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.

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.

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.

Inflammation-related nomogram for predicting survival of patients with unresectable hepatocellular carcinoma received conversion therapy.

BACKGROUND: The efficacy of conversion therapy for patients with unresectable hepatocellular carcinoma (HCC) is a common clinical concern. AIM: To analyse the prognostic factors of overall survival (OS) in patients with unresectable HCC who received conversion therapy. METHODS: One hundred and fifty patients who met the inclusion criteria were enrolled and divided into a training cohort (n = 120) and a validation cohort (n = 30). Using the independent risk factors in the training cohort, a nomogram model was constructed to predict OS for patients treated with transarterial chemoembolization following hepatic resection. The nomogram was internally validated with the bootstrapping method. The predictive performance of nomogram was assessed by Harrell's concordance index (C-index), calibration plot and time-dependent receiver operating characteristic curves and compared with six other conventional HCC staging systems. RESULTS: Multivariate Cox analysis identified that albumin, blood urea nitrogen, gamma-glutamyl transpeptidase to platelet ratio, platelet to lymphocyte ratio, macrovascular invasion and tumour number were the six independent prognostic factors correlated with OS in nomogram model. The C-index in the training cohort and validation cohort were 0.752 and 0.807 for predicting OS, which were higher than those of the six conventional HCC staging systems (0.563 to 0.715 for the training cohort and 0.458 to 0.571 for the validation cohort). The calibration plots showed good consistency between the nomogram prediction of OS and the actual observations of OS. Decision curve analyses indicated satisfactory clinical utility. With a total nomogram score of 196, patients were accurately classified into low-risk and high-risk groups. Furthermore, we have deployed the model into online calculators that can be accessed for free at https://ctmodelforunresectablehcc.shinyapps.io/DynNomapp/. CONCLUSION: The nomogram achieved optimal individualized prognostication of OS in HCC patients who received conversion therapy, which could be a useful clinical tool to help guide postoperative personalized interventions and prognosis judgement.

DEM-TACE as the initial treatment could improve the clinical efficacy of the hepatocellular carcinoma with portal vein tumor thrombus: a retrospective controlled study.

BACKGROUND: Conventional-transarterial chemoembolization (C-TACE) was proven to improve overall survival (OS) in hepatocellular carcinoma (HCC) patients with portal vein tumor thrombus (PVTT), drug-eluting microsphere-TACE (DEM-TACE) was supposed to provide more benefit than C-TACE in this respect. PURPOSE: To compare the safety and efficacy between DEM-TACE and C-TACE as the initial treatment in HCC patients with PVTT and to identify prognostic factors of OS. METHODS: The medical records of advanced HCC patients with PVTT who underwent DEM-TACE or C-TACE as the initial thearpy from September 2015 with mean follow-up time 14.9 ± 1.2 (95% CI 12.6-17.2) months were retrospectively evaluated. A total of 97 patients were included, 49 patients in the DEM-TACE group and 48 in the C-TACE group. Adverse events (AEs) related to TACE were compared. Tumor and PVTT radiologic response, time to tumor progression (TTP) and OS were calculated and compared in both groups. RESULTS: Patients in DEM-TACE group had a better radiologic response (Tumr response: 89.8% vs. 75.0%; PVTT response: 85.7% vs. 70.8%; overall response: 79.6% vs. 58.3%, P = 0.024) and longer TTP (7.0 months vs. 4.0 months, P = 0.040) than patients in C-TACE group. A lower incidence of abdominal pain was found in the DEM-TACE group than in C-TACE group (21 vs. 31, P = 0.032), but there were no significant differences between DEM-TACE and C-TACE patients in any other AEs reported. When compared to C-TACE, DEM-TACE also showed significant OS benefits (12.0 months vs. 9.0 months, P = 0.027). DEM-TACE treatment, the absence of arterioportal shunt (APS), lower AFP value and better PVTT radiologic response were the independent prognostic factors for OS in univariate/multivariate analyses, which provided us with a guide for better patient selection. CONCLUSIONS: Based on our retrospective study, DEM-TACE can be performed safely and might be superior to C-TACE as the initial treatment for HCC patients with PVTT. TRIAL REGISTRATION: Retrospectively registered.

Preoperative prediction of overt hepatic encephalopathy caused by transjugular intrahepatic portosystemic shunt.

PURPOSE: Preoperative prediction of overt hepatic encephalopathy (OHE) should be performed in patients with variceal bleeding treated using the transjugular intrahepatic portosystemic shunt (TIPS) procedure. A reliable prediction tool is therefore required. METHOD: Patients with cirrhosis-related variceal bleeding treated using the TIPS procedure were screened at two hospitals. Patients classified as Child-Pugh Class B were identified. The least absolute shrinkage and selection operator method and the backward stepwise selection method were used to screen the clinical and radiological characteristics of participants. Then, models were constructed accordingly to predict OHE. Area under the receiver operating characteristic curves, calibration curves, and decision curves were performed to discover the optimal model. Finally, whether clinical factors influenced the performance of our optimal model was tested. RESULTS: A total of 191 patients were included (training cohort: 127 cases; validation cohort: 64 cases). Three novel radiological independent risk factors were found. The combined model outperformed the models containing clinical factors or radiological characteristics alone. The areas under the curve for the training and validation cohorts were 0.901 and 0.903, respectively, with satisfactory calibration and decision curves. The Model for End-Stage Liver Disease score, serum sodium, albumin, total bilirubin, and age exhibited limited influence on the performance of the combined model. CONCLUSIONS: These radiological characteristics are also independent risk factors for post-TIPS OHE. Combining clinical factors and radiological characteristics was an effective means of predicting OHE. This study's model could be used for preoperative selection of appropriate patients before the TIPS procedure is performed.

Identification of circRNAs involved in the development of hepatocellular carcinoma after insufficient radiofrequency ablation.

Previous studies have reported that circular RNAs (circRNAs) play a key role in the pathogenesis and progression of various diseases. In the present study, we aimed to identify potential circRNAs associated with the progression of hepatocellular carcinoma (HCC) after insufficient radiofrequency ablation (IRFA). A xenograft mouse IRFA model was initially established, and immunohistochemical staining (IHC) and polymerase chain reaction (PCR) were performed to confirm the expression of programmed cell death-ligand 1 (PD-L1) and vascular endothelial growth factor receptor-1 (VEGFR-1). CircRNA expression alterations were screened by next-generation sequencing (RNA-seq). Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were conducted to predict the function of genes coding differentially expressed circRNAs. The selected circRNAs were validated utilizing PCR and Sanger sequencing. The relationships between circRNAs, microRNAs, PD-L1, and VEGFR-1 were predicted by bioinformatics. Overall, a total of 612 circRNAs were differentially expressed in IRFA-treated subcutaneous tumorigenesis tissue. Among them, 435 circRNAs were significantly upregulated and 177 circRNAs were downregulated. GO and KEGG analyses were employed to predict the functions of these circRNAs. Thereafter, quantitative reverse transcription PCR (qRT-PCR) assays determined that these seven circRNAs were overexpressed in the IRFA group, which was consistent with the RNA-seq results. Based on the bioinformatic analysis, seven circRNAs confirmed by Sanger sequencing were predicted to likely regulate PD-L1 and VEGFR-1 expression levels by functioning as sponges for microRNAs (miRNAs) and forming a circRNA-miRNA-PD-L1/VEGFR-1 regulatory network. Finally, IHC and qRT-PCR of PD-L1 and VEGFR-1 confirmed the activation of this pathway. Taken together, we report that differentially expressed circRNAs might simultaneously regulate PD-L1 and VEGFR-1 in the IRFA tissues, which provides a novel view of circRNAs in HCC progression after the IRFA procedure.

Transjugular intrahepatic portosystemic shunt versus endoscopic therapy for prevention of variceal rebleeding in patients with hepatocellular carcinoma meeting the Milan criteria.

OBJECTIVE: Transjugular intrahepatic portosystemic shunt (TIPS) and endoscopic therapy (ET) have been recommended to prevent variceal rebleeding due to cirrhotic portal hypertension. However, which one is better for patients with hepatocellular carcinoma (HCC) remains controversial. Hence, we aimed to compare the clinical outcomes of these two treatments for these subpopulation. METHODS: This retrospective study was approved by the institutional review board. The data of 98 consecutive patients with HCC meeting the Milan criteria (mean age 54.1 years) who had received TIPS placement (34 patients) or ET (64 patients) between June 2010 and December 2017 were reviewed. The clinical outcomes were evaluated and were calculated by the Kaplan-Meier method and compared by using the log-rank test. A matched cohort composed of 34 patients from each group was selected after adjustment with propensity score matching to verify the robustness of the results. RESULTS: The median follow-up time was 33.1 months. The rebleeding rate was significantly lower in TIPS group (P = 0.016). A matched cohort composed of 34 patients from each group after adjustment with propensity score matching showed that TIPS reduced the risk of rebleeding (P = 0.030) without increasing long-term overt hepatic encephalopathy (P = 0.151), while there was no significant difference in overall liver transplant-free survival (P = 0.120). Thereafter, 25 patients in TIPS group (73.5%) and 42 patients in ET group (65.6%) received locoregional therapies for HCC (P = 0.431). CONCLUSION: TIPS reduced the risk of rebleeding without improving survival. Locoregional therapies can be performed safely to manage HCC after sufficient prevention of variceal rebleeding.

Application of percutaneous transluminal sharp recanalization in transjugular intrahepatic portosystemic shunt for patients with chronic portal vein occlusion.

PURPOSE: We aimed to evaluate the feasibility and safety of a modified technique for portal vein recanalization, percutaneous transluminal sharp recanalization (PTSR), when performing transjugular intrahepatic portosystemic shunt (TIPS) for the treatment of chronic portal vein occlusion (CPVO) and portal hypertension. METHODS: Nine consecutive patients with CPVO and portal hypertension had undergone TIPS and PTSR procedure after failing in conventional percutaneous catheterization from March 2017 to July 2019. Technical success rates, effectiveness, and complications were evaluated. Follow-up of patients' clinical outcomes and shunt patency were performed periodically. Primary and secondary shunt patency were analyzed by Kaplan-Meier method. RESULTS: The occluded portal veins were successfully recanalized after failing in conventional percutaneous catheterization, and TIPS procedures were completed in all 9 patients. Two patients suffered from procedure-related complications. A portosystemic pressure gradient <12 mmHg, or a percent reduction of 25% to 50% of baseline, was achieved in all 9 patients after TIPS. During the median follow-up period of 28 months (range, 9-36 months), 1 patient experienced recurrent ascites and the other 8 patients remained asymptomatic. The cumulative rates of primary and secondary shunt patency were 66.67% and 100%, respectively, at 2 years. CONCLUSION: As a supplementary method, PTSR is a feasible and safe method for portal vein recanalization when performing TIPS for patients with CPVO and portal hypertension.

Identifying optimal candidates for early TIPS among patients with cirrhosis and acute variceal bleeding: a multicentre observational study.

OBJECTIVES: Early placement of transjugular intrahepatic portosystemic shunt (TIPS) has been shown to improve survival in high-risk patients (Child-Pugh B plus active bleeding at endoscopy or Child-Pugh C 10-13) with cirrhosis and acute variceal bleeding (AVB). However, early TIPS criteria may overestimate the mortality risk in a significant proportion of patients, and the survival benefit conferred by early TIPS in such patients has been questioned. Alternative criteria have been proposed to refine the criteria used to identify candidates for early TIPS. Nevertheless, the true survival benefit provided (or not) by early TIPS compared with standard treatment in the different risk categories has not been investigated in specifically designed comparative studies. DESIGN: We collected data on 1425 consecutive patients with cirrhosis and AVB who were admitted to 12 university hospitals in China between December 2010 and June 2016. Of these, 206 patients received early TIPS, and 1219 patients received standard treatment. The Fine and Gray competing risk regression model was used to compare the outcomes between the two groups that were stratified based on the currently available risk stratification systems after adjusting for liver disease severity and other potential confounders. RESULTS: Overall, early TIPS was associated with an 80% relative risk reduction (RRR) in mortality at 6 weeks (adjusted HR=0.20; 95% CI: 0.10 to 044; p<0.001) and 51% RRR at 1 year (adjusted HR=0.49, 95% CI: 0.32 to 0.73; p<0.001) compared with standard treatment. In stratification analyses, the RRRs in mortality did not significantly differ among the risk categories. However, the absolute risk reductions (ARRs) of mortality were more pronounced in high-risk patients. The ARRs at 6 weeks were -2.1%, -10.2% and -32.4% in Model for End-stage Liver Disease (MELD) ≤11, 12-18 and ≥19 patients and were -1.5%, -9.1% and -23.2% in Child-Pugh A, B and C patients, respectively (interaction tests, p<0.001 for both criteria). The ARRs for mortality at 1 year were -1.7%, -5.4% and -32.7% in MELD ≤11, 12-18 and ≥19 patients, respectively, and -3.6%, -5.2% and -20.3% in Child-Pugh A, B and C patients, respectively (interaction tests, p<0.001 for both criteria). After adjusting for liver disease severity and other potential confounders, a survival benefit was observed in MELD ≥19 or Child-Pugh C patients but not in MELD ≤11 or Child-Pugh A patients. In MELD 12-18 patients, a survival benefit was observed within 6 weeks but not at 1 year. In Child-Pugh B patients, a survival benefit was observed in those with active bleeding but not those without active bleeding. However, the evaluation of active bleeding was associated with a high interobserver variability. Furthermore, early TIPS was associated with a significantly reduced incidence of failure to control bleeding or rebleeding and new or worsening ascites, without increasing the risk of overt hepatic encephalopathy. CONCLUSIONS: Early TIPS was associated with improved survival in patients with MELD ≥19 or Child-Pugh C cirrhosis but not in patients with MELD ≤11 or Child-Pugh A cirrhosis. For MELD 12-18 or Child-Pugh B patients, future studies addressing optimal selection criteria for early TIPS remain highly warranted.

Percutaneous transhepatic intrahepatic portosystemic shunt for variceal bleeding with chronic portal vein occlusion after splenectomy.

OBJECTIVES: The purpose of this study was to introduce a modified transjugular intrahepatic portosystemic shunt (TIPS), a percutaneous transhepatic intrahepatic portosystemic shunt (PTIPS), and to evaluate its feasibility and efficacy in patients with variceal bleeding with chronic portal vein occlusion (CPVO) after splenectomy. METHODS: Twenty-four cirrhotic patients with CPVO after splenectomy who received PTIPS between 2010 and 2015 were included in this retrospective study. The indication was elective control of variceal bleeding. Success rates, effectiveness and complications were evaluated, with comparison of the pre- and post-portosystemic pressure gradient (PPG). Patients' clinical outcomes and shunt patency were followed periodically. RESULTS: PTIPS was successfully placed in 22 patients (91.7%) and failed in two. The mean PPG fell from 22.0 ± 4.9 mmHg to 10.6 ± 1.6 mmHg after successful PTIPS (p < 0.05). No fatal procedural complications occurred. During the median follow-up of 29 months, shunt dysfunction occurred in five cases and hepatic encephalopathy in four cases. Three patients died because of rebleeding, hepatic failure and pulmonary disease, respectively. The other patients remained asymptomatic and the shunts patent. CONCLUSIONS: We conclude that PTIPS, as a modified TIPS procedure with a high success rate, is safe and effective for variceal bleeding with CPVO after splenectomy. KEY POINTS: • Portal vein occlusion used to be contraindication to transjugular intrahepatic portosystemic shunt. • Portal vein thrombosis is common in patients with previous splenectomy. • We developed a new method, percutaneous transhepatic intrahepatic portosystemic shunt (PTIPS). • PTIPS is feasible in patients with portal vein thrombosis and splenectomy. • PTIPS is effective and safe for these kind of complicated portal hypertension.