Search

Activated Wnt/β-catenin pathway is a key genetic event in liver cancer development. Solute carrier (SLC) transporters are promising drug targets. Here, we identify SLC13A3 as a drug-targetable effector downstream of β-catenin in liver cancer. SLC13A3 expression is elevated in human liver cancer samples with gain of function (GOF) mutant CTNNB1, the gene encoding β-catenin. Activation of β-catenin up-regulates SLC13A3, leading to intracellular accumulation of endogenous SLC13A3 substrates. SLC13A3 is identified as a low-affinity transporter for glutathione (GSH). Silencing of SLC13A3 downregulates the leucine transporter SLC7A5 via c-MYC signaling, leading to leucine depletion and mTOR inactivation. Furthermore, silencing of SLC13A3 depletes GSH and induces autophagic ferroptosis in β-catenin-activated liver cancer cells. Importantly, both genetic inhibition of SLC13A3 and a small molecule SLC13A3 inhibitor suppress β-catenin-driven hepatocarcinogenesis in mice. Altogether, our study suggests that SLC13A3 could be a promising therapeutic target for treating human liver cancers with GOF CTNNB1 mutations.

Background and aimsSecond-generation direct-acting antivirals (2G DAA) to cure HCV have led to dramatic clinical improvements. HCV-associated hepatocellular carcinoma (HCC), however, remains common. Impaired immune tumor surveillance may play a role in HCC development. Our cohort evaluated the effects of innate immune types and clinical variables on outcomes including HCC.MethodsParticipants underwent full HLA class I/KIR typing and long-term HCV follow-up.ResultsA total of 353 HCV+ participants were followed for a mean of 7 years. Cirrhosis: 25% at baseline, developed in 12% during follow-up. 158 participants received 2G DAA therapy. HCC developed without HCV therapy in 20 subjects, 24 HCC after HCV therapy, and 10 of these after 2G DAA. Two predictors of HCC among 2G DAA-treated patients: cirrhosis (OR, 10.0, p = 0.002) and HLA/KIR profiles predicting weak natural killer (NK) cell-mediated immunity (NK cell complementation groups 6, 9, 11, 12, OR of 5.1, p = 0.02). Without 2G DAA therapy: cirrhosis was the main clinical predictor of HCC (OR, 30.8, p < 0.0001), and weak NK-cell-mediated immunity did not predict HCC.ConclusionCirrhosis is the main risk state predisposing to HCC, but weak NK-cell-mediated immunity may predispose to post-2G DAA HCC more than intermediate or strong NK-cell-mediated immunity.

BACKGROUND: Serum AFP-L3%, AFP, and DCP are useful biomarkers for HCC detection, but their utility in assessing treatment response remains unknown. We aim to evaluate the accuracy of a biomarker model in the detection of posttreatment viable tumors. METHODS: For model derivation, recipients with HCC undergoing liver transplant from 2018 to 2022 who had biomarkers collected within 3 months before transplant were included. We developed a generalized linear model for detecting posttreatment viable tumors with the 3 biomarkers as covariates, which we termed the LAD Score. An independent cohort of 117 patients with HCC was used for external validation. RESULTS: Among 205 recipients of transplant, 70.2% had evidence of viable tumor on explant. The median LAD score was higher among patients with viable versus nonviable tumors (1.06 vs. 0.465, p < 0.001). The LAD score had a sensitivity of 55.6% and a specificity of 85.1% at the cutoff of 0.927, which was more accurate than imaging for detecting posttreatment viable tumors (AUROC 0.736 vs. 0.643, respectively; p = 0.045). The superior performance of the LAD score over imaging is primarily driven by its greater accuracy in detecting tumors

BACKGROUND AND AIMS: Despite the substantial impact of environmental factors, individuals with a family history of liver cancer have an increased risk for HCC. However, genetic factors have not been studied systematically by genome-wide approaches in large numbers of individuals from European descent populations (EDP). APPROACH AND RESULTS: We conducted a 2-stage genome-wide association study (GWAS) on HCC not affected by HBV infections. A total of 1872 HCC cases and 2907 controls were included in the discovery stage, and 1200 HCC cases and 1832 controls in the validation. We analyzed the discovery and validation samples separately and then conducted a meta-analysis. All analyses were conducted in the presence and absence of HCV. The liability-scale heritability was 24.4% for overall HCC. Five regions with significant ORs (95% CI) were identified for nonviral HCC: 3p22.1, MOBP , rs9842969, (0.51, [0.40-0.65]); 5p15.33, TERT , rs2242652, (0.70, (0.62-0.79]); 19q13.11, TM6SF2 , rs58542926, (1.49, [1.29-1.72]); 19p13.11 MAU2 , rs58489806, (1.53, (1.33-1.75]); and 22q13.31, PNPLA3 , rs738409, (1.66, [1.51-1.83]). One region was identified for HCV-induced HCC: 6p21.31, human leukocyte antigen DQ beta 1, rs9275224, (0.79, [0.74-0.84]). A combination of homozygous variants of PNPLA3 and TERT showing a 6.5-fold higher risk for nonviral-related HCC compared to individuals lacking these genotypes. This observation suggests that gene-gene interactions may identify individuals at elevated risk for developing HCC. CONCLUSIONS: Our GWAS highlights novel genetic susceptibility of nonviral HCC among European descent populations from North America with substantial heritability. Selected genetic influences were observed for HCV-positive HCC. Our findings indicate the importance of genetic susceptibility to HCC development.

We report a multi-ancestry genome-wide association study on liver cirrhosis and its associated endophenotypes, alanine aminotransferase (ALT) and γ-glutamyl transferase. Using data from 12 cohorts, including 18,265 cases with cirrhosis, 1,782,047 controls, up to 1 million individuals with liver function tests and a validation cohort of 21,689 cases and 617,729 controls, we identify and validate 14 risk associations for cirrhosis. Many variants are located near genes involved in hepatic lipid metabolism. One of these, PNPLA3 p.Ile148Met, interacts with alcohol intake, obesity and diabetes on the risk of cirrhosis and hepatocellular carcinoma (HCC). We develop a polygenic risk score that associates with the progression from cirrhosis to HCC. By focusing on prioritized genes from common variant analyses, we find that rare coding variants in GPAM associate with lower ALT, supporting GPAM as a potential target for therapeutic inhibition. In conclusion, this study provides insights into the genetic underpinnings of cirrhosis.

This study investigates Bacillus Calmette-Guérin (BCG) as a potential treatment for hepatocellular carcinoma (HCC), a condition often associated with unfavorable treatment outcomes. Exploiting BCGs recognized immune-boosting properties, preclinical trials are conducted using HCC mice, with a single subcutaneous dose of BCG administered post-tumor formation. Results indicate that BCG treatment effectively diminishes tumor burden and extends survival in both male and female HCC mice. Positive influences on hepatic fibrosis and metabolism are observed, leading to a reduction in lipid levels. Spatial analysis underscores BCGs tumor-specific effects, inducing the enrichment of metabolic pathways and inhibiting various cancer-related pathways. Furthermore, BCG promotes immune cell infiltration, including CD4+, CD8+ T cells, and M1 macrophages, in both v-akt murine thymoma viral oncogene homolog 1(AKT)/neutoblastoma RAS viral oncogene homolog (RAS) and β-catenin positive HCC models. Interestingly, blocking T cells, trained immunity, and Interferon-γ (IFN-γ) function reverses BCGs anti-HCC effects. In conclusion, BCG emerges as a promising treatment option for HCC, characterized by a favorable safety profile and efficacy in inhibiting fibrosis, improving metabolism, and engaging both trained immunity and T cells in therapeutic mechanisms.

The MYC oncogene is often dysregulated in human cancer, including hepatocellular carcinoma (HCC). MYC is considered undruggable to date. Here, we comprehensively identify genes essential for survival of MYChigh but not MYClow cells by a CRISPR/Cas9 genome-wide screen in a MYC-conditional HCC model. Our screen uncovers novel MYC synthetic lethal (MYC-SL) interactions and identifies most MYC-SL genes described previously. In particular, the screen reveals nucleocytoplasmic transport to be a MYC-SL interaction. We show that the majority of MYC-SL nucleocytoplasmic transport genes are upregulated in MYChigh murine HCC and are associated with poor survival in HCC patients. Inhibiting Exportin-1 (XPO1) in vivo induces marked tumor regression in an autochthonous MYC-transgenic HCC model and inhibits tumor growth in HCC patient-derived xenografts. XPO1 expression is associated with poor prognosis only in HCC patients with high MYC activity. We infer that MYC may generally regulate and require altered expression of nucleocytoplasmic transport genes for tumorigenesis.

Hepatocellular carcinoma (HCC) is the fifth leading cause of cancer-related mortality worldwide. Programmed cell death ligand-1 (PD-L1) is an immune checkpoint protein that binds to programmed cell death-1 (PD-1), which is expressed in activated T cells and other immune cells and has been employed in cancer therapy, including HCC. Recently, PD-L1 overexpression has been documented in treatment-resistant cancer cells. Sorafenib is a multikinase inhibitor and the only FDA-approved treatment for advanced HCC. However, several patients exhibit resistance to sorafenib during treatment. This study aimed to assess the effect of glucose deprivation on PD-L1 expression in HCC cells. We used PD-L1-overexpressing HepG2 cells and IFN-γ-treated SK-Hep1 cells to explore the impact of glycolysis on PD-L1 expression. To validate the correlation between PD-L1 expression and glycolysis, we analyzed data from The Cancer Genome Atlas (TCGA) and used immunostaining for HCC tissue analysis. Furthermore, to modulate PD-L1 expression, we treated HepG2, SK-Hep1, and sorafenib-resistant SK-Hep1R cells with rapamycin. Here, we found that glucose deprivation reduced PD-L1 expression in HCC cells. Additionally, TCGA data and immunostaining analyses confirmed a positive correlation between the expression of hexokinase II (HK2), which plays a key role in glucose metabolism, and PD-L1. Notably, rapamycin treatment  decreased the expression of PD-L1 and HK2 in both high PD-L1-expressing HCC cells and sorafenib-resistant cells. Our results suggest that the modulation of PD-L1 expression by glucose deprivation may represent a strategy to overcome PD-L1 upregulation in patients with sorafenib-resistant HCC.

BackgroundHeterogeneity of hepatocellular carcinoma (HCC) presents significant challenges for therapeutic strategies and necessitates combinatorial treatment approaches to counteract suppressive behavior of tumor microenvironment and achieve improved outcomes. Here, we employed cytokines to induce memory-like behavior in natural killer (NK) cells, thereby enhancing their cytotoxicity against HCC. Additionally, we evaluated the potential benefits of combining sorafenib with this newly developed memory-like NK cell (pNK) immunochemotherapy in a preclinical model.MethodsHCC tumors were grown in SD rats using subcapsular implantation. Interleukin 12/18 cytokines were supplemented to NK cells to enhance cytotoxicity through memory activation. Tumors were diagnosed using MRI, and animals were randomly assigned to control, pNK immunotherapy, sorafenib chemotherapy, or combination therapy groups. NK cells were delivered locally via the gastrointestinal tract, while sorafenib was administered systemically. Therapeutic responses were monitored with weekly multi-parametric MRI scans over three weeks. Afterward, tumor tissues were harvested for histopathological analysis. Structural and functional changes in tumors were evaluated by analyzing MRI and histopathology data using ANOVA and pairwise T-test analyses.ResultsThe tumors were allowed to grow for six days post-cell implantation before treatment commenced. At baseline, tumor diameter averaged 5.27 mm without significant difference between groups (p = 0.16). Both sorafenib and combination therapy imposed greater burden on tumor dimensions compared to immunotherapy alone in the first week. By the second week of treatment, combination therapy had markedly expanded its therapeutic efficacy, resulting in the most significant tumor regression observed (6.05 ± 1.99 vs. 13.99 ± 8.01 mm). Histological analysis demonstrated significantly improved cell destruction in the tumor microenvironment associated with combination treatment (63.79%). Interestingly, we observed fewer viable tumor regions in the sorafenib group (38.9%) compared to the immunotherapy group (45.6%). Notably, there was a significantly higher presence of NK cells in the tumor microenvironment with combination therapy (34.79%) compared to other groups (ranging from 2.21 to 26.50%). Although the tumor sizes in the monotherapy groups were similar, histological analysis revealed a stronger response in pNK cell immunotherapy group compared to the sorafenib group.ConclusionsExperimental results indicated that combination therapy significantly enhanced treatment response, resulting in substantial tumor growth reduction in alignment with histological analysis.

BackgroundProgression to cirrhosis in non-alcoholic steatohepatitis (NASH) is associated with a decrease in liver fat. However, the prognostic significance of liver fat content in NASH-related significant fibrosis and cirrhosis is unclear.AimTo investigate the risk of decompensation, hepatocellular carcinoma (HCC) and mortality stratified by liver fat content in NASH-related significant fibrosis and cirrhosis.MethodsIn this meta-analysis of individual participant data, 456 patients with both magnetic resonance elastography (MRE) and MRI-derived protein density fat fraction (MRI-PDFF) were enrolled, and 296 patients with longitudinal follow-up were analysed. MRE combined with fibrosis-4 (MEFIB-index), and MRI-PDFF were used to measure liver fibrosis and fat, respectively. MEFIB-negative, MEFIB-positive+ MRI-PDFF ≥5% and MEFIB-positive+ MRI-PDFF

Purpose To assess adherence to the US Liver Imaging Reporting and Data System (LI-RADS) recommendations for hepatocellular carcinoma (HCC) surveillance and associated patient-level factors in a vulnerable, diverse patient sample. Materials and Methods The radiology report database was queried retrospectively for patients who underwent US LI-RADS-based surveillance examinations at a single institution between June 1, 2020, and February 28, 2021. Initial US and follow-up liver imaging were included. Sociodemographic and clinical data were captured from electronic medical records. Adherence to radiologist recommendation was defined as imaging (US, CT, or MRI) follow-up in 5-7 months for US-1, imaging follow-up in 3-6 months for US-2, and CT or MRI follow-up in 2 months for US-3. Descriptive analysis and multivariable modeling that adjusted for age, sex, race, and time since COVID-19 pandemic onset were performed. Results Among 936 patients, the mean age was 59.1 years; 531 patients (56.7%) were male and 544 (58.1%) were Asian or Pacific Islander, 91 (9.7%) were Black, 129 (13.8%) were Hispanic, 147 (15.7%) were White, and 25 (2.7%) self-reported as other race. The overall adherence rate was 38.8% (95% CI: 35.7, 41.9). The most common liver disease etiology was hepatitis B (60.6% [657 of 936 patients]); 19.7% of patients (183 of 936) had current or past substance use disorder, and 44.8% (416 of 936) smoked. At adjusted multivariable analysis, older age (odds ratio [OR], 1.20; P = .02), male sex (OR, 1.62; P = .003), hepatology clinic attendance (OR, 3.81; P < .001), and recent prior US examination (OR, 2.44; P < .001) were associated with full adherence, while current smoking (OR, 0.39; P < .001) was negatively associated. Conclusion Adherence to HCC imaging surveillance was suboptimal, despite US LI-RADS implementation. Keywords: Liver, Ultrasound, Screening, Abdomen/GI, Cirrhosis, Metabolic Disorders, Socioeconomic Issues Supplemental material is available for this article. © RSNA, 2024.

Liver cancer remains a challenge of global health, being the 4th leading cause of cancer death worldwide. Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer, and is usually precipitated by chronic viral infections (hepatitis B and C), non-alcoholic steatohepatitis, heavy alcohol use, and other factors which may lead to chronic inflammation and cirrhosis of the liver. There have been significant advances in the systemic treatment options for HCC over the past decades, with several approvals of both immune checkpoint inhibitors and tyrosine kinase inhibitors in patients with preserved liver function. These advances have led to improvement in survival outcomes, with expected survival of greater than 18 months, in those with sensitive tumors, adequate liver function, and those functionally fit to receive sequential therapies. Several ongoing and promising trials are now evaluating combinational strategies with novel systemic agents and combinations of systemic therapy with locoregional therapy. In view of these trials, further advances in the treatment of HCC are foreseen in the near future.

BackgroundHepatocellular carcinoma (HCC) is a common liver malignancy with limited treatment options. Previous studies expressed the potential synergy of sorafenib and NK cell immunotherapy as a promising approach against HCC. MRI is commonly used to assess response of HCC to therapy. However, traditional MRI-based metrics for treatment efficacy are inadequate for capturing complex changes in the tumor microenvironment, especially with immunotherapy. In this study, we investigated potent MRI radiomics analysis to non-invasively assess early responses to combined sorafenib and NK cell therapy in a HCC rat model, aiming to predict multiple treatment outcomes and optimize HCC treatment evaluations.MethodsSprague Dawley (SD) rats underwent tumor implantation with the N1-S1 cell line. Tumor progression and treatment efficacy were assessed using MRI following NK cell immunotherapy and sorafenib administration. Radiomics features were extracted, processed, and selected from both T1w and T2w MRI images. The quantitative models were developed to predict treatment outcomes and their performances were evaluated with area under the receiver operating characteristic (AUROC) curve. Additionally, multivariable linear regression models were constructed to determine the correlation between MRI radiomics and histology, aiming for a noninvasive evaluation of tumor biomarkers. These models were evaluated using root-mean-squared-error (RMSE) and the Spearman correlation coefficient.ResultsA total of 743 radiomics features were extracted from T1w and T2w MRI data separately. Subsequently, a feature selection process was conducted to identify a subset of five features for modeling. For therapeutic prediction, four classification models were developed. Support vector machine (SVM) model, utilizing combined T1w + T2w MRI data, achieved 96% accuracy and an AUROC of 1.00 in differentiating the control and treatment groups. For multi-class treatment outcome prediction, Linear regression model attained 85% accuracy and an AUC of 0.93. Histological analysis showed that combination therapy of NK cell and sorafenib had the lowest tumor cell viability and the highest NK cell activity. Correlation analyses between MRI features and histological biomarkers indicated robust relationships (r = 0.94).ConclusionsOur study underscored the significant potential of texture-based MRI imaging features in the early assessment of multiple HCC treatment outcomes.

Objectives: To investigate associations between tissue diffusion, stiffness, and different tumor microenvironment features in resected hepatocellular carcinoma (HCC). Methods: Seventy-two patients were prospectively included for preoperative magnetic resonance (MR) diffusion-weighted imaging and MR elastography examination. The mean apparent diffusion coefficient (ADC) and stiffness value were measured on the central three slices of the tumor and peri-tumor area. Cell density, tumor-stroma ratio (TSR), lymphocyte-rich HCC (LR-HCC), and CD8 + T cell infiltration were estimated in resected tumors. The interobserver agreement of MRI measurements and subjective pathological evaluation was assessed. Variables influencing ADC and stiffness were screened with univariate analyses, and then identified with multivariable linear regression. The potential relationship between explored imaging biomarkers and histopathological features was assessed with linear regression after adjustment for other influencing factors. Results: Seventy-two patients (male/female: 59/13, mean age: 56 ± 10.2 years) were included for analysis. Inter-reader agreement was good or excellent regarding MRI measurements and histopathological evaluation. No correlation between tumor ADC and tumor stiffness was found. Multivariable linear regression confirmed that cell density was the only factor associated with tumor ADC (Estimate = −0.03, p = 0.006), and tumor-stroma ratio was the only factor associated with tumor stiffness (Estimate = −0.18, p = 0.03). After adjustment for fibrosis stage (Estimate = 0.43, p < 0.001) and age (Estimate = 0.04, p < 0.001) in the multivariate linear regression, intra-tumoral CD8 + T cell infiltration remained a significant factor associated with peri-tumor stiffness (Estimate = 0.63, p = 0.02). Conclusions: Tumor ADC surpasses tumor stiffness as a biomarker of cellularity. Tumor stiffness is associated with tumor-stroma ratio and peri-tumor stiffness might be an imaging biomarker of intra-tumoral immune microenvironment. Clinical relevance statement: Tissue stiffness could potentially serve as an imaging biomarker of the intra-tumoral immune microenvironment of hepatocellular carcinoma and aid in patient selection for immunotherapy. Key Points: Apparent diffusion coefficient reflects cellularity of hepatocellular carcinoma. Tumor stiffness reflects tumor-stroma ratio of hepatocellular carcinoma and is associated with tumor-infiltrating lymphocytes. Tumor and peri-tumor stiffness might serve as imaging biomarkers of intra-tumoral immune microenvironment. [ABSTRACT FROM AUTHOR]

Background: Diacylglycerol O-acyltransferase 2 (DGAT2) synthesizes triacylglycerol (TG) from diacylglycerol; therefore, DGAT2 is considered as a therapeutic target for steatosis. However, the consequence of inhibiting DGAT2 is not fully investigated due to side effects including lethality and lipotoxicity. In this article, we observed the role of DGAT2 in hepatocarcinoma. Methods: The role of DGAT2 is analyzed via loss-of-function assay. DGAT2 knockdown (KD) and inhibitor treatment on HepG2 cell line was analyzed. Cumulative analysis of cell metabolism with bioinformatic data were assessed, and further compared with different cohorts of liver cancer patients and non-alcoholic fatty liver disease (NAFLD) patients to elucidate how DGAT2 is regulating cancer metabolism. Results: Mitochondrial function is suppressed in DGAT2 KD HepG2 cell along with the decreased lipid droplets. In the aspect of the cancer, DGAT2 KD upregulates cell proliferation. Analyzing transcriptome of NAFLD and hepatocellular carcinoma (HCC) patients highlights negatively correlating expression patterns of 73 lipid-associated genes including DGAT2. Cancer patients with the lower DGAT2 expression face lower survival rate. DGAT2 KD cell and patients' transcriptome show downregulation in estrogen- related receptor alpha (ESRRA) via integrated system for motif activity response analysis (ISMARA), with increased dimerization with corepressor prospero homeobox 1 (PROX1). Conclusion: DGAT2 sustains the stability of mitochondria in hepatoma via suppressing ESRRA-PROX1 transcriptional network and hinders HCC from shifting towards glycolytic metabolism, which lowers cell proliferation. [ABSTRACT FROM AUTHOR]

Objective To investigate the effect and mechanism of cinobufotalin in inhibiting hepatocellular carcinoma (HCC) metastasis by regulating epithelial-mesenchymal transition (EMT). Methods A total of 36 male BALB/c nude mice, aged 6 weeks，were given injection of MHCC97H cells via the caudal vein to establish a model of HCC lung metastasis, and then the mice were randomly divided into high-and low-dose cinobufotalin groups and control group. Since the day of modeling, the mice in the high-and low-dose cinobufotalin groups were given intraperitoneal injection of cinobufotalin at a dose of 120 µL/kg and 60 µL/kg, respectively, and those in the control group were given intraperitoneal injection of normal saline, twice a week. After 8 weeks, HE staining was performed for lung tissue to measure the lung metastasis rate of HCC. MHCC97H cells were treated with high-dose (2.5 µL/mL) or low-dose (5 µL/mL) cinobufotalin for 24 hours, and wound healing assay, RT-PCR, and Western blot were used to measure cell migration ability and the expression of EMT-related molecules. MHCC97H cells were induced in a simulated hypoxic environment with CoCl2 incubation, with high- and low-dose cinobufotalin added for intervention, and wound healing assay and Western blot were used to investigate the effect of cinobufotalin on cell migration ability and EMT induced by hypoxia. Transcriptome analysis was used to investigate the effect mechanism of cinobufotalin on MHCC97H cells, and Western blot was used to observe the effect of cinobufotalin on the expression levels of protein kinase B (AKT) and phosphorylated AKT (P-AKT) in MHCC97H cells. A oneway analysis of variance was used for comparison of continuous data between multiple groups, and the least significant difference ttest was used for further comparison between two groups； the independent-samples t test was used for comparison of categorical data between two groups. Results Compared with the control group, the cinobufotalin group had a significant reduction in the lung metastasis rate of HCC. Compared with the control group, cinobufotalin intervention reduced the wound healing rate of MHCC97H cells, upregulated the expression of epithelial-type molecules (t=2.860，P<0.05), and downregulated the expression of EMT transcription factors (EMT-TFs) and mesenchymal molecules (t=3.545，2.022，2.852, and 2.341, all P<0.05). Hypoxia induction upregulated the wound healing rate of MHCC97H cells and the expression levels of mesenchymal molecules and EMT-TFs (P<0.05), and cinobufotalin intervention reversed EMT change and inhibited wound healing (P<0.05). The transcriptome analysis of MHCC97H cells showed significant gene differences between the cinobufotalin group and the control group, and cinobufotalin mainly affected the expression of genes associated with tumor, metabolism, immunity, and signal transduction, with the largest number of differentially expressed genes in the AKT signal transduction pathway. Further measurement showed that cinobufotalin intervention downregulated the expression levels of AKT, P-AKT, and P-AKT/AKT in MHCC97H cells (t=2.434，3.401, and 2.258, all P<0.05). Conclusion Cinobufotalin can inhibit the metastasis of HCC, especially hypoxia-induced HCC metastasis, and regulation of EMT mediated by the AKT signal transduction pathway in HCC cells might be one of its mechanisms of action. [ABSTRACT FROM AUTHOR]

Objective To investigate the effect of AU-rich element RNA-binding factor 1 (AUF1) on the proliferation, apoptosis, and migration abilities of hepatocellular carcinoma (HCC) cells and possible mechanisms, and to clarify the role and molecular mechanism of AUF1 in the progression of HCC. Methods The UALCAN and TCGA-HCC databases were used to analyze the expression of AUF1 in pan-cancer and investigate the association of the expression level of AUF1 with the clinicopathological features and prognosis of HCC patients. CCK-8 assay, cell apoptosis assay, and Transwell chamber assay were used to investigate the function of AUF1 at the cellular level, and RNA-seq assay was used to investigate transcriptome changes in HCC cells after AUF1 knockdown. The t-test was used for comparison of continuous data between two groups； the Kaplan-Meier method was used to plot survival curves, and the log-rank test was used for comparison of survival rates. Results There were abnormal mRNA and protein expression levels of AUF1 in various tumor tissues compared with normal tissue (P<0.05). The mRNA expression level of AUF1 was positively correlated with the degree of HCC malignancy and the poor prognosis of early-stage HCC (P<0.05). Compared with the control group, the overexpression of exogenous AUF1 in HCC cells promoted the proliferation of HCC cells and inhibited the apoptosis and migration of HCC cells, while AUF1 knockdown inhibited HCC cell proliferation and promoted the apoptosis and migration of HCC cells. The RNA-seq analysis showed that AUF1 knockdown mainly affected the Wnt/β -catenin pathway and downregulated the protein expression level of β-catenin. Conclusion The abnormal expression of AUF1 is associated with the prognosis of early-stage HCC, and AUF1 may exert an oncogenic effect by activating the Wnt signaling pathway. [ABSTRACT FROM AUTHOR]

Objective To investigate the expression of disulfidptosis-related genes in hepatocellular carcinoma (HCC) and the prognostic value of disulfidptosis in HCC， to construct a prognostic model， and to analyze its impact on the biological processes of HCC and sorafenib resistance. Methods The TCGA-LIHC database was used to collect the mRNA expression profiles and corresponding clinical data of HCC patients， and the LASSO-Cox regression algorithm was used to construct a four-gene predictive model for prognosis in the TCGA cohort. The external datasets ICGC and GSE14520 were used to validate the prognostic efficacy of the model， and the Cancer Drug Sensitivity Genomics (GDSC) data were used to investigate the value of the disulfidptosis model in predicting sorafenib treatment response， and gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were used to investigate the biological functions of disulfidptosis-related genes. The independent-samples t test was used for comparison of continuous data between two groups， and the chi-square test was used for comparison of categorical data between two groups. The Kaplan-Meier curve and the log-rank test were used to evaluate the difference in prognosis， and univariate and multivariate Cox regression analyses were used to investigate whether risk score was an independent influencing factor for patient prognosis. Results The univariate Cox regression analysis in the TCGA cohort showed that seven known disulfidptosis-related genes were significantly associated with overall survival (OS) in HCC (all P<0.05) . The LASSO-Cox regression analysis was used to construct a prognostic model based on disulfidptosis-related genes (DRG) ， and the risk score RS-DRG was calculated as RSDRG= (0.061 6) ×GYS1 expression level+ (0.152 8) ×LRPPRC expression level+ (0.268 3) ×RPN1 expression level+ (0.183 5) × SLC7A11 expression level. The log-rank test showed that the patients with a high risk score based on the disulfidptosis model had a significantly lower OS than those with a low risk score (P<0.001) . Based on the results of the multivariate Cox regression analysis， risk score was an independent predictive factor for OS in both TCGA and ICGC cohorts (TCGA： hazard ratio [HR] =1.869，P=0.002； ICGC：HR=3.469，P=0.004) . The Spearman correlation analysis showed that RS-DRG was significantly positively correlated with the infiltration level of various immune cells (including B lymphocytes， CD4+ T lymphocytes， neutrophils， macrophages， and dendritic cells) in tumor microenvironment (all P<0.05) . The patients in the high-risk score group had a significantly lower IC50 value of sorafenib and were more sensitive to sorafenib (P<0.001) . The KEGG/GO enrichment analysis showed that the differentially expressed disulfidptosis-related genes were significantly enriched in various mitosis-related molecular functions. Conclusion This study constructed a novel prognostic model based on disulfidptosis-related genes， which has a potential clinical value in predicting the prognosis of HCC， and targeting disulfidptosis-related genes may provide a promising approach for HCC treatment. [ABSTRACT FROM AUTHOR]

Objective To investigate the efficacy and safety of microwave ablation (MWA) versus hepatic resection (HR) in the treatment of hepatocellular carcinoma (HCC) with liver cirrhosis using a meta-analysis. Methods This study was conducted according to the PRISMA guideline, with a PROSPERO registration number of CRD42024509185. PubMed, the Cochrane Library, EMBASE, Web of Science, CNKI, VIP, and Wanfang Data were searched for randomized controlled trials (RCTs) and cohort studies on MWA versus HR in the treatment of HCC with liver cirrhosis published up to November 2023, and Stata 12.0 was used to perform the meta-analysis. Results A total of 3 RCTs and 5 retrospective cohort studies were included, with 953 patients in total. The meta-analysis showed that there were no differences between MWA and HR in 1-, 2-, 3-, and 5-year overall survival (OS) rates (all P>0.05) and 1-, 2-, and 5-year recurrence rates (all P>0.05）. Compared with HR, MWA had a significantly higher 3-year recurrence rate (risk ratio [RR] =1.59, 95% confidence interval [CI] : 1.08—2.33, P=0.017) and significantly lower 1-, 3-, and 5-year disease-free survival (DFS) rates (1-year DFS rate: RR=0.94, 95%CI: 0.89—0.99, P=0.018, I² =0.0%； 3-year DFS rate: RR=0.84, 95%CI: 0.72—0.98, P=0.023, I² =25.4%；5-year DFS rate: RR=0.75, 95%CI: 0.58—0.98, P= 0.032, I² =34.6%）. However, subgroup analysis showed that there were no significant differences between MWA and HR in 1-, 2-, and 3-year OS rates and 1- and 3-year DFS rates in the RCT subgroup (all P>0.05）. Compared with HR, MWA had significantly better intraoperative blood loss (standardized mean difference [SMD] =−2.31, 95%CI: −2.64 to −1.97, P<0.001, I² =3.1%）, time of operation (SMD=−3.38, 95%CI: −4.05 to −2.71, P<0.001, I² =73.8%）, length of hospital stay (SMD=−2.54, 95%CI: −3.27 to −1.80, P<0.001, I² =92.8%）, adverse reactions (RR=0.42, 95%CI: 0.30—0.59, P<0.001, I² =0.0%）, and liver function (SMD= − 1.43, 95%CI: − 1.89—− 0.97, P<0.001）. Conclusion There are no significant differences between MWA and HR in local recurrence, DFS, and OS, but MWA tends to have a less intraoperative blood loss, a shorter time of operation, fewer adverse reactions, a less impact on liver function, and a shorter length of hospital stay. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors in clinical practice. Due to the lack of typical clinical manifestations in the early stage, most patients in China are in the advanced stage at the time of confirmed diagnosis and thus lose the opportunity for surgical resection, which leads to a poor prognosis. Therefore, it is necessary to explore related therapies for converting unresectable HCC into resectable HCC. In recent years, the improvement in local therapy such as transarterial interventional therapies and radiation therapy technology, together with the clinical application of new targeted therapies and immune checkpoint inhibitors, has brought new opportunities and challenges in the conversion therapy for advanced HCC, and local therapy combined with systemic therapy may have a good synergistic effect, improve the conversion rate of surgery. This article investigates the value of local therapy combined with systemic therapy in the conversion therapy for HCC, in order to provide a basis for the clinical treatment of unresectable HCC. [ABSTRACT FROM AUTHOR]

Due to the insidious onset and poor prognosis of primary liver cancer, most patients are found to have unresectable primary liver cancer at initial diagnosis. In recent years, with the advent of targeted therapy, immunotherapy, and local therapy, some patients with advanced liver cancer have achieved successful conversion and undergone radical surgical resection, but at the same time, such treatment has brought many issues, such as the identification of potential population for conversion, the selection of conversion regimen, the necessity and timing of surgical resection after conversion, and the necessity and duration of adjuvant therapy after conversion surgery. This article discusses the above problems in conversion therapy for liver cancer based on the author’s own experience. [ABSTRACT FROM AUTHOR]

Surgical resection remains the best approach for achieving long-term survival in patients with hepatocellular carcinoma （HCC）； however, due to the low early diagnosis rate of HCC patients in China, only 15%-20% of the patients are eligible for surgical resection at the time of initial diagnosis. Even for the patients undergoing surgery, the 5-year recurrence rate after surgery is as high as 50%-70%, resulting in an unsatisfactory prognosis. In recent years, the advances in systemic therapies, especially targeted therapy combined with immunotherapy, have not only extended the survival of patients with advanced liver cancer, but also promoted the application of systemic therapy in the earlier stages of HCC. On the one hand, the progress in systemic therapy has made conversion therapy a possible option for HCC, allowing a substantial number of patients with unresectable HCC at initial diagnosis to get the opportunity for surgical resection after downstaging and achieve a survival rate similar to those with resectable early-stage HCC at initial diagnosis； on the other hand, effective systemic therapy is being applied as neoadjuvant and adjuvant therapies for patients with resectable HCC, aiming to increase the R0 resection rate, reduce postoperative recurrence, and improve overall survival. Meanwhile, it should be clearly noted that although the advances in systemic therapy have significantly altered conventional surgical treatment paradigms, most clinical studies on conversion therapy, neoadjuvant therapy, and adjuvant therapy are small-scale phase II trials, with limited high-grade evidence from evidence-based medicine. It is important to select a reasonable therapeutic goal and develop an individualized treatment regimen based on the characteristics of tumor, and further explorations are needed to search for new biomarkers for predicting the efficacy of conversion therapy and perioperative treatment and identify the population with true benefits. [ABSTRACT FROM AUTHOR]

Simple Summary: Hepatocellular carcinoma (HCC) stands as a primary malignancy of the liver and represents a significant global health burden, particularly in regions where chronic hepatitis B and C infections prevail. Despite advancements in diagnostic techniques and therapeutic strategies, HCC continues to pose formidable challenges in clinical management due to its aggressive nature, frequent late-stage diagnosis, and metastasis to other organs. Although the incidence of metastasis to the diaphragm is low, this condition is one of few poor prognostic factors for HCC, making the early detection of diaphragm muscle involvement important in both primary and recurrent stages. The purpose of our study was to address two questions: (1) What symptoms or symptom clusters are reported among HCC patients with metastases to the diaphragm? (2) What risk factors for diaphragm muscle metastasis are present in HCC patients? Based on our findings, we conclude that the presence of hepatitis B and the localization of HCC cells in superior liver segments, particularly in the 8th liver segment, should be considered during the diagnostic process. Each patient in the reports presented with different symptoms, making it impossible to identify the leading symptom. The purpose of this study was to conduct a systematic review and meta-analysis of case reports presenting HCC spread to the diaphragm muscle and to determine possible risk factors for this condition. An extensive literature search was performed using the following electronic databases: MEDLINE, CINAHL, ScienceDirect, Google Scholar, and DOAJ. A total of 18 articles describing 27 hepatocellular carcinoma patients were included in this review. The presence of HCC cells in the superior liver segment is strongly associated with metastases to the diaphragm. Among the two types of diaphragm involvement by HCC cells, diaphragm infiltration occurs much more frequently than diaphragm adhesion. However, an HCC nodule in the 8th liver segment and a higher number of liver segments involved by HCC cells predispose patients to diaphragm adhesion. Hepatitis B is a risk factor for diaphragm metastases in recurrent HCC. The tumor diameter is not associated with HCC spread to the diaphragm muscle. We did not find specific symptoms reported by patients that could indicate HCC metastasis to the diaphragm muscle. The presence of hepatitis B and the localization of HCC cells in superior liver segments, especially in the 8th liver segment, should be take into consideration in the diagnostic process. [ABSTRACT FROM AUTHOR]

Background & aimsAlpha-fetoprotein (AFP) predicts hepatocellular carcinoma (HCC) recurrence after liver transplant (LT) but remains an imperfect biomarker. The role of DCP (des-gamma-carboxyprothrombin) and AFP-L3 (AFP bound to Lens culinaris agglutinin) in predicting HCC recurrence remains incompletely characterized. AFP-L3 and DCP could identify patients at high risk of post-transplant HCC recurrence and serve as liver transplant exclusion criteria to defer transplant until patients receive additional risk-reducing pre-transplant locoregional therapy.MethodsThis prospective cohort study included consecutive patients with HCC who underwent LT (within or down-staged to Milan criteria) between 2017 and 2022. Pre-transplant AFP, AFP-L3, and DCP measurements were obtained. The primary endpoint was the ability of biomarkers to predict HCC recurrence-free survival.ResultsThis cohort included 285 patients with a median age of 67 (IQR 63-71). At LT, median biomarker values were AFP 5.0 ng/ml (IQR 3.0-12.1), AFP-L3 6.7% (0.5-13.2), and DCP 1.0 ng/ml (0.3-2.8). Most (94.7%) patients received pre-LT locoregional therapy. After a median post-LT follow-up of 3.1 years, HCC recurrence was observed in 18 (6.3%) patients. AFP-L3 and DCP outperformed AFP with C-statistics of 0.81 and 0.86 respectively, compared with 0.74 for AFP. A dual-biomarker combination of AFP-L3 ≥15% and DCP ≥7.5 predicted 61.1% of HCC recurrences, whereas HCC only recurred in 7 of 265 (2.6%) patients not meeting this threshold. The Kaplan-Meier recurrence-free survival rate at 3 years post-LT was 43.7% for patients with dual-positive biomarkers compared to 97.0% for all others (p

PURPOSE: To evaluate the efficacy of combination therapy using transarterial chemoembolization with microwave ablation (MWA) therapy vs. MWA monotherapy for hepatocellular carcinomas (HCCs) >3 cm in size. METHODS: This two-arm retrospective observational study included patients with HCCs >3 cm who underwent either combination therapy (29 patients) or MWA monotherapy (35 patients) between 2014 and 2020. The treatment outcomes related to primary treatment efficacy, local tumor progression (LTP), tumor control rate, and overall survival were compared between each cohort. RESULTS: The technical success and primary efficacy were 96.56% and 100.00% in the combination therapy cohort, and 91.42% and 100.00% in the MWA cohort, respectively, over a mean follow-up period of 27.6 months. The 1- and 3-year rates of LTP-free survival were 78.57% and 69.56% in the combination therapy cohort, vs. 72.45% and 35.44% in the MWA cohort, respectively (P = 0.001). The overall progression-free survival was longer in the combination therapy cohort compared with the MWA cohort (median: 56.0 vs. 13.0 months; P = 0.017). With the incorporation of additional locoregional therapy, the overall survival rates were not significantly different, with 1- and 3-year overall survival rates of 100.00% and 88.71% in the combination therapy cohort and rates of 90.15% and 82.76% in the MWA cohort, respectively (P = 0.235). CONCLUSION: The combination therapy provided significantly longer upfront LTP-free survival in HCCs >3 cm when compared with the MWA treatment alone, albeit with similar local tumor control and overall survival rates when accounting for additional locoregional therapies.

Transarterial radioembolization (TARE) with yttrium-90 (90Y) microspheres has been widely adopted for the treatment of HCC. Recent advances in yttrium-90 (90Y) dosimetry have led to durable local responses. Radiation segmentectomy has become a viable alternative to thermal ablation for early-stage HCC (Barcelona Clinic Liver Cancer 0 and A) and has been commonly used as a bridge to transplant. TARE is also commonly used for downstaging to transplant using traditional lobar dosimetry and radiation segmentectomy techniques. Radiation lobectomy has a dual role in local tumor control and induction of contralateral liver lobe hypertrophy as a bridge to resection for patients with an inadequate future liver remnant. TARE continues to provide disease control for patients with limited vascular invasion and may be an alternative to systemic therapy for patients with localized advanced disease. The potential synergy between TARE and immunotherapy has been recognized, and prospective studies evaluating this combination are needed for patients with Barcelona Clinic Liver Cancer B and C HCC.

Liver tumors account for approximately 1%-2% of all pediatric malignancies, with the two most common tumors being hepatoblastoma (HB) and hepatocellular carcinoma (HCC). Previous Childrens Oncology Group studies have meaningfully contributed to the current understanding of disease pathophysiology and treatment, laying groundwork for the ongoing prospective international study of both HB and HCC. Future work is focused on elucidating the biologic underpinnings of disease to support an evolution in risk categorization, advancements in the multidimensional care required to treat these patients, and the discovery of novel therapies.

BackgroundData are scarce regarding the development of hepatic decompensation in patients with non-alcoholic fatty liver disease (NAFLD) with and without type 2 diabetes. We aimed to assess the risk of hepatic decompensation in people with NAFLD with and without type 2 diabetes.MethodsWe did a meta-analysis of individual participant-level data from six cohorts in the USA, Japan, and Turkey. Included participants had magnetic resonance elastography between Feb 27, 2007, and June 4, 2021. Eligible studies included those with liver fibrosis characterisation by magnetic resonance elastography, longitudinal assessment for hepatic decompensation and death, and included adult patients (aged ≥18 years) with NAFLD, for whom data were available regarding the presence of type 2 diabetes at baseline. The primary outcome was hepatic decompensation, defined as ascites, hepatic encephalopathy, or variceal bleeding. The secondary outcome was the development of hepatocellular carcinoma. We used competing risk regression using the Fine and Gray subdistribution hazard ratio (sHR) to compare the likelihood of hepatic decompensation in participants with and without type 2 diabetes. Death without hepatic decompensation was a competing event.FindingsData for 2016 participants (736 with type 2 diabetes; 1280 without type 2 diabetes) from six cohorts were included in this analysis. 1074 (53%) of 2016 participants were female with a mean age of 57·8 years (SD 14·2) years and BMI of 31·3 kg/m2 (SD 7·4). Among 1737 participants (602 with type 2 diabetes and 1135 without type 2 diabetes) with available longitudinal data, 105 participants developed hepatic decompensation over a median follow-up time of 2·8 years (IQR 1·4-5·5). Participants with type 2 diabetes had a significantly higher risk of hepatic decompensation at 1 year (3·37% [95% CI 2·10-5·11] vs 1·07% [0·57-1·86]), 3 years (7·49% [5·36-10·08] vs 2·92% [1·92-4·25]), and 5 years (13·85% [10·43-17·75] vs 3·95% [2·67-5·60]) than participants without type 2 diabetes (p

PurposeTo test the hypothesis that antitumoral immunity can be induced after cryoablation (cryo) of hepatocellular carcinoma (HCC) through coadministration of the immunostimulant CpG and an immune checkpoint (programmed cell death 1 [PD-1]) inhibitor.Materials and methodsSixty-three immunocompetent C57BL/6J mice were generated with 2 orthotopic HCC tumor foci: 1 for treatment and 1 to observe for antitumoral immunity. Tumors were treated with incomplete cryo alone or intratumoral CpG and/or a PD-1 inhibitor. The primary endpoint was death or when the following criteria for sacrifice were met: tumor > 1 cm (determined using ultrasound) or moribund state. Antitumoral immunity was assessed using flow cytometry and histology (tumor and liver) as well as enzyme-linked immunosorbent assay (serum). Analysis of variance was used for statistical comparisons.ResultsAt 1 week, the nonablated satellite tumor growth was reduced by 1.9-fold (P = .047) in the cryo + CpG group and by 2.8-fold (P = .007) in the cryo + CpG + PD-1 group compared with that in the cryo group. Compared with cryo alone, the time to tumor progression to endpoints was also prolonged for cryo + CpG + PD-1 and cryo + CpG mice, with log-rank hazard ratios of 0.42 (P = .031) and 0.27 (P < .001), respectively. Flow cytometry and histology showed increased cytotoxic T-cell infiltration (P = .002) and serum levels of the proinflammatory cytokine interferon-γ (P = .015) in tumors and serum of cryo + CpG mice compared with those in tumors and serum of mice treated with cryo alone. High serum levels of the anti-inflammatory cytokine tumor growth factor-β and the proangiogenesis chemokine C-X-C motif chemokine ligand 1 were correlated with a shorter time to endpoints and faster tumor growth.ConclusionsCryo combined with the immunostimulant CpG promoted cytotoxic T-cell infiltration into tumors, slowed tumor growth, and prolonged the time to progression to endpoints in an aggressive murine HCC model.

Hepatocellular carcinoma (HCC) is the most common primary liver malignancy, and represents a significant global health burden with rising incidence rates, despite a more thorough understanding of the etiology and biology of HCC, as well as advancements in diagnosis and treatment modalities. According to emerging evidence, imaging features related to tumor aggressiveness can offer relevant prognostic information, hence validation of imaging prognostic features may allow for better noninvasive outcomes prediction and inform the selection of tailored therapies, ultimately improving survival outcomes for patients with HCC.

Abstract Background To develop and validate a nomogram model based on Gd-EOB-DTPA enhanced MRI for differentiation between hepatocellular carcinoma (HCC) and focal nodular hyperplasia (FNH) showing iso- or hyperintensity in the hepatobiliary phase (HBP). Methods A total of 75 patients with 49 HCCs and 26 FNHs randomly divided into a training cohort (n = 52: 34 HCC; 18 FNH) and an internal validation cohort (n = 23: 15 HCC; 8 FNH). A total of 37 patients (n = 37: 25 HCC; 12 FNH) acted as an external test cohort. The clinical and imaging characteristics between HCC and FNH groups in the training cohort were compared. The statistically significant parameters were included into the FAE software, and a multivariate logistic regression classifier was used to identify independent predictors and establish a nomogram model. Receiver operating characteristic (ROC) curves were used to evaluate the prediction ability of the model, while the calibration and decision curves were used for model validation. Subanalysis was used to compare qualitative and quantitative characteristics of patients with chronic hepatitis and cirrhosis between the HCC and FNH groups. Results In the training cohort, gender, age, enhancement rate in the arterial phase (AP), focal defects in uptake were significant predictors for HCC showing iso- or hyperintensity in the HBP. In the training cohort, area under the curve (AUC), sensitivity and specificity of the nomogram model were 0.989(95%CI: 0.967-1.000), 97.1% and 94.4%. In the internal validation cohort, the above three indicators were 0.917(95%CI: 0.782-1.000), 93.3% and 87.5%. In the external test cohort, the above three indicators were 0.960(95%CI: 0.905-1.000), 84.0% and 100.0%. The results of subanalysis showed that age was the independent predictor in the patients with chronic hepatitis and cirrhosis between HCC and FNH groups. Conclusions Gd-EOB-DTPA enhanced MRI nomogram model may be useful for discriminating HCC and FNH showing iso- or hyperintensity in the HBP before surgery.

Background: Hepatocellular carcinoma (HCC) complicated by portal vein thrombosis presents significant clinical challenges. This study aims to retrospectively assess the feasibility of stereotactic irradiation for treating bulky HCC, with or without vascular invasion. Method: In this retrospective analysis, the radiotherapy treatment plans and clinical follow-up data of 22 patients diagnosed with HCC, with or without portal vein thrombosis, were reviewed. These patients underwent stereotactic body radiation therapy (SBRT) between September 2019 and September 2022. Treatment involved administering 40-50 Gy in 5 fractions using SBRT with volumetric modulated arc therapy (VMAT)/4D-computed tomography. Descriptive statistics were utilized without the application of statistical tests. Results: The mean age of the patients was 65 years, with 77% being male. Portal vein thrombosis was present in 73% of the cases, and the average tumor size was 7.2 cm (range 5-12 cm). 59% of patients were classified as Child-Pugh B. The median follow-up duration was 8 months (range 3-36 months). At 3 months, tumor response assessments revealed that 59% of patients had a partial response and 41% had stable disease; by 6 months, 37% achieved complete response, 26% maintained a partial response, and 37% had stable condition. Failure patterns included intrahepatic failure in two patients (at 7 and 9 months) and extrahepatic loss in two others (at 6 and 10 months). Radiation-induced liver disease occurred in two patients at 9- and 11-weeks post-treatment, respectively. Liver cancer-specific mortality was 13.6%, while non-liver cancer-specific mortality stood at 9%. The progression-free survival rate was 82%. Conclusion: SBRT via VMAT represents a highly cost-effective, non-invasive local therapy with a favorable therapeutic ratio for treating bulky HCC cases, with or without vascular invasion.

Introduction: Patients with advanced hepatocellular carcinoma (HCC) have limited treatment options in the context of decompensated cirrhosis. HCC occurs in patients with hepatitis C virus (HCV) infection and cirrhosis at 1–4% per year. Direct-acting antiviral (DAA) efficacy is decreased in the presence of HCC. We present a case where immunotherapy may have resulted in HCV clearance, when DAA therapy had been ineffective. We hypothesise that immune checkpoint inhibitors targeting the PD-1/PD-L1 pathway can reverse T-cell exhaustion and aid in the clearance of chronic HCV. Case Presentation: This case study describes a male in his 40 s identified by a re-engagement initiative for HCV, who had been unaware of his diagnosis. On further investigation he was found to have compensated for liver cirrhosis and HCC. He was treated with HCV DAA therapy (sofosbuvir/velpatasvir) and then systemic immunotherapy for HCC with atezolizumab and bevacizumab, in an attempt to downstage the disease. Hepatitis C therapy did not achieve sustained virological response, with viral relapse after the end of treatment. This, combined with ongoing alcohol use, resulted in hepatic decompensation and cessation of immunotherapy after the fifth cycle. The HCV RNA subsequently became undetectable without further DAA re-treatment. Conclusion: To our knowledge, this is the first case of HCV clearance after DAA relapse and the timing of this event after immunotherapy suggests a causal link. We hypothesise that this may be due to the reversal of antiviral T-cell exhaustion. This would therefore support further investigation into other chronic viral infections that create tumour associated with immunosuppressive microenvironments.

Background: To develop and validate a nomogram model based on Gd-EOB-DTPA enhanced MRI for differentiation between hepatocellular carcinoma (HCC) and focal nodular hyperplasia (FNH) showing iso- or hyperintensity in the hepatobiliary phase (HBP). Methods: A total of 75 patients with 49 HCCs and 26 FNHs randomly divided into a training cohort (n = 52: 34 HCC; 18 FNH) and an internal validation cohort (n = 23: 15 HCC; 8 FNH). A total of 37 patients (n = 37: 25 HCC; 12 FNH) acted as an external test cohort. The clinical and imaging characteristics between HCC and FNH groups in the training cohort were compared. The statistically significant parameters were included into the FAE software, and a multivariate logistic regression classifier was used to identify independent predictors and establish a nomogram model. Receiver operating characteristic (ROC) curves were used to evaluate the prediction ability of the model, while the calibration and decision curves were used for model validation. Subanalysis was used to compare qualitative and quantitative characteristics of patients with chronic hepatitis and cirrhosis between the HCC and FNH groups. Results: In the training cohort, gender, age, enhancement rate in the arterial phase (AP), focal defects in uptake were significant predictors for HCC showing iso- or hyperintensity in the HBP. In the training cohort, area under the curve (AUC), sensitivity and specificity of the nomogram model were 0.989(95%CI: 0.967-1.000), 97.1% and 94.4%. In the internal validation cohort, the above three indicators were 0.917(95%CI: 0.782-1.000), 93.3% and 87.5%. In the external test cohort, the above three indicators were 0.960(95%CI: 0.905-1.000), 84.0% and 100.0%. The results of subanalysis showed that age was the independent predictor in the patients with chronic hepatitis and cirrhosis between HCC and FNH groups. Conclusions: Gd-EOB-DTPA enhanced MRI nomogram model may be useful for discriminating HCC and FNH showing iso- or hyperintensity in the HBP before surgery. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) in the caudate lobe presents surgical challenges due to the lack of distinct anatomical landmarks. This case report introduces a novel surgical approach combining Takasaki's classification and indocyanine green negative counterstaining for precise anatomical caudate lobectomy. A 78-year-old patient with hepatocellular carcinoma in the caudate lobe underwent surgery following preoperative volumetric assessment. The method involved a glissonian approach for both left and right pedicles, coupled with meticulous dissection of hepatic pedicles of the caudate lobe guided by taping of left and right glissonian pedicles, followed by indocyanine green administration for improved visualization of caudate lobe boundaries. The procedure enabled complete tumor resection with minimal blood loss. At 50 months postsurgery, the patient maintains favorable liver function and performance status. This innovative approach offers a promising solution for precise resection of caudate lobe hepatocellular carcinoma, potentially improving surgical outcomes and long-term prognosis. [ABSTRACT FROM AUTHOR]

Objective To investigate the efficacy and safety of tyrosine kinase inhibitor (TKI)combined with immune checkpoint inhibitor as the second-line therapy for advanced hepatocellular carcinoma (HCC). Methods A retrospective analysis was performed for the clinical data of 63 patients with advanced HCC who were admitted to Department of Interventional Radiology, The First Affiliated Hospital of Soochow University, from January 2018 to December 2022, and all patients experienced progression/intolerance after transcatheter arterial chemoembolization combined with first-line TKI and were switched to secondline TKI with or without immune checkpoint inhibitor. The 32 patients receiving second-line TKI with immune checkpoint inhibitor were enrolled as combination group, and the 31 patients receiving second-line TKI alone were enrolled as single treatment group. Modified Response Evaluation Criteria in Solid Tumors was used to evaluate tumor response, and Common Terminology Criteria for Adverse Events 5.0 was used to evaluate adverse events. The Kaplan-Meier method was used to calculate median overall survival (mOS)and median progression-free survival (mPFS)for the two groups, and the two groups were compared in terms of objective response rate (ORR)and disease control rate (DCR). The chi-square test was used for comparison of baseline data and follow-up results between groups. Results The median follow-up time was 16.5(3.2 — 53.4)months for the 63 patients. The combination group had an mOS of 24.3(95% confidence interval ［CI］：20.0—28.6)months and an mPFS of 9.8(95%CI：7.5—12.1)months, while the single treatment group had an mOS of 15.8(95%CI：11.4—20.1)months and an mPFS of 4.1(95%CI：3.2—4.9)months, and there were significant differences in mOS and mPFS between the two groups (P=0.029 and 0.038). The combination group had an ORR of 47% and a DCR of 84%, while the single treatment group had an ORR of 19% and a DCR of 65%； there was a significant difference in ORR between the two groups (P=0.021), but with no significant difference in DCR between the two groups (P= 0.070). As for adverse events, 4 patients (12.5%)in the combination group and 3(10.0%)in the single treatment group experienced grade Ⅲ — Ⅳ serious adverse events, with no fatal drug reactions in either group, and there was no significant difference in the incidence rate of adverse events between the two groups (P=0.783). Conclusion Compared with TKI alone, TKI combined with immune checkpoint inhibitor has a more significant therapeutic effect as the second-line therapy for advanced HCC, without increasing serious adverse reactions [ABSTRACT FROM AUTHOR]

Background Validating the expanded criteria for living donor liver transplantation for hepatocellular carcinoma using national data is highly significant. The aim of this study was to evaluate the validity of the new Japanese criteria for living donor liver transplantation for hepatocellular carcinoma patients and identify factors associated with a poor prognosis using the Japanese national data set. Methods The study population comprised patients who underwent living donor liver transplantation for hepatocellular carcinoma at 37 centres in Japan between 2010 and 2018. In a nationwide survey, the overall survival and recurrence-free survival rates were evaluated based on the new Japanese criteria for applying the 5-5-500 rule when extending the indication beyond the Milan criteria. Prognostic factors within the Japanese criteria were determined using the Cox proportional hazards model. Results Patients within (485 patients) and beyond (31 patients) the Japanese criteria exhibited 5-year overall survival rates of 81% and 58% and 5-year recurrence-free survival rates of 77% and 48% respectively. Patients who met the Milan criteria, but not the 5-5-500 rule, had poorer outcomes. Multivariate analysis for 474 patients identified a neutrophil-to-lymphocyte ratio greater than or equal to 5 and a history of hepatectomy as independent risk factors. Conclusion This nationwide survey confirms the validity of the Japanese criteria. The poor prognostic factors within the Japanese criteria include a neutrophil-to-lymphocyte ratio greater than or equal to 5 and previous hepatectomy. [ABSTRACT FROM AUTHOR]

Introduction: It is not known if the nature, number and duration of presenting symptoms at diagnosis of hepatocellular carcinoma impact on overall survival. This study examines whether the presenting symptoms of hepatocellular carcinoma have a significant impact on prognosis. Methods: The study cohort comprised 725 patients with symptomatic hepatocellular carcinoma seen in our department since October 1983. Another 545 patients were diagnosed on surveillance or from incidental findings. Presenting symptoms at diagnosis were documented. A survival census was performed on 31 October 2015 with the national registry of deaths. Presenting symptoms were examined for association with overall survival using multivariable Cox regression analysis. Survival analysis was done by Kaplan-Meier method with log-rank testing. Bivariate Pearson correlation was used to look for any association between duration of symptoms and overall survival. Results: Patients with symptomatic hepatocellular carcinoma had a significantly shorter survival than those diagnosed incidentally or on screening (94.0 vs. 786.0 days, P < 0.001). Survival was shorter in patients presenting with fluid retention (56.0 vs. 118.0 days, P < 0.001), jaundice (48.0 vs. 94.0 days, P = 0.017) and two or more symptoms (P = 0.010). Pain was associated with better survival (P < 0.001). On multivariable Cox regression analysis, only fluid retention (hazard ratio [HR] 1.56, 95% confidence interval [CI] 1.30-1.87) and jaundice (HR 1.36, 95% CI 1.07-1.74) were independently associated with shorter survival. There was no significant relationship between the duration of symptoms and overall survival. Conclusion: Patients with hepatocellular carcinoma who present with fluid retention or jaundice have significantly shorter overall survival. This is useful in assessing patients at the time of diagnosis. [ABSTRACT FROM AUTHOR]

Background: Hepatocellular carcinoma (HCC) complicated by portal vein thrombosis presents significant clinical challenges. This study aims to retrospectively assess the feasibility of stereotactic irradiation for treating bulky HCC, with or without vascular invasion. Method: In this retrospective analysis, the radiotherapy treatment plans and clinical follow-up data of 22 patients diagnosed with HCC, with or without portal vein thrombosis, were reviewed. These patients underwent stereotactic body radiation therapy (SBRT) between September 2019 and September 2022. Treatment involved administering 40-50 Gy in 5 fractions using SBRT with volumetric modulated arc therapy (VMAT)/4D-computed tomography. Descriptive statistics were utilized without the application of statistical tests. Results: The mean age of the patients was 65 years, with 77% being male. Portal vein thrombosis was present in 73% of the cases, and the average tumor size was 7.2 cm (range 5-12 cm). 59% of patients were classified as Child-Pugh B. The median follow-up duration was 8 months (range 3-36 months). At 3 months, tumor response assessments revealed that 59% of patients had a partial response and 41% had stable disease; by 6 months, 37% achieved complete response, 26% maintained a partial response, and 37% had stable condition. Failure patterns included intrahepatic failure in two patients (at 7 and 9 months) and extrahepatic loss in two others (at 6 and 10 months). Radiation-induced liver disease occurred in two patients at 9- and 11-weeks post-treatment, respectively. Liver cancer-specific mortality was 13.6%, while non-liver cancer-specific mortality stood at 9%. The progression-free survival rate was 82%. Conclusion: SBRT via VMAT represents a highly cost-effective, non-invasive local therapy with a favorable therapeutic ratio for treating bulky HCC cases, with or without vascular invasion. [ABSTRACT FROM AUTHOR]

Background: MASLD can manifest as hepatocellular damage, which can result in mild elevation of aminotransferases. However, in some patients, MASLD presents with cholestatic pattern. Objective: To assess the impact of the biochemical pattern on the natural course of MASLD, including liver damage in histology, the accuracy of non-invasive tests(NITs), and prognosis. Methods: Multicenter study enrolling 2156 patients with biopsy-proven MASLD, who were classified based on their[ALT/ULN)]/[(ALP/ULN)] levels at the time of biopsy: (a) hepatocellular pattern(H), > 5; (b) mixed pattern(M),2–5; (c) cholestatic pattern(C), < 2. Outcomes: (a) histological evaluation of the single components of NAS, MASH, and fibrosis; (b) NITs and transient elastography assessing advanced fibrosis; (c) prognosis determined by the appearance of decompensated cirrhosis and death. Results: Out of the 2156 patients, 22.9% exhibited the H-pattern, whilst 31.7% exhibited the C-pattern. Severe steatosis, ballooning, lobular inflammation, and MASH (56.4% H vs. 41.9% M vs. 31.9% C) were more common in H-pattern (p = 0.0001),whilst C-pattern was linked to cirrhosis (5.8% H vs. 5.6% M vs. 10.9% C; p = 0.0001). FIB-4(0.74(95% CI 0.69–0.79) vs. 0.83 (95% CI 0.80–0.85); p = 0.005) and Hepamet Fibrosis Score(0.77 (95% CI 0.69–0.85) vs. 0.84 (95% CI 0.80–0.87); p = 0.044)exhibited lower AUROCs in the H-pattern. The C-pattern[HR 2.37 (95% CI 1.12–5.02); p = 0.024], along with age, diabetes, and cirrhosis were independently associated with mortality. Most patients maintained their initial biochemical pattern during the second evaluation. Conclusions: The H-pattern exhibited greater necro-inflammation in the histology than the C-pattern, whereas the latter showed more cirrhosis. The accuracy of NITs in detecting fibrosis was decreased in H-pattern. The occurrence of decompensated events and mortality was predominant in C-pattern. Therefore, identifying MASLD phenotypes based on the biochemical presentation could be relevant for clinical practice. [ABSTRACT FROM AUTHOR]

Angiogenesis is a key process in the development and progression of hepatocellular carcinoma （HCC） and can provide essential material conditions for the proliferation, invasion, and metastasis of HCC cells. Inhibition of angiogenesis has become a research hotspot in the field of HCC therapy. Traditional Chinese medicine has become a potential drug for HCC therapy due to its characteristics of multiple targets and pathways, enhancing efficacy and reducing toxicity, improving tumor prognosis, and prolonging survival time. Modern studies have confirmed that traditional Chinese medicine can inhibit tumor angiogenesis by inhibiting the expression of angiogenic factors, upregulating the levels of anti-angiogenic factors, inhibiting endothelial cell proliferation, reducing the microvascular density of HCC tissue, and regulating related signaling pathways, and therefore, traditional Chinese medicine has unique advantages in the treatment of HCC. By summarizing related articles in China and globally in recent years, this article analyzes the mechanism of action of traditional Chinese medicine on inhibiting HCC angiogenesis, in order to provide certain theoretical basis and reference for the optimization of HCC treatment strategies in clinical practice. [ABSTRACT FROM AUTHOR]

Objective. To systematically evaluate the efficacy and safety of three-dimensional visualization technology in assisting ablation therapy for hepatocellular carcinoma. Methods This study was conducted according to PRISMA guidelines, with a PROSPERO registration number of CRD42023488398. PubMed, Embase, Web of Science, the Cochrane Library, CNKI. Wandang Data, VIP, and CBM weze searched for Chinese and English articles on three-dimensional visualization technology in assisting ablation therapy for hepatocellular carcinoma published up to Manh 2023. After quality assessment and data extraction of the studies included, RevMan 5.4 software was used to perform the meta-analyses. Results A total of 11 studies were included. with 972 patients in total, among whom 447 underwent ablation assisted by three-dimensional visualization technology (30 group) and 525 underwent ablation assisted by traditional two-dimensional imaging technology (20 goup). The meta-analysis showed that compared with the 210 group, the 30 group had significantly higher success rate of fust-time ablation treatment (odds ratio [OR]= 5.43, 95% confidence interval (CI): 2.64-11.18, P<0.001), technical efficiency (OR=6.15, 95%CI: 3.23-11.70, P<0.001), and complete ablation rate (OR-2.50, 95%(7: 1.08-5.78. P = 0.03 ). as well as significantly lower incidence rate of major complications (OR=0.45, 95% CI, 0.24-0.87, P-002), local recurrence rate (OR=0.35, 95%CI: 0.17-0.72, P = 0.004 ). and local tumor progression rate (0R = 0.29), 95%C7; 0.16-0.50, /<0.001), while there was no significant difference in the incidence rate of mild complications between the two groups (P > 0.05) Conclusion Three-dimensional visualization technology is safe and feasible in assisting ablation therapy for hepatocellular carcinoma and can improve ablation rate and reduce the incidence tate of serious complications. local recurrence rate, and local tumor progression rate, thereby showing an important application value in clinical practice. [ABSTRACT FROM AUTHOR]

To investigate the value of serum cell cycle protein-dependent kinase 1 (CDKI) and aurora kinase A (AURKA) in the diagnosis of patients with hepatitis B virus-related hepatocellular carcinoma (HBV-HCC). Methods A total of 50 HBV-HCC patients, 50 patients with hepatitis B virus-related liver cirrhosis (HBV-LC), and 50 chronic hepatitis B (CHB) patients who were hospitalized in Department of Gastroenterology, Gansu Provincial Hospital, fmm June 2022 to December 2023 were enrolled, and 50 healthy individuals, matched for age and sex, who received physical examination at Physical Examination Center during the same period of time were enrolled as control group. Related data were reconded for all patients, including age, sex, complications, and the results of routine blood test, liver function, and onagulation for the first time after admission. ELISA was used to measure the serum levels of CDK1 and AURKA. A one-way analysis of variance was used for comparison of normally distributed continuous data between multiple groups, and the least significant difference t-test was used for further comparison between two groups; the Kruskal-Wallis H test was used for comparison of non-normally distributed continuous data between multiple groups and the least significant difference Bonferroni test was used for further comparison between two groups, the chi- square test or the Fisher's exact test was used for comparison of categorical data between groups. The Spesaman correlation analysis was used to investigate the correlation between CDKI and AURKA, and the woeier operating characteristic (ROC) curve and the arra under the ROC curve (AUC) were used to investigate the value of CDK1 and AURKA in the diamosis of HBV-HCC. Results There were significant differences in liver function garameters between the HBV-HCC patients and the control group (all P<0.05); there were significant differences between the CHB group and the HBV-HCC group in albumin, Glh, dirret hilirubin, aspartate aminotransferase (AST), gamma-glutamyl transpeptidase (GGT) and alkaline phosphatase (all P<0.05); there were significant differences between the HIIV-LC group and the HBV-HCC group in Glb, AST, aml GGT (all P<0.05). The HBV- HCC group had significantly higher serum levels of CDKI and AURKA than the HBV-LC group, the CHB group, and the control group (all P<0.05). There was a significant positive correlation between CDKI and AURKA in the overall study population and the HBV-HCC patients (r=0.526 6 and 0.815 2. P<0.001), With the control group as reference, CDKI had an AUC of 0.832 3 in the diagnosis of HBV-HCC, with a sensitivity of 92.86% and a specificity of 75%, and AURKA had an ALC of 0.886 6 in the diagnosis of HCC. with a sensitivity of 95.80% and a specificity of 74%. With the CHB group as reference, CDKI had an AUC of 0.833 3 in the diagnosis of HBV-HCC, with a sensitivity of 93.75% and a specificity of 75%, and AURKA had an AUC of 0.972 7 in the diagnosis of HBV-HCC, with a sensitivity of 95.83% aml a specificity of 91.67%. With the HBV-LC group as reference. CDKI had an AUC of 0.608 5 in the diagnosis of HBV-HCC, with a sensitivity of 66.67% and a specificity of 54.17%, and AURKA had an AUC of 0.762 2 in the diagnosis of HBV-HCC, with a sensitivity of 95.83% and a specificity of 47.92%. Conclusion The serum levels of CDK1 and AURKA increase with the progression of hepatitis B-associated chronic liver disease, and significant increases in serum CDKI and AURKA have a certain value in the diagnosis of HBV HOC. [ABSTRACT FROM AUTHOR]

In June 2017, National Health Commission of the People's Republic of China released Guidelines for the diagnosis and treatment of primary liver cancer (2017 edition), which provided important recommendations for the diagnosis, staging, and treatment of liver cancer. Since then, high-level evidence in line with the principles of evidence-based medicine has been continuously obtained from the research on primary liver cancer in China and globally. Therefore, National Health Commission released Guidelines for the diagnosis and treatment of primary liver cancer (2024 edition). This article gives an interpretation of the updated key points in the guidelines, in order to better guide clinical practice. [ABSTRACT FROM AUTHOR]

Objective To investigate the effect of preoperative anxiety on postoperative recovery and short-term prognosis in patients with liver cancer resection. Methods A total of 96 patients underwent elective open hepatocellular carcinoma resection, with American Society of Anesthesiologists (ASA) grade Ⅰ-Ⅱ were included in this study. Patients were divided into the control group (41 cases, HAMA < 7 points) and the anxiety group (55 cases, HAMA ≥7 points) according to Hamilton Anxiety Scale (HAMA). Heart rate (HR), mean arterial pressure (MAP) after entering the operating room, operative time, intraoperative bleeding, intraoperative fluid infusion and intraoperative remifentanil consumption were monitored in patients. Recovery time, extubation time, Emergence Agitation (EA) score, the resting and dynamic visual analogue scale ( VAS ) at 5 min after extubation (T1), 6 h (T2), 12 h (T3), 24h (T4) and 48 h (T5) after surgery, the cumulative effective pressing times of patient controlled analgesia (PCA), the remedy times of analgesic drugs, the postoperative gastrointestinal reaction, exhaust time, hospital stay, the serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels at the 5th day after operation were recorded. Results Compared with the control group, the heart rate and MAP in the anxious group were significantly increased after entering operating room, and the recovery time and extubation time were significantly prolonged (P＜0.05). The incidence of intraoperative remifentanil consumption, EA score, T1, T2, T3 resting and dynamic VAS score, T4 dynamic VAS score, PCA pressing times, analgesic drug remedy times and postoperative gastrointestinal reactions were significantly higher in the anxious group than those in the control group (P＜ 0.05), and incidence of gastrointestinal reactions, postoperative out of bed time, exhaust time, feeding time and hospital stay were significantly prolonged (P＜0.05). Conclusion Preoperative anxiety is not conducive to anesthesia recovery and shortterm prognosis in patients with liver tumor resection. [ABSTRACT FROM AUTHOR]

Purpose: Nivolumab and regorafenib are second-line therapies for patients with advanced hepatocellular carcinoma (HCC). We aimed to compare the effectiveness of nivolumab and regorafenib. Materials and Methods: We retrospectively reviewed patients with HCC treated with nivolumab or regorafenib after sorafenib failure. Progression-free survival (PFS) and overall survival (OS) were analyzed. An inverse probability of treatment weighting using the propensity score (PS) was performed to reduce treatment selection bias. Results: Among the 189 patients recruited, 137 and 52 patients received regorafenib and nivolumab after sorafenib failure, respectively. Nivolumab users showed higher Child-Pugh B patients (42.3% vs. 24.1%) and shorter median sorafenib maintenance (2.2 months vs. 3.5 months) compared to regorafenib users. Nivolumab users showed shorter median OS (4.2 months vs. 7.4 months, p=0.045) than regorafenib users and similar median PFS (1.8 months vs. 2.7 months, p=0.070). However, the median overall and PFS did not differ between the two treatment groups after the 1:1 PS matching (log-rank p=0.810 and 0.810, respectively) and after the stabilized inverse probability of treatment weighting (log-rank p=0.445 and 0.878, respectively). In addition, covariate-adjusted Cox regression analyses showed that overall and PFS did not significantly differ between nivolumab and regorafenib users after 1:1 PS matching and stabilized inverse probability of treatment weighting (all p>0.05). Conclusion: Clinical outcomes of patients treated with nivolumab and regorafenib after sorafenib treatment failure did not differ significantly. [ABSTRACT FROM AUTHOR]

Introduction: Patients with advanced hepatocellular carcinoma (HCC) have limited treatment options in the context of decompensated cirrhosis. HCC occurs in patients with hepatitis C virus (HCV) infection and cirrhosis at 1–4% per year. Direct-acting antiviral (DAA) efficacy is decreased in the presence of HCC. We present a case where immunotherapy may have resulted in HCV clearance, when DAA therapy had been ineffective. We hypothesise that immune checkpoint inhibitors targeting the PD-1/PD-L1 pathway can reverse T-cell exhaustion and aid in the clearance of chronic HCV. Case Presentation: This case study describes a male in his 40 s identified by a re-engagement initiative for HCV, who had been unaware of his diagnosis. On further investigation he was found to have compensated for liver cirrhosis and HCC. He was treated with HCV DAA therapy (sofosbuvir/velpatasvir) and then systemic immunotherapy for HCC with atezolizumab and bevacizumab, in an attempt to downstage the disease. Hepatitis C therapy did not achieve sustained virological response, with viral relapse after the end of treatment. This, combined with ongoing alcohol use, resulted in hepatic decompensation and cessation of immunotherapy after the fifth cycle. The HCV RNA subsequently became undetectable without further DAA re-treatment. Conclusion: To our knowledge, this is the first case of HCV clearance after DAA relapse and the timing of this event after immunotherapy suggests a causal link. We hypothesise that this may be due to the reversal of antiviral T-cell exhaustion. This would therefore support further investigation into other chronic viral infections that create tumour associated with immunosuppressive microenvironments. [ABSTRACT FROM AUTHOR]

Magnetic resonance elastography (MRE) is a noninvasive tool for diagnosing hepatic fibrosis with high accuracy. We investigated the preoperative clinical and imaging predictors of intrahepatic recurrence after curative resection of hepatocellular carcinoma (HCC), and evaluated MRE as a predictor of intrahepatic recurrence. We retrospectively evaluated 80 patients who underwent preoperative contrast-enhanced magnetic resonance imaging (MRI) with two-dimensional MRE and curative resection for treatment-naïve HCC between May 2019 and December 2021. Liver stiffness (LS) was measured on the elastograms, and the optimal cutoff of LS for predicting intrahepatic recurrence was obtained using receiver operating characteristic (ROC) analysis. An LS above this cutoff was defined as MRE-recurrence. Preoperative imaging features of the tumor were assessed on MRI, including features in the Liver Imaging Reporting and Data System and microvascular invasion (MVI). Recurrence-free survival (RFS) rates were estimated using the Kaplan-Meier method, and differences were compared using the log-rank test. Using a Cox proportional hazards model, we conducted a multivariable analysis to investigate the factors affecting recurrence-free survival. During a median follow-up period of 32 months (range, 4–52 months), thirteen patients (16.3%) developed intrahepatic recurrence. ROC analysis determined an LS cutoff of ≥4.35 kPa to define MRE-recurrence. The 4-year RFS rate was significantly higher in patients without MRE-recurrence than in those with MRE-recurrence (93.4% vs. 48.9%; p = 0.001). In multivariable analysis, MRE-recurrence (Hazard ratio [HR], 5.9; 95% confidence interval [CI], 1.5–23.1) and MVI (HR, 3.4; 95% CI, 1.0–11.3) were independent predictors of intrahepatic recurrence. Patients without MRE-recurrence had significantly higher RFS rates than those with MRE-recurrence. MRE-recurrence and MVI were independent predictors of intrahepatic recurrence in patients after curative resection for HCC. • In at-risk patients after HCC resection, liver stiffness ≥4.35 kPa from pre-op MRE could predict intrahepatic recurrence. • Preoperative MRE may predict late recurrence >2 years after surgery and is associated with the occurrence of de novo HCC. • Preoperative MRE could help establish individualized treatment strategies and plans for recurrence surveillance. [ABSTRACT FROM AUTHOR]

Sarcomatoid hepatocellular carcinoma is a rare histologic variant of primary liver cancer comprising of malignant spindle cells and typical hepatocellular carcinoma (HCC). In terms of clinical presentation, they usually exhibit extensive tumor burden due to their larger size and a metastatic disease at the time of diagnosis as compared to conventional HCC. Tumor lysis syndrome is an oncological emergency, usually seen after cytotoxic chemotherapy in haematological malignancies. Here, we highlight a case of 76-year old male with no comorbidities, presenting with an excruciating backache and a paravertebral soft tissue mass and multiple osteolytic lesions, was clinically suspected to be a plasma cell neoplasm. On further evaluation, the patient was diagnosed of a sarcomatoid variant of hepatocellular carcinoma. This report showcases multiple rare findings by the presence of non-specific symptoms, non-cirrhotic liver, normal serum alpha protein levels and the occurrence of a spontaneous tumor lysis syndrome in a solid malignancy. [ABSTRACT FROM AUTHOR]

Purpose: To compare the efficacy of transarterial chemoembolization (TACE) combined with tyrosine kinase inhibitors (TKIs) plus immune checkpoint inhibitors (ICIs) (TACE-TKI-ICI) versus TKIs plus ICIs (TKI-ICI) for unresectable hepatocellular carcinoma (HCC) with first- or lower-order portal vein tumor thrombosis (PVTT). Materials and Methods: A retrospective study was performed in HCC patients with first- or lower-order PVTT receiving TKIs (Lenvatinib or sorafenib) plus ICIs (camrelizumab, sintilimab, or atezolizumab) with or without TACE from four institutions between January 2019 and January 2022. Propensity score–based method was performed to minimize bias by confounding factors. Tumor response, progression-free survival (PFS), overall survival (OS), and adverse events (AEs) were evaluated and compared between the two groups. Results: After inverse probability of treatment weighting, two balanced pseudopopulations were created: 106 patients in the TACE-TKI-ICI group and 109 patients in the TKI-ICI group. The objective response rate was higher in the TACE-TKI-ICI group (50.9% vs. 28.4%, P < 0.001). The median PFS and OS were significantly longer in the TACE-TKI-ICI group than in the TKI-ICI group (PFS: 9.1 vs. 5.0 months, P = 0.005; OS: 19.1 vs. 12.7 months, P = 0.002). In Cox regression, TACE-TKI-ICI treatment was an independent predictor of favorable OS. Treatment-related grade 3/4 AEs were comparable between the two groups (22.6% vs. 17.9%, P = 0.437). Conclusion: TACE-TKI-ICI therapy contributed to better tumor control, PFS and OS than TKI-ICI therapy in unresectable HCC patients with first- or lower-order PVTT. [ABSTRACT FROM AUTHOR]