The causal effect of gut microbiota on hepatic encephalopathy: a mendelian randomization analysis.

BACKGROUND: There is growing evidence for a relationship between gut microbiota and hepatic encephalopathy (HE). However, the causal nature of the relationship between gut microbiota and HE has not been thoroughly investigated. METHOD: This study utilized the large-scale genome-wide association studies (GWAS) summary statistics to evaluate the causal association between gut microbiota and HE risk. Specifically, two-sample Mendelian randomization (MR) approach was used to identify the causal microbial taxa for HE. The inverse variance weighted (IVW) method was used as the primary MR analysis. Sensitive analyses were performed to validate the robustness of the results. RESULTS: The IVW method revealed that the genus Bifidobacterium (OR = 0.363, 95% CI: 0.139-0.943, P = 0.037), the family Bifidobacteriaceae (OR = 0.359, 95% CI: 0.133-0.950, P = 0.039), and the order Bifidobacteriales (OR = 0.359, 95% CI: 0.133-0.950, P = 0.039) were negatively associated with HE. However, no causal relationship was observed among them after the Bonferroni correction test. Neither heterogeneity nor horizontal pleiotropy was found in the sensitivity analysis. CONCLUSION: Our MR study demonstrated a potential causal association between Bifidobacterium, Bifidobacteriaceae, and Bifidobacteriales and HE. This finding may provide new therapeutic targets for patients at risk of HE in the future.

Clinical effectiveness of DEM-TACE combined with first-line chemotherapy as the initial treatment for patients with unresectable intrahepatic cholangiocarcinoma.

PURPOSE: This study aimed to evaluate the safety and effectiveness of the combination of DEM-TACE with chemotherapy in treating unresectable intrahepatic cholangiocarcinoma (ICC). MATERIALS AND METHODS: 70 patients diagnosed with unresectable ICC between Jan. 2016 and Dec. 2020 were retrospectively included in this study. Of these, 39 patients received DEM-TACE and first-line chemotherapy (D-TACE+Chemo group) and 31 received chemotherapy alone (Chemo group). Propensity score matching (PSM) was performed to reduce selection bias between the D-TACE+Chemo and the Chemo groups. Differences in tumor response, progression-free survival (PFS), overall survival (OS), and treatment-related adverse events (TRAEs) were compared between the two groups . RESULTS: The patients in the D-TACE+Chemo group had better median OS (18.6 vs. 11.9 months, P=0.018), median PFS (11.9 vs. 6.9 months, P=0.033), and objective response rates (56.8% vs. 13.3%, P < 0.001) than those in the Chemo group. TRAEs showed that a higher incidence of transient elevation of transaminase and abdominal pain in the D-TACE+Chemo group than in the Chemo group (P < 0.001). CONCLUSIONS: Compared with chemotherapy alone, DEM-TACE combined with first-line chemotherapy may be a viable and safe treatment option for unresectable ICC.

Role of inflammatory biomarkers in mediating the effect of lipids on spontaneous intracerebral hemorrhage: a two-step, two-sample Mendelian randomization study.

Background: Spontaneous intracerebral hemorrhage (sICH) is a form of stroke with high mortality rates and significant neurological implications for patients. Abnormalities in lipid metabolism have been implicated in various cardiovascular diseases, yet their relationship with sICH remains insufficiently explored, particularly concerning their association with inflammatory factors. Methods: Employing a two-sample, two-step Mendelian Randomization approach, combined with data from GWAS datasets, to investigate the causal relationship between plasma lipid levels and sICH. Additionally, the role of inflammatory factors in this relationship was examined, and sensitivity analyses were conducted to ensure the robustness of the results. Results: The results indicate a significant causal relationship between 19 plasma lipid metabolites and sICH. Furthermore, mediation analysis revealed that three distinct lipids, namely Sterol ester (27:1/20:2), Phosphatidylcholine (16:0_20:4), and Sphingomyelin (d34:1), exert their influence on sICH through inflammatory factors. TRAIL (OR: 1.078, 95% CI: 1.016-1.144, p = 0.013) and HGF (OR: 1.131, 95% CI: 1.001-1.279, p = 0.049) were identified as significant mediators. Conclusion: This study provides new evidence linking abnormalities in lipid metabolism with sICH and elucidates the role of inflammatory factors as mediators. These findings contribute to a better understanding of the pathogenesis of sICH and offer novel insights and therapeutic strategies for its prevention and treatment.

Hepatic Arterial Infusion Chemotherapy Combined with Lenvatinib and PD-1 Inhibitors for Managing Arterioportal Shunt in Hepatocellular Carcinoma with Portal Vein Tumor Thrombus: A Retrospective Cohort Study.

Purpose: This study aimed to assess the effectiveness and safety of combining hepatic arterial infusion chemotherapy (HAIC) with lenvatinib (LEN) and PD-1 inhibitors in treating arterioportal shunt (APS) in hepatocellular carcinoma (HCC) patients with portal vein tumor thrombus (PVTT). Patients and Methods: Conducted retrospectively, the study enrolled 54 HCC patients with APS and PVTT treated with HAIC, LEN, and PD-1 inhibitors at our center between January 2021 and October 2023. APS improvement, APS recanalization, tumor response, PVTT response rate, overall survival (OS), intrahepatic progression-free survival (InPFS), and adverse events were evaluated. Results: APS improvement was observed in 42 patients (77.8%), with all improvement occurring within two treatment sessions. Complete APS occlusion was achieved in 40 patients (74.1%), and no recanalization occurred. The best objective response rate (ORR) and ORR after two HAIC sessions were 74.1% and 66.7%, respectively. The best PVTT response and PVTT response after two HAIC sessions were 98.1% and 94.4%, respectively. The median OS and InPFS were 10.0 months and 5.0 months, respectively. OS and InPFS were longer in patients with APS occlusion compared to those without (OS 12.1 vs 4.4 months, P<0.001, InPFS 6.2 vs 2.3 months, P=0.049). ALBI grade, extrahepatic spread, APS disappearance were potential prognostic factors for OS, while APS grade and extrahepatic spread being independently associated with InPFS. No treatment-related mortality occurred. Conclusion: Combining HAIC with LEN and PD-1 inhibitors proves to be both effective and safe in managing APS in HCC with PVTT, potentially improving patient survival.

Hepatic-associated vascular morphological assessment to predict overt hepatic encephalopathy before TIPS: a multicenter study.

BACKGROUND: To provide patients the chance of accepting curative transjugular intrahepatic portosystemic shunt (TIPS) rather than palliative treatments for portal hypertension-related variceal bleeding and ascites, we aimed to assess hepatic-associated vascular morphological change to improve the predictive accuracy of overt hepatic encephalopathy (HE) risks. METHODS: In this multicenter study, 621 patients undergoing TIPS were subdivided into training (413 cases from 3 hospitals) and external validation datasets (208 cases from another 3 hospitals). In addition to traditional clinical factors, we assessed hepatic-associated vascular morphological changes using maximum diameter (including absolute and ratio values). Three predictive models (clinical, hepatic-associated vascular, and combined) were constructed using logistic regression. Their discrimination and calibration were compared to test the necessity of hepatic-associated vascular assessment and identify the optimal model. Furthermore, to verify the improved performance of ModelC-V, we compared it with four previous models, both in discrimination and calibration. RESULTS: The combined model outperformed the clinical and hepatic-associated vascular models (training: 0.814, 0.754, 0.727; validation: 0.781, 0.679, 0.776; p < 0.050) and had the best calibration. Compared to previous models, ModelC-V showed superior performance in discrimination. The high-, middle-, and low-risk populations displayed significantly different overt HE incidence (p < 0.001). Despite the limited ability of pre-TIPS ammonia to predict overt HE risks, the combined model displayed a satisfactory ability to predict overt HE risks, both in the low- and high-ammonia subgroups. CONCLUSION: Hepatic-associated vascular assessment improved the predictive accuracy of overt HE, ensuring curative chances by TIPS for suitable patients and providing insights for cirrhosis-related studies.

Immune checkpoint inhibitors and anti-vascular endothelial growth factor antibody/tyrosine kinase inhibitors with or without transarterial chemoembolization as first-line treatment for advanced hepatocellular carcinoma (CHANCE2201): a target trial emulation study.

Background: The role of transarterial chemoembolization (TACE) in the treatment of advanced hepatocellular carcinoma (HCC) is unconfirmed. This study aimed to assess the efficacy and safety of immune checkpoint inhibitors (ICIs) plus anti-vascular endothelial growth factor (anti-VEGF) antibody/tyrosine kinase inhibitors (TKIs) with or without TACE as first-line treatment for advanced HCC. Methods: This nationwide, multicenter, retrospective cohort study included advanced HCC patients receiving either TACE with ICIs plus anti-VEGF antibody/TKIs (TACE-ICI-VEGF) or only ICIs plus anti-VEGF antibody/TKIs (ICI-VEGF) from January 2018 to December 2022. The study design followed the target trial emulation framework with stabilized inverse probability of treatment weighting (sIPTW) to minimize biases. The primary outcome was overall survival (OS). Secondary outcomes included progression-free survival (PFS), objective response rate (ORR), and safety. The study is registered with ClinicalTrials.gov, NCT05332821. Findings: Among 1244 patients included in the analysis, 802 (64.5%) patients received TACE-ICI-VEGF treatment, and 442 (35.5%) patients received ICI-VEGF treatment. The median follow-up time was 21.1 months and 20.6 months, respectively. Post-application of sIPTW, baseline characteristics were well-balanced between the two groups. TACE-ICI-VEGF group exhibited a significantly improved median OS (22.6 months [95% CI: 21.2-23.9] vs 15.9 months [14.9-17.8]; P < 0.0001; adjusted hazard ratio [aHR] 0.63 [95% CI: 0.53-0.75]). Median PFS was also longer in TACE-ICI-VEGF group (9.9 months [9.1-10.6] vs 7.4 months [6.7-8.5]; P < 0.0001; aHR 0.74 [0.65-0.85]) per Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1. A higher ORR was observed in TACE-ICI-VEGF group, by either RECIST v1.1 or modified RECIST (41.2% vs 22.9%, P < 0.0001; 47.3% vs 29.7%, P < 0.0001). Grade ≥3 adverse events occurred in 178 patients (22.2%) in TACE-ICI-VEGF group and 80 patients (18.1%) in ICI-VEGF group. Interpretation: This multicenter study supports the use of TACE combined with ICIs and anti-VEGF antibody/TKIs as first-line treatment for advanced HCC, demonstrating an acceptable safety profile. Funding: National Natural Science Foundation of China, National Key Research and Development Program of China, Jiangsu Provincial Medical Innovation Center, Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, and Nanjing Life Health Science and Technology Project.

Transarterial Chemoembolization (TACE) Combined with Lenvatinib versus TACE Alone in Intermediate-Stage Hepatocellular Carcinoma Patients Beyond Up-To-Seven Criteria: A Retrospective, Propensity Score-Matched Analysis.

RATIONALE AND OBJECTIVES: To compare the treatment efficacy and safety of transarterial chemoembolization (TACE) combined with lenvatinib versus TACE alone in patients with intermediate-stage hepatocellular carcinoma (HCC) beyond up-to-seven criteria. MATERIALS AND METHODS: A total of 107 newly diagnosed HCC patients with Barcelona Clinic Liver Cancer stage B HCC beyond up-to-seven criteria were included in this retrospective cohort study. These patients were divided into two groups: TACE-Lenv group and TACE alone group. Propensity score matching was used to account for potential confounding factors. Overall survival (OS), progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), downstaging rate, liver function, and adverse events (AEs) were recorded and evaluated. RESULTS: Both the median OS and median PFS were significantly longer in the TACE-Lenv group compared to the TACE alone group (median OS: 28.0 vs 12.0 months, P = 0.017; median PFS [mRECIST]: 8.2 vs 3.7 months, P = 0.018; median PFS [RECIST v1.1]: 8.9 vs 3.7 months, P = 0.003). Furthermore, the ORR and DCR were also significantly higher in TACE-Lenv group (ORR: 94% [30/32] vs 47% [15/32], P < 0.001; DCR: 97% [31/32] vs 62% [20/32], P < 0.001). There were no significant differences in terms of liver function and grade 3 or 4 AEs rate between two groups. CONCLUSION: The combination of TACE and lenvatinib provides clinical benefits for patients with intermediate HCC beyond the up-to-seven criteria, has an acceptable safety profile, shows a trend towards improving liver function, and does not increase the occurrence of grade 3-4 AEs. KEY POINTS: The efficacy of transarterial chemoembolization in intermediate-stage hepatocellular carcinoma patients is partially unsatisfactory. Addition of lenvatinib to transarterial chemoembolization improves OS, PFS, ORR, and DCR for patients with intermediate-stage hepatocellular carcinoma beyond the up-to-seven criteria. This combination therapy is a superior treatment option for intermediate-stage hepatocellular carcinoma patients with high tumor burden.

Causal effects of immune cells in glioblastoma: a Bayesian Mendelian Randomization study.

Background: Glioblastoma (GBM) is a highly malignant brain tumor, and immune cells play a crucial role in its initiation and progression. The immune system's cellular components, including various types of lymphocytes, macrophages, and dendritic cells, among others, engage in intricate interactions with GBM. However, the precise nature of these interactions remains to be conclusively determined. Method: In this study, a comprehensive two-sample Mendelian Randomization (MR) analysis was conducted to elucidate the causal relationship between immune cell features and the incidence of GBM. Utilizing publicly available genetic data, we investigated the causal associations between 731 immune cell signatures and the risk of GBM. Subsequently, we conducted a reverse Mendelian randomization analysis to rule out reverse causation. Finally, it was concluded that there is a unidirectional causal relationship between three subtypes of immune cells and GBM. Comprehensive sensitivity analyses were employed to validate the results robustness, heterogeneity, and presence of horizontal pleiotropy. To enhance the accuracy of our results, we concurrently subjected them to Bayesian analysis. Results: After conducting MR analyses, we identified 10 immune phenotypes that counteract glioblastoma, with the most protective being FSC-A on Natural Killer T cells (OR = 0.688, CI = 0.515-0.918, P = 0.011). Additionally, we found 11 immune cell subtypes that promote GBM incidence, including CD62L- HLA DR++ monocyte % monocyte (OR = 1.522, CI = 1.004-2.307, P = 0.048), CD4+CD8+ T cell % leukocyte (OR = 1.387, CI = 1.031-1.866, P = 0.031). Following the implementation of reverse MR analysis, where glioblastoma served as the exposure variable and the outcomes included 21 target immune cell subtypes, we discerned that only three cell subtypes (CD45 on CD33+ HLA DR+ CD14dim, CD33+ HLA DR+ Absolute Count, and IgD+ CD24+ B cell Absolute Count) exhibited a unidirectional causal association with glioblastoma. Conclusion: Our study has genetically demonstrated the close relationship between immune cells and GBM, guiding future clinical research.

Transjugular intrahepatic portosystemic shunt for portal hypertension with chronic portal vein occlusion.

PURPOSE: This study aims to evaluate the long-term patency of transjugular intrahepatic portosystemic shunt (TIPS) and determine the predictors of shunt dysfunction in patients with chronic portal vein occlusion (CPVO). METHOD: This retrospective study was conducted from December 2010 to December 2020 in patients with portal hypertension and CPVO. Patients were followed up from initial TIPS insertion to December 2022 or death. Details of TIPS procedure, adverse events and clinical outcomes were recorded. The cumulative rate of shunt patency was calculated by the Kaplan-Meier method and compared by using the log-rank test. Independent predictors of shunt dysfunction were calculated with the Cox regression model. A nomogram comprising independent variables was developed to enhance the predictive accuracy of shunt patency. RESULTS: One hundred six patients (mean age, 45.3 years ± 13.6; 71 males and 35 females) were enrolled in the study. TIPS procedure was technically successful in 100 of 106 patients (94.3 %). The primary shunt patency rates for all 100 patients were 78.9 %, 74.7 %, 67.2 %, and 62.4 % at 6, 12, 24, and 36 months, respectively, and the overall shunt patency rates were 88.9 %, 86.8 %, 83.6 %, and 81.2 % at 6, 12, 24, and 36 months, respectively. Independent predictor of shunt dysfunction were inadequate inflow from superior mesenteric vein or splenic vein (the maximum diameter < 8 mm) and platelet count ≥ 300 × 109/L. The developed nomogram is a simple tool for accurately predicting shunt patency. CONCLUSIONS: In patients with CPVO, inadequate inflow and high platelet count are important factors for TIPS dysfunction.

A modified model for predicting mortality after transjugular intrahepatic portosystemic shunt: A multicentre study.

BACKGROUND AND AIMS: The transjugular intrahepatic portosystemic shunt has controversial survival benefits; thus, patient screening should be performed preoperatively. In this study, we aimed to develop a model to predict post-transjugular intrahepatic portosystemic shunt mortality to aid clinical decision making. METHODS: A total of 811 patients undergoing transjugular intrahepatic portosystemic shunt from five hospitals were divided into the training and external validation data sets. A modified prediction model of post-transjugular intrahepatic portosystemic shunt mortality (ModelMT ) was built after performing logistic regression. To verify the improved performance of ModelMT , we compared it with seven previous models, both in discrimination and calibration. Furthermore, patients were stratified into low-, medium-, high- and extremely high-risk subgroups. RESULTS: ModelMT demonstrated a satisfying predictive efficiency in both discrimination and calibration, with an area under the curve of .875 in the training set and .852 in the validation set. Compared to previous models (ALBI, BILI-PLT, MELD-Na, MOTS, FIPS, MELD, CLIF-C AD), ModelMT showed superior performance in discrimination by statistical difference in the Delong test, net reclassification improvement and integrated discrimination improvement (all p < .050). Similar results were observed in calibration. Low-, medium-, high- and extremely high-risk groups were defined by scores of ≤160, 160-180, 180-200 and >200, respectively. To facilitate future clinical application, we also built an applet for ModelMT . CONCLUSIONS: We successfully developed a predictive model with improved performance to assist in decision making for transjugular intrahepatic portosystemic shunt according to survival benefits.

6-mm shunt transjugular intrahepatic portosystemic shunt in patients with severe liver atrophy and variceal bleeding.

OBJECTIVES: We proposed a strategy for the creation of a 6-mm transjugular intrahepatic portosystemic shunt (TIPS) and to assess its effectiveness compared to a conventional 8-mm shunt for TIPS-induced hepatic encephalopathy (HE). METHODS: Patients were reviewed retrospectively using propensity score matching (1:1) and divided into 6-mm and 8-mm shunt groups based on shunt diameter. The stent patency, HE incidence, and rebleeding rate between the two groups were then compared. RESULTS: From January 2018 to June 2021, both 6-mm shunt group and 8-mm shunt group included 58 patients. The 6-mm shunt group had significantly smaller liver volumes (879.3 ± 237.1 vs. 1008.8 ± 293.0; p = 0.010), and the median stent patency times were 30.7 and 33.8 months in the 6-mm and 8-mm groups, respectively (p = 0.124). No statistically significant difference was found between the two groups in the 1-year (8.6% vs. 3.4%; p = 0.242) and 2-year (17.2% vs. 12.1%; p = 0.242) rebleeding rates. The 1-year cumulative incidences of overt HE were 12.1% and 27.6% in the 6-mm and 8-mm groups, respectively (p = 0.040), and the 2-year cumulative overt HE incidences in these groups were 19.0% and 36.2%, respectively (p = 0.038). Notably, patients with a 6-mm shunt also experienced less hepatic impairment. CONCLUSIONS: For patients with variceal bleeding and a small liver volume, the 6-mm shunt significantly reduced the incidence of overt HE, protected perioperative liver function, and did not affect stent patency or rebleeding rate. CLINICAL RELEVANCE STATEMENT: For patients with variceal bleeding with small liver volume, the 6-mm transjugular intrahepatic portosystemic shunt (TIPS) significantly reduced the incidence of overt hepatic encephalopathy after TIPS, protected perioperative liver function, and did not affect stent patency and rebleeding rate. KEY POINTS: • A strategy for the creation of a 6-mm transjugular intrahepatic portosystemic shunt for patients with variceal bleeding and a small liver volume was proposed. • The 6-mm transjugular intrahepatic portosystemic shunt significantly reduced the incidence of overt hepatic encephalopathy. • The 6-mm transjugular intrahepatic portosystemic shunt did not affect stent patency or rebleeding rate.

Addition of transarterial chemoembolization improves outcome of tyrosine kinase and immune checkpoint inhibitors regime in patients with unresectable hepatocellular carcinoma.

Background: Transarterial chemoembolization (TACE) is the standard treatment for hepatocellular carcinoma (HCC); the value of its combination with systemic therapy is worthy of further exploration. This study aimed to investigate the efficacy and safety of TACE combined with tyrosine kinase inhibitor (TKI) and immune checkpoint inhibitor (ICI) in the treatment of unresectable HCC. Methods: In this retrospective observational, single-center study, 147 patients with unresectable HCC were divided into a TACE group (n=98) and a non-TACE group (n=49) based on whether TACE was performed during TKI plus ICI therapy. The survival outcomes and adverse events (AEs) of the two groups were compared. Results: Data from patients with unresectable HCC who received TKI plus ICI treatment between July 2017 and April 2020 were collected. The median intrahepatic tumor size was 8.7 cm [interquartile range (IQR), 5.9-12.4 cm]. At data cut-off, overall survival (OS) of the TACE group was significantly longer than that of the non-TACE group (19.5 and 10.8 months, respectively, P=0.005). In the high-risk cohort (with main or contralateral portal vein tumor thrombi and/or bile duct invasion and/or a tumor burden >50% of liver), the OS of the TACE group was still longer than that of the non-TACE group (14.9 and 8.7 months, respectively, P=0.031). Major AEs were tolerated in both groups, and there was no significant difference in their incidence (34.7% and 30.6%, respectively, P=0.621). Conclusions: TACE treatment combined with TKI plus ICI regime resulted in longer OS than treatment with TKI plus ICI alone for patients with unresectable HCC.

TACE Combined with Lenvatinib and Camrelizumab for Unresectable Multiple Nodular and Large Hepatocellular Carcinoma (>5 cm).

BACKGROUND: The incidence and mortality of hepatocellular carcinoma (HCC) had increased globally over the past decades. Previous studies found that transarterial chemoembolization (TACE) combined with lenvatinib had also shown efficacy in the unresectable HCC. We aimed to evaluate the safety and efficacy of TACE combined with lenvatinib and camrelizumab to treat unresectable multiple nodular and large HCC (>5 cm). MATERIALS AND METHODS: Between November 2018 and June 2021, we retrospectively recruited 82 patients with unresectable multiple nodular and large HCC (BCLC stage B or C with a single nodular diameter of >5 cm). Of the patients who had not previously been treated, 33 patients received TACE + lenvatinib + camrelizumab (group A, TLC), and 49 patients treated with TACE + lenvatinib (group B, TLB) as the initial treatment. Related efficacy and safety results were recorded and assessed. RESULTS: The median follow-up periods of groups A and B were 14.5 ± 7.9 months (range, 3-36) and 12.5 ± 8.2 months (range, 3-32), respectively (P = 0.799). The progression-free survival (PFS) of groups A and B was 9.4 months and 5.9 months (P < 0.01), respectively, and overall survival (OS) was significantly longer in group A (16.4 months vs 11.0 months, P < 0.01). In group A, the local response rate (LRR) and disease control rate (DCR) were 51.5% and 81.8%, respectively, which was higher than the corresponding 46.9% and 77.6% observed in group B (P = 0.233; 0.429). Patients with BCLC B stage had better PFS and OS (P < 0.05). The BCLC stage was an independent factor that affected PFS and OS. There were no massive bleeding or treatment-related deaths. CONCLUSIONS: In patients with unresectable multiple nodular and large HCC (single nodular diameter of >5 cm), TACE combined with target therapy and immunotherapy is safe and effective.

3D automatic liver and spleen assessment in predicting overt hepatic encephalopathy before TIPS: a multi-center study.

BACKGROUND: Overt hepatic encephalopathy (HE) should be predicted preoperatively to identify suitable candidates for transjugular intrahepatic portosystemic shunt (TIPS) instead of first-line treatment. This study aimed to construct a 3D assessment-based model to predict post-TIPS overt HE. METHODS: In this multi-center cohort study, 487 patients who underwent TIPS were subdivided into a training dataset (390 cases from three hospitals) and an external validation dataset (97 cases from another two hospitals). Candidate factors included clinical, vascular, and 2D and 3D data. Combining the least absolute shrinkage and operator method, support vector machine, and probability calibration by isotonic regression, we constructed four predictive models: clinical, 2D, 3D, and combined models. Their discrimination and calibration were compared to identify the optimal model, with subgroup analysis performed. RESULTS: The 3D model showed better discrimination than did the 2D model (training: 0.719 vs. 0.691; validation: 0.730 vs. 0.622). The model combining clinical and 3D factors outperformed the clinical and 3D models (training: 0.802 vs. 0.735 vs. 0.719; validation: 0.816 vs. 0.723 vs. 0.730; all p < 0.050). Moreover, the combined model had the best calibration. The performance of the best model was not affected by the total bilirubin level, Child-Pugh score, ammonia level, or the indication for TIPS. CONCLUSION: 3D assessment of the liver and the spleen provided additional information to predict overt HE, improving the chance of TIPS for suitable patients. 3D assessment could also be used in similar studies related to cirrhosis.

Safety, efficacy, and survival of drug-eluting beads-transarterial chemoembolization vs. conventional-transarterial chemoembolization in advanced HCC patients with main portal vein tumor thrombus.

OBJECTIVES: To compare the efficacy, overall survival (OS) and safety of drug-eluting beads-TACE (DEB-TACE) and C-TACE as initial treatment in advanced hepatocellular carcinoma (HCC) patients with main portal vein tumor thrombus (mPVTT). METHODS: The medical records of consecutive advanced HCC patients with mPVTT who underwent initial DEB-TACE or C-TACE from September 2015 to October 2021 were retrospectively evaluated. Treatment crossover was allowed in this retrospective research. The adverse events, disease control rate (DCR), time to tumor progression (TTP) and OS of patients who underwent DEB-TACE were compared with those of patients who underwent C-TACE. RESULTS: Eighty-three patients were included: 42 patients in DEB-TACE group and 41 patients in C-TACE group. DEB-TACE could be safely performed in HCC patients with mPVTT, and they gained a better DCR than those submitted to the C-TACE (76.2% vs. 53.7%, P = 0.031), which might have resulted in longer TTP (median TTP: 9.0 months vs. 3.0 months, P < 0.001). Furthermore, DEB-TACE showed significant OS benefits compared with C-TACE (median OS: 12.0 months vs. 5.0 months, P < 0.001). DEB-TACE, absence of arterioportal shunts (APS), leisons with capsular non-infiltration were found to be independent prognostic factors for better OS. Furthermore, subgroup analysis proved that patients with good DCR gained longer OS in DEB-TACE group. CONCLUSIONS: DEB-TACE could be safely performed and improve the DCR of HCC patients with mPVTT, which resulting in longer TTP and OS, compared with C-TACE.

Screening differential circular RNA expression profiles and the potential role of hsa_circ_0085465 in liver cancer.

Aims: This study aimed to screen the circular RNAs (circRNAs) that are differentially expressed between liver cancer and paired paracarcinoma tissues and then elucidate their role in cancer progression. Materials and Methods: High-throughput sequencing of cancer and paired paracarcinoma tissues was followed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses of the parental genes of the differentially expressed circRNAs, which were also verified via real-time quantitative polymerase chain reaction analysis of the tissues. In addition, the function of selected circRNAs was determined using 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4- sulfophenyl)-2H-tetrazolium (MTS) and transwell assays. Results: Total 218 and 121 circRNAs were differentially upregulated and downregulated, respectively; these were mainly enriched with GO and KEGG terms related to biological functions. From five representatives of the differentially expressed circRNAs, we selected hsa_circ_0085465 for further analysis, discovering that its overexpression promoted the proliferation, migration, and invasion of 97 L cells. Conclusion: Taken together, our results suggest that hsa_circ_0085465 is relevant to liver cancer progression.

Transarterial Chemoembolization Combined with Atezolizumab Plus Bevacizumab or Lenvatinib for Unresectable Hepatocellular Carcinoma: A Propensity Score Matched Study.

Purpose: Combined transarterial chemoembolization (TACE) and Lenvatinib (LEN) treatment (LEN-TACE) has been shown to be beneficial. We aimed to evaluate retrospectively Atezolizumab plus Bevacizumab (Atezo/Bev)-TACE compared with LEN-TACE as a first-line therapy for unresectable HCC. Patients and Methods: From October 2020 to October 2022, data from 98 consecutive HCC patients were analyzed. After propensity score matching, two cohorts of 34 patients who received either Atezo/Bev-TACE or LEN-TACE were studied. We compared overall survival (OS), progression-free survival (PFS), duration of response, objective response rate (ORR) and disease control rate (DCR) based on RECIST 1.1 and mRECIST, as well as safety outcome between the two cohorts. Results: The 6-month and 12-month OS rates were 85.3% (95% CI 73.5-97.0) and 75.4% (95% CI 53.6-85.7) in the Atezo/Bev-TACE group, and 88.2% (95% CI 76.5-97.1) and 79.2% (95% CI 63.6-90.9) in the LEN-TACE group, respectively. The hazard ratio for death in the Atezo/Bev-TACE group compared to the LEN-TACE group was 1.09 (95% CI 0.47-2.51; P = 0.837). The median PFS was 7.03 months (95% CI 3.89-10.17) in the Atezo/Bev-TACE group and 6.03 months (95% CI 0-14.14) in the LEN-TACE group (HR 1.21; 95% CI 0.66-2.21; P = 0.545). No significant difference in ORR and DCR between the two groups was observed either according to RECIST 1.1 or mRECIST standards. Incidence rates of hand-foot skin reaction (35.3% vs 5.9%, P = 0.003) and proteinuria (17.9% vs 2.9%, P = 0.046) were significantly higher in the LEN-TACE group. Conclusion: Atezo/Bev-TACE and LEN-TACE showed comparable efficacy and safety as first-line therapies for unresectable HCC patients.

Idarubicin versus epirubicin in drug-eluting beads-transarterial chemoembolization for treating hepatocellular carcinoma: A real-world retrospective study.

The purpose of this study was to compare the efficacy and safety of idarubicin-loaded drug-eluting beads-transarterial chemoembolization (IDA-TACE) and epirubicin-loaded drug-eluting beads-TACE (EPI-TACE) in treating hepatocellular carcinoma (HCC). All patients with HCC treated with TACE in our hospital between June 2020 and January 2022 were screened. The included patients were divided into the IDA-TACE group and EPI-TACE group to compare overall survival (OS), time to progression (TTP), objective response rate (ORR), and adverse events. There were 55 patients each in the IDA-TACE and EPI-TACE groups. Compared with the EPI-TACE group, the median TTP in the IDA-TACE group was not significantly different (10.50 vs. 9.23 months; HR 0.68; 95% CI 0.40-1.16; P = 0.154), whereas the survival status in the IDA-TACE group tended to be better (neither achieved; HR 0.47; 95% CI 0.22-1.02; P = 0.055). Based on the Barcelona Clinic Liver Cancer staging system for subgroup analysis, considering stage C patients, the IDA-TACE group performed significantly better in terms of ORR (77.1% vs. 54.3%, P = 0.044), median TTP (10.93 vs. 5.20 months; HR 0.46; 95% CI 0.24-0.89; P = 0.021), and median OS (not achieved vs. 17.80 months; HR 0.41; 95% CI 0.18-0.93; P = 0.033). Considering stage B patients, there were no significant differences between the IDA-TACE and EPI-TACE groups in terms of ORR (80.0% vs. 80.0%, P = 1.000), median TTP (10.20 vs. 11.2 months; HR 1.41; 95% CI 0.54-3.65; P = 0.483), or median OS (neither achieved, HR 0.47; 95% CI 0.04-5.24; P = 0.543). Notably, leukopenia was more common in the IDA-TACE group (20.0%, P = 0.052), and fever was more common in the EPI-TACE group (49.1%, P = 0.010). IDA-TACE was more effective than EPI-TACE in treating advanced-stage HCC and comparable in treating intermediate-stage HCC.