: 32.6-42.6%). In the prospective validation cohort, the swimming plot illustrated consistent outcomes with the beginning predictive score. Conclusion: The VERM-pre model accurately predicted the 1-year recurrence rates of HCC after LR with curative intent. The model was retrospectively and prospectively validated and then developed as the online tool. [ABSTRACT FROM AUTHOR]

To explore and compare the performance of LI-RADS® and radiomics from multiparametric MRI in predicting microvascular invasion (MVI) preoperatively in patients with solitary hepatocellular carcinoma (HCC) < 5 cm. We enrolled 143 patients with pathologically proven HCC and randomly stratified them into training (n = 100) and internal validation (n = 43) cohorts. Besides, 53 patients were enrolled to constitute an independent test cohort. Clinical factors and imaging features, including LI-RADS and three other features (non-smooth margin, incomplete capsule, and two-trait predictor of venous invasion), were reviewed and analyzed. Radiomic features from four MRI sequences were extracted. The independent clinic-imaging (clinical) and radiomics model for MVI-prediction were constructed by logistic regression and AdaBoost respectively. And the clinic-radiomics combined model was further constructed by logistic regression. We assessed the model discrimination, calibration, and clinical usefulness by using the area under the receiver operating characteristic curve (AUC), calibration curve, and decision-curve analysis respectively. Incomplete tumor capsule, corona enhancement, and radiomic features were related to MVI in solitary HCC ＜ 5 cm. The clinical model achieved AUC of 0.694/0.661 (training/internal validation). The single-sequence-based radiomic model's AUCs were 0.753–0.843/0.698–0.767 (training/internal validation). The combination model exhibited superior diagnostic performance to the clinical model (AUC: 0.895/0.848 [training/ internal validation]) and yielded an AUC of 0.858 in an independent test cohort. Incomplete tumor capsule and corona enhancement on preoperative MRI were significantly related to MVI in solitary HCC ＜5 cm. Multiple-sequence radiomic features potentially improve MVI-prediction-model performance, which could potentially help determining HCC's appropriate therapy. [ABSTRACT FROM AUTHOR]

Anxiety is a common problem in patients scheduled for a procedure, and their level of anxiety increases as the procedure date approaches; pre-procedural anxiety is observed in hepatocellular carcinoma (HCC) patients scheduled for liver ablation treatment. There is currently a lack of standardized education provided to patients about liver ablation treatment, which may contribute to patients' anxiety. To test the effectiveness of a pre-procedural video educational tool to reduce patient anxiety and increase knowledge in HCC patients in an interventional radiology clinic setting. This was a quasi-experimental, single-arm study, with a pre-test/post-test. Participant recruitment was based on a convenience sample. Inclusion criteria included: patients ages 18 and older; have biopsy-proven HCC or have a liver mass suspicious for HCC based on LI-RADS criteria imaging; no prior liver ablation treatment within three months of study onset. Participants watched a 7:04 minutes video and completed a 40-item State-Trait Anxiety Inventory and 10-item Knowledge Questionnaire before and after the video intervention to assess changes in anxiety and knowledge. Demographic variables evaluated included age, gender, education, and primary language. There were 16 participants who met inclusion criteria. The state anxiety scores were significantly lower after the intervention (Md = 33.50, n = 16) compared to before (Md = 47.50, n = 16), z = −2.67, p =.009, with a medium effect size, r = 0.47. The trait anxiety scores did not show sufficient evidence for a difference after the intervention (Md = 40.00, n = 16) compared to before (Md = 39.50, n = 16), z = 0.71, p =.50, with a small effect size, r = 0.13. The knowledge scores were significantly higher after the intervention (Md = 9.00, n = 16) compared to before (Md = 2.00, n = 16), z = −3.53, p =.0005, with a large effect size, r = 0.62. A nonparametric bootstrap and nonparametric permutation test also showed evidence for a difference in mean between the distributions of the state anxiety and knowledge pre- and post-intervention scores. The results of this study showed evidence for the effectiveness of video education in decreasing anxiety and increasing knowledge in HCC patients. A standardized pre-procedural video educational tool can be a useful practice across all interventional radiology departments as it is associated with improved quality of care and positive health outcomes. • Surgical procedures can cause anxiety in cancer patients. • Preprocedural video education in liver cancer patients decreases anxiety. • Early video education increases patient knowledge. [ABSTRACT FROM AUTHOR]

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a leading cause of chronic liver disease with increasing numbers worldwide. Adipokines like apelin (APLN) can act as key players in the complex pathophysiology of MASLD. Investigating the role of APLN in MASLD. Fecal and blood samples were collected in a MASLD cohort and healthy controls (HC). MASLD patients with liver fibrosis and MASLD-associated hepatocellular carcinoma (HCC) were included into the study. Systemic concentration of Apelin, Apelin receptor (APLNR) and circulating cytokines were measured in serum samples. Apelin concentration correlated with the Fib-4 score and was elevated in MASLD patients (mild fibrosis, mF (Fib-4 <3.25) and severe fibrosis, sF (Fib-4 >3.25)) as well as in MASLD-associated HCC patients compared to HC. In accordance APLNR and circulating cytokines were also elevated in mF and sF. In contrast apelin levels were negatively associated with liver survival at three and five years. Changes in taxa composition at phylum level showed an increase of Enterobactericae, Prevotellaceae and Lactobacillaceae in patients with sF compared to mF. We could also observe an association between apelin concentrations and bacterial lineages (phyla). Circulating apelin is associated with liver fibrosis and HCC. In addition, there might exist an interaction between systemic apelin and the gut microbiome. [ABSTRACT FROM AUTHOR]

Due to soared obesity population worldwide, hepatosteatosis is becoming a major risk factor for hepatocellular carcinoma (HCC). Undertaken molecular events during the progression of steatosis to liver cancer are thus under intensive investigation. In this study, we demonstrated that high-fat diet potentiated mouse liver AKT2. Hepatic AKT2 hyperactivation through gain-of-function mutation of Akt2 (Akt2E17K) caused spontaneous hepatosteatosis, injury, inflammation, fibrosis, and eventually HCC in mice. AKT2 activation also exacerbated lipopolysaccharide and D-galactosamine hydrochloride-induced injury/inflammation and N-Nitrosodiethylamine (DEN)-induced HCC. A positive correlation between AKT2 activity and SCD1 expression was observed in human HCC samples. Activated AKT2 enhanced the production of monounsaturated fatty acid which was dependent on SREBP1 upregulation of SCD1. Blockage of active SREBP1 and ablation of SCD1 reduced steatosis, inflammation, and tumor burden in DEN-treated Akt2E17K mice. Therefore, AKT2 activation is crucial for the development of steatosis-associated HCC which can be treated with blockage of AKT2-SREBP1-SCD1 signaling cascade. [ABSTRACT FROM AUTHOR]

Background: Hepatocellular carcinoma (HCC) is the first cause of cancer in Egypt. Recently, HCC developed post direct-acting antivirals (DAAs) differ in some characteristics from those developed without DAAs exposure regarding the biological features and behavior of HCC. We aimed to assess the epidemiological, clinical, laboratory, and radiological findings besides the biological behavior of HCC patients post DAAs in comparison to HCC not exposed to DAAs. An analytic cross-sectional research was performed at the National Liver Institute which is a tertiary multidisciplinary HCC center. Subjects included hepatitis C virus patients and were allocated into two groups: group I included 2036 HCC cases post-DAA treatment and group II included 6338 HCC cases who did not receive DAAs. Subjects were examined to evaluate clinical, laboratory, and radiological findings. Tumor staging was done using the BCLC staging system. Results: Group II showed a more advanced Child–Pugh score, FIB-4 index, and MELD score than Group I (P = 0.001). The multiplicity of hepatic focal lesions was elevated in group I than in group II (P = 0.033). AFP level was significantly elevated in group I than in group II (p = 0.012). Portal vein invasion was significantly elevated in group I than in group II patients (P = 0.001). Extrahepatic spread of HCC was significantly elevated in group I than in group II (P = 0.001). Infiltrative lesions were significantly elevated in group I than in group II (P = 0.002). Conclusion: Our study detected that the behavior in HCC post DAAs treatment is more aggressive in respect of the number of lesions, PV invasion; local and distant metastasis, and serum AFP level than in patients unexposed to DAAs. Strict surveillance in cirrhotic patients treated with DAA should be followed according to the international guidelines for early diagnosis and treatment of HCC. [ABSTRACT FROM AUTHOR]

To examine the clinical outcomes of yttrium-90 (Y90) transarterial radioembolization (TARE) for primary hepatocellular carcinoma (HCC) through the evaluation of a 5-year institutional experience. This retrospective study evaluated 88 consecutive patients with primary HCC receiving Y90 TARE treatment at an academic medical center from 2017 to 2021. Disease distribution was bilobar in 60.2% of patients with an average lesion diameter of 5.0 ± 3.4 cm and Barcelona Clinic Liver Cancer stage B or C in 77% of the participants. Clinical outcomes were elucidated by examination of complications, liver function tests, biochemical response, and radiographic response. Objective response ratio (ORR) and progression-free survival (PFS) were also calculated. The mean administered Y90 radiation dose was 127.8 ± 20.2 Gy. No significant complications or LFT elevations occurred post-therapy. Of the 73.9% of patients with α-fetoprotein-producing tumors, 67.8% experienced a complete or partial biochemical response 1 month post-treatment. The ORR was 83.3% on 6-month imaging and PFS was 9.6 ± 8.5 months. Functional outcomes (Eastern Cooperative Oncology Group) were maintained or improved in 79.6% and 76.1% of patients by 6 months and 1 year post-treatment, respectively. The mean survival was 14.7 ± 12.1 months. At 6 months post-treatment, 77.3% of patients were downstaged to or maintained Milan criteria, which was sustained for 74.4% and 70.0% of patients 1 year and 2 years after treatment, respectively. Y90-TARE is a safe and effective therapy for primary HCC. Enduring outcomes further act as a realistic bridge to liver transplantation, with a majority of patients maintaining Milan criteria and preserving their functional status long term. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) treatment often requires transarterial chemoembolization (TACE). However, TACE efficacy is controversial in the presence of portal vein thrombosis (PVT). Although transarterial radioembolization (TARE) benefit was previously documented in PVT, neither the objective tumor response (OTR) after TARE with Iodine-131-lipiodol (131I-lipiodol) nor the PVT effect on the results of locoregional therapies was accurately measured in prospective clinical trials. The aim of this study was to compare OTR and survival obtained by TARE with 131I-lipiodol versus TACE in patients with cirrhosis and HCC, as well as between those with and without PVT. 33 patients were included, from whom 38 tumors were assessed. OTR was quantified by a special algorithm to measure hypervascular HCC tissue. 19 tumors received each therapy. Nine subjects (27%) had PVT, most of them in the TARE group (p = 0.026). Mean OTR according to the tumor volumes was 24.2% ± 56% after TARE and 32.8% ± 48.9% after TACE, with no difference between the treatments (p = 0.616). Similar values were also observed between those with and without PVT (p = 0.704). Mean survival was 340 days and did not differ between the two treatments (p = 0.596), but was 194 days in PVT cases (p = 0.007). This is the first study in which OTR obtained by TARE with 131I-lipiodol is accurately measured. Additionally, PVT impact on survival after TARE and TACE was precisely documented. Although the TARE group had more PVT subjects (who had shorter survival), TARE and TACE achieved similar OTR and OS rates. [ABSTRACT FROM AUTHOR]

The study was designed to evaluate microvascular invasion (MVI) using three-dimensional (3D) morphological indicators prior to surgery. This retrospective study included 156 patients with hepatocellular carcinoma (HCC) at our hospital from 2017 to 2018. Through thin-layer CT scanning and 3D reconstruction, the tumor surface inclination angles can be quantitatively analyzed to determine the surface irregularity rate (SIR), which serves as a comprehensive assessment method for tumor irregularity based on preoperative 3D morphological evaluation. Univariate and multivariate logistic regression analyses were employed to investigate the correlation with MVI. The SIR was related to MVI (OR: 10.667, P < 0.001). Multivariate logistic regression analysis showed that the SIR was an independent risk factor for MVI. The area under the receiver operating characteristic curve (ROC) of prediction model composed of the morphological indicator SIR was 0.831 (95% confidence interval: 0.759–0.895). The preoperative 3D morphological indicator SIR of a tumor is an accurate predictor of MVI, providing a valuable tool in clinical decision-making. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) is one of the most common malignancies and tends to have a poor prognosis due to its insidious onset, difficulty in early diagnosis, and limited treatment options. Tubulin epsilon and delta complex 2 (TEDC2), also known as C16orf59, is implicated in maintaining centriole stability, but the involvement of TEDC2 in HCC remains unknown. This study aimed to investigate the expression profile and potential mechanisms of TEDC2 in HCC. Multiple RNA sequencing datasets were screened for differentially expressed genes in HCC, and the prognosis-related gene, TEDC2, was further screened as a target gene in this study. The expression of TEDC2 in public datasets and clinical specimens was analyzed, and the involvement of TEDC2 in HCC was investigated by bioinformatic analysis and in vitro experiments. TEDC2 levels were elevated in HCC compared to healthy livers. Overexpression of TEDC2 was positively correlated with pathologic stage and histologic grade. In addition, TEDC2 was found to be an independent prognostic predictor. An excellent prognostic model of HCC was successfully constructed with TEDC2 in combination with the TNM stage. Bioinformatic analysis revealed that overexpression of TEDC2 might be associated with impaired tumor immunity in HCC, as evidenced by increased infiltration of T helper 2 (Th2) cells and reduced infiltration of cytotoxic cells. Further studies showed that TP53 mutations regulated TEDC2 expression, and TEDC2 was significantly associated with drug sensitivity. Moreover, overexpression of TEDC2 promoted cell metastasis and proliferation in vitro. These findings initially suggested a crucial effect of TEDC2 overexpression on HCC tumor progression, suggesting its potential as a novel prognostic and therapeutic target in HCC. [ABSTRACT FROM AUTHOR]

Transarterial radioembolization (TARE) is one of the most promising therapeutic options for hepatic masses. Radiomics features, which are quantitative numeric features extracted from medical images, are considered to have potential in predicting treatment response in TARE. This article aims to provide meta-analytic evidence and critically appraise the methodology of radiomics studies published in this regard. A systematic search was performed on PubMed, Scopus, Embase, and Web of Science. All relevant articles were retrieved, and the characteristics of the studies were extracted. The Radiomics Quality Score and Checklist for Evaluation of Radiomics Research were used to assess the methodologic quality of the studies. Pooled sensitivity, specificity, and area under the receiver operating characteristic curve in predicting objective response were determined. The systematic review included 15 studies. The average Radiomics Quality Score of these studies was 11.4 ± 2.1, and the average Checklist for Evaluation of Radiomics Research score was 33± 6.7. There was a notable correlation (correlation coefficient = 0.73) between the two metrics. Adherence to quality measures differed considerably among the studies and even within different components of the same studies. The pooled sensitivity and specificity of the radiomics models in predicting complete or partial response were 83.5% (95% confidence interval 76%-88.9%) and 86.7% (95% confidence interval 78%-92%), respectively. Radiomics models show great potential in predicting treatment response in TARE of hepatic lesions. However, the heterogeneity seen between the methodologic quality of studies may limit the generalizability of the results. Future initiatives should aim to develop radiomics signatures using multiple external datasets and adhere to quality measures in radiomics methodology. [ABSTRACT FROM AUTHOR]

Liver transplantation is the ideal treatment of choice for Familial amyloid polyneuropathy (FAP). It is known that during transplantation surgery, this explant liver which will be removed from amyloid patient can be used as a domino graft for another suitable recipient. Even after successful results of domino liver transplantation in deceased donation setting this procedure is always seen with a fear of putting both the recipients at risk due to technical challenge. With living donor as the liver donor for the amyloid patient, the challenges faced are even higher. Only few centres have done similar surgeries and there are no standard guidelines for the same. The anatomical prerequisites, technique, and indications of domino orthotopic liver transplant (D-OLT) in live donation settling are still evolving. We here report a case of live donor liver transplant from a 38 year old with a Right lobe graft for a 40 year old with FAP along with D-OLT for a 52 year old with HBV related decompensated chronic liver disease with HCC. We have described the technical challenges and learnings in our first case which is one of few cases done in the Indian Subcontinent. [ABSTRACT FROM AUTHOR]