Introduction:Patients with advanced hepatocellular carcinoma (HCC) face an extremely poor prognosis. Sorafenib, a multikinase inhibitor, remains an essential treatment for advanced HCC in certain clinical settings where immunotherapy is either contraindicated or unavailable. However, the survival benefit of transarterial chemoembolization (TACE) plus sorafenib remains under investigation. Methods:The SELECT trial was a multicenter, randomized, controlled study conducted across twelve centers in China. From September 7, 2013, to December 4, 2019, 199 patients with advanced-stage HCC were randomly assigned in a 1:1 ratio to receive either TACE plus sorafenib or sorafenib monotherapy. Results:The median age of the study population was 55 years (IQR 46-63), with hepatic virus infection being the predominant cause of HCC. In the intention-to-treat (ITT) population, the overall survival (OS) analysis did not show a statistically significant difference between the combination and sorafenib monotherapy groups (14.9 months [95% CI: 10.5-19.3] vs. 11.9 months [95% CI: 9.0-14.8], HR 0.862, p = 0.312). However, the combination therapy group demonstrated significantly improved time to progression (TTP) (10.0 months [95% CI: 6.4-13.6] vs. 5.9 months [95% CI: 3.1-8.7]; p = 0.016) and post hoc progression-free survival (PFS) (8.5 months [95% CI: 6.7-10.3] vs. 5.6 months [95% CI: 4.1-7.1]; p = 0.034). In predefined per-protocol analysis, the combination therapy group showed a significantly longer median OS compared to the monotherapy group (14.6 months [11.3-17.9] vs. 7.4 months [95% CI: 4.3-10.5], HR 0.539, p = 0.001). Conclusion:Although the combination of TACE and sorafenib did not demonstrate a significant improvement in OS in the ITT analysis, it met the secondary endpoints, including TTP and post hoc PFS. These findings provide valuable insights for the design of future trials and highlight the importance of integrating locoregional interventions with systemic therapies in the management of advanced-stage HCC.

BACKGROUND & AIMS:Large-scale cohort studies on interventional radiological treatments for Budd-Chiari syndrome (BCS), including percutaneous angioplasty (PTA) with or without routine stenting and transjugular intrahepatic portosystemic shunt (TIPS), are lacking. We aimed to evaluate the long-term outcomes of these treatments in Chinese BCS patients. METHODS:Consecutive patients diagnosed with BCS in 6 Chinese tertiary centers were retrospectively screened for eligibility between January 2010 and May 2019. The roles of the treatment modalities, as well as their associated clinical outcomes, were assessed. RESULTS:Overall, 997 patients were enrolled, with obstruction types classified as inferior vena cava (15.7%), hepatic vein (16.2%), and combined (68.1%). The majority (93.5%) presented with moderate-to-severe symptoms, with 60.7% (n = 607) showing a disease course exceeding 6 months. All patients received anticoagulation, among them, 117 (11.7%) patients underwent medical therapy alone, including 65 asymptomatic or mildly symptomatic patients, and 52 with failed, unfeasible, or declined recanalization; 834 (83.7%) patients successfully recanalized through PTA alone (n = 566) or PTA with routine stenting (n = 268); 90 (9.0%) patients received TIPS placement (comprising 46 initial and 44 converted procedures); and no patients underwent liver transplantation. With a median follow-up of 57.3 months, 103 (10.5%) deaths occurred, primarily from liver failure. The 5-year rates for overall, TIPS-free, stenting-TIPS-free, and intervention-free survival were 90.2% (95% confidence interval [CI]: 88.2%-92.3%), 83.0% (95% CI: 80.5%-85.6%), 59.3% (95% CI: 56.2%-62.6%), and 10.6% (95% CI: 8.8%-12.7%), respectively (P < .001), with consistent outcomes across BCS subtypes. CONCLUSIONS:With predominantly inferior vena cava obstruction presented and recanalization used, interventional radiological treatment could achieve a good long-term outcome in Chinese patients with BCS.

Implantation of irradiation stents demonstrates superiority over conventional metal stents in terms of stent patency and survival for patients with distal malignant biliary obstruction. Here, we aimed to explore the efficacy and advantages of irradiation stents compared with conventional metal stents in patients with unresectable malignant hilar biliary obstruction (MHBO). Unresectable MHBO patients treated with irradiation stents (IS group) were prospectively enrolled and followed up, and patients treated with conventional stents (CS group) were retrospectively enrolled by propensity score matching. The end of the follow-up period was recorded as either the date of death or 2 years after stent implantation. The primary endpoint was stent restenosis, while secondary endpoints included technical success, jaundice remission, complications, and survival. A total of 44 patients were enrolled in this retrospective study (22 in each group). Stents were successfully implanted in all patients. Relief of jaundice was comparable between groups (IS: 81.8

Background & Aims: Pre-emptive transjugular intrahepatic portosystemic shunt (TIPS) improves outcomes in high-risk acute variceal bleeding but its use is limited by hepatic encephalopathy (HE). While stent diameter and post-TIPS portacaval pressure gradient (PPG) targets may influence HE risk, evidence-based standards are lacking. This study aimed to compare 8-mm vs. 10-mm diameter stents and evaluate PPG thresholds to balance HE risk and therapeutic efficacy. Methods: In this multicenter observational study, 470 patients with cirrhosis and acute variceal bleeding receiving pre-emptive TIPS (8-mm: n = 384; 10-mm: n = 86) were analyzed. Competing risks regression and restricted cubic splines were used to assess associations between stent diameter, PPG, and clinical outcomes. Results: At 1 year, 8-mm stents reduced overt HE incidence (28.9% vs. 45.4%; subdistribution hazard ratio [sHR] 0.57, 95% CI 0.40–0.82) and further decompensation (40.4% vs. 52.3%; sHR 0.68, 95% CI 0.48–0.95) compared to 10-mm stents, without increasing the risk of further bleeding (12.0% vs. 9.3%; p = 0.471) or mortality (13.3% vs. 14.0%; p = 0.813). Non-linear analysis identified a PPG range of 7–13 mmHg associated with minimized overt HE risks (sHR 1.43 for PPG <7 vs. 7–13 mmHg; 95% CI 1.01–2.01) and portal hypertensive complications (sHR 2.76 for PPG >13 vs. 7–13 mmHg; 95% CI 2.69–9.39). A significantly greater proportion of patients in the 8-mm group attained the optimal 7–13 mmHg target range compared to the 10-mm group (71.1% vs. 55.8%, p <0.001). Conclusions: Pre-emptive TIPS with 8-mm stents reduces HE and further decompensation without compromising efficacy. Immediate post-TIPS PPG measurements may aid intraprocedural decision-making, with a 7–13 mmHg range serving as a pragmatic guide for initial stent calibration in high-risk acute variceal bleeding. Impact and implications: This multicenter study of 470 patients with cirrhosis and acute variceal bleeding shows that pre-emptive transjugular intrahepatic portosystemic shunt (TIPS) placement using 8-mm stents reduces the 1-year incidence of overt hepatic encephalopathy by 43% compared to 10-mm stents, while maintaining similar efficacy in preventing rebleeding. Non-linear analysis identified a post-TIPS portacaval pressure gradient (PPG) range of 7–13 mmHg as an optimal target, minimizing risks of both overt hepatic encephalopathy and portal hypertensive complications. A significantly higher proportion of patients achieved this PPG range with 8-mm stents. These results address a key dilemma in high-risk AVB management, demonstrating that 8-mm stents balance encephalopathy prevention with effective portal decompression. The 7–13 mmHg PPG range provides a practical intraprocedural guide for individualized TIPS calibration, helping interventional radiologists optimize shunt diameter selection.

BACKGROUND AND AIMS:A recanalisation-specific model for Budd-Chiari syndrome (BCS) is lacking. We aimed to develop a novel score for individual long-term outcome prediction and risk stratification. METHODS:Overall, 834 BCS patients undergoing recanalisation (566 received percutaneous transluminal angioplasty alone, and 268 with routine stenting) from January 2010 to May 2019 were included from six Chinese centres. The model was developed using Cox multivariable regression, internally validated through a 1000-times bootstrapped method, and compared its performance with existing BCS prognostic models, like the Clichy score. RESULTS:During the median follow-up period of 58.0 months, 44 patients were converted to transjugular intrahepatic portosystemic shunt (TIPS), none underwent orthotopic liver transplantation (OLT) and 75 died. The final BCS-Recanalisation score incorporated: variceal bleeding history, degree of ascites, albumin, creatinine, urea, white blood cell count and Ln (alkaline phosphatase). The score outperformed other available models with good discrimination (C-index: 0.74) and calibration in predicting TIPS-free survival in the whole cohort, internal validation and most subgroups. Moreover, patients were categorised as low-risk (BCS-Recanalisation score ≤ 2.0), intermediate-risk (2.0-2.6) and high-risk (> 2.6) groups using X-tile software, with a 5-year TIPS-free survival rate of 92.2% (95% CI: 89.5%-95.0%), 84.7% (95% CI: 80.0%-90.0%) and 67.8% (95% CI: 59.4%-77.5%), respectively (p < 0.001). Significant differences were observed in overall survival, stenting-TIPS-free survival and competing-risk adjusted outcomes (restenosis, symptom recurrence, TIPS conversion) across risk strata. CONCLUSIONS:The BCS-Recanalisation score enables individualised outcome prediction and risk stratification in recanalisation-treated patients with BCS, showing promise for clinical application. Future external validation is required.

The progression pattern of tumors has an impact on the survival of patients with advanced hepatocellular carcinoma (HCC) and has been applied in the design of clinical trials for multiple second-line drugs. Previous research results have been contradictory, and the clinical impact of different progression patterns and their role in survival are still in question.PurposeThe study aims to analyze the impact of different progression patterns and tumor burden size on survival of HCC patients, as well as their interactions, through a retrospective cohort study.Patients and methodsThe study involved 538 patients who had undergone treatment with sorafenib and had shown radiographic progression. The progression pattern was analyzed using Cox regression by including an interaction term between progression pattern and tumor burden, which was then visualized through a graphical analysis. Tumor burden was categorized into low, medium, and high subgroups based on the six-and-twelve criteria, allowing for an exploration of the effect of progression pattern on survival in different tumor burden situations.ResultsCompared to patients with only intrahepatic progression (NIH/IHG) with an overall survival (OS) of 14.1/19.9 months and post-progression survival (PPS) of 8.1/13.1 months respectively, patients with extrahepatic lesions (NEH/EHG) had worse overall and postprogressive survival (OS: 9.3/9.2 months, PPS: 4.9/5.1 months). The hazard ratio for extrahepatic progression (NEH/EHG) compared to intrahepatic progression (NIH/IHG) at low, medium, and high tumor burden were [HR 2.729, 95%CI 1.189-6.263], [HR 1.755, 95%CI 1.269-2.427], and [HR 1.117, 95%CI 0.832-1.499], respectively.ConclusionThe study concluded that the interaction between the tumor progression patterns and tumor burden significantly affects the prognosis of HCC patients. As the tumor burden increases, the sensitivity of the patient’s risk of death to the progression pattern decreases. These findings are valuable in personalized treatment and trial design.

BACKGROUND & AIMS:The optimal timing of measurement and hemodynamic targets of portacaval pressure gradient (PPG) after transjugular intrahepatic portosystemic shunt (TIPS) placement remain unclear. This study aimed to identify the ideal moment for hemodynamic measurements and the optimal target of PPG in patients undergoing covered TIPS for variceal bleeding. METHODS:Between May 2018 and December 2021, 466 consecutive patients with recurrent variceal bleeding treated with covered TIPS were prospectively included. Post-TIPS PPG was measured immediately (immediate PPG), 24-72 hours (early PPG), and again 1 month (late PPG) after TIPS placement. The agreement among PPGs measured at different time points was assessed by intra-class correlation coefficient (ICC) and Bland-Altman method. The unadjusted and confounder-adjusted effects of PPGs on clinical outcomes (portal hypertensive complications [PHCs], overt hepatic encephalopathy [OHE], further decompensation, and death) were assessed using Fine and Gray competing risk regression models. RESULTS:The agreement between early PPG and late PPG (ICC: 0.34) was better than that between immediate PPG and late PPG (ICC: 0.23, p <0.001). Early PPG revealed an excellent predictive value for PHCs (early PPG≥ vs. <12 mmHg: adjusted hazard ratio 2.17, 95% CI 1.33-3.55, p = 0.002) and OHE (0.40, 95% CI 0.17-0.91, p = 0.030), while immediate PPG did not. Late PPG showed a predictive value for PHC risk but not OHE. By targeting the lowest risk of further decompensation, we identified an optimal hemodynamic target with early PPG ranging from 11 to 14 mmHg that was associated with a decreased risk of OHE and effective prevention of PHCs. CONCLUSIONS:PPG measured 24 to 72 hours after TIPS correlates with long-term PPG and clinical outcomes, and a hemodynamic target PPG of 11-14 mmHg is associated with reduced encephalopathy but not compromised clinical efficacy. IMPACT AND IMPLICATIONS:The optimal timing of measurement and hemodynamic targets of portacaval pressure gradient (PPG) after transjugular intrahepatic portosystemic shunt (TIPS) remain unclear. Here we show that post-TIPS PPG measured at least 24 hours but not immediately after the procedure correlated with long-term PPG and clinical events. Thus, PPG measurements taken at least 24 hours after TIPS should be used to guide decision making in order to improve clinical outcomes. Targeting a post-TIPS PPG of 11-14 mmHg or a 20%-50% relative reduction from pre-TIPS baseline measured 24-72 hours after the procedure was associated with reduced encephalopathy but not compromised clinical efficacy. Thus, these criteria could be used to guide TIPS creation and revision in patients with cirrhosis and variceal bleeding undergoing covered TIPS. CLINICAL TRIAL REGISTRATION NUMBER:ClinicalTrials.gov, ID: NCT03590288.

Background & Aims:Current prognostic models for patients with hepatocellular carcinoma (HCC) undergoing transarterial chemoembolization (TACE) are not extensively validated and widely accepted. We aimed to develop and validate a continuous model incorporating tumor burden and biology for individual survival prediction and risk stratification. Methods:Overall, 4,377 treatment-naive candidates for whom TACE was recommended, from 39 centers in five countries, were enrolled and divided into training, internal validation, and two external validation datasets. The novel model was developed using a Cox multivariable regression analysis and compared with our original 6-and-12 model (the largest tumor size [ts, centimetres] + tumor number [tn]) and other available models in terms of predictive accuracy. Results:The proposed model, named the '6-and-12 model 2.0', was generated as 'ts + tn + 1.5×log10 alpha-fetoprotein (AFP)', showed good discrimination (C-index 0.674) and calibration (Hosmer-Lemeshow test p = 0.147), and outperformed current existing models. An easy-to-use stratification was proposed according to the different AFP levels (≤100, 100-400, 400-2,000, 2,000-10,000, 10,000-40,000, and >40,000 ng/ml) along with the corresponding tumor burden cutoffs (8/14, 7/13, 6/12, 5/11, 4/10, and any tumor burden); that is, if the AFP level was 400-2,000 ng/ml, the stratification should be low-(≤6)/intermediate-(6-12)/high-risk (>12) strata. Hence, it could divide the patients into three distinct risk categories with a median overall survival of 45.0 (95% CI, 40.1-49.9), 30.0 (95% CI, 26.1-33.9), and 15.4 (95% CI, 13.4-17.4) months (p <0.001) from low-risk to high-risk strata, respectively. These findings were confirmed in validation and subgroup analyses. Conclusions:The 6-and-12 model 2.0 significantly improved individual outcome predictions and better stratified the candidates recommended for TACE; thus, this model could be used in both clinical practice and trial design. Impact and implications:In this international multicentre study, we developed and internally and externally validated a novel outcome prediction model for candidates with HCC who would be ideal for TACE. The model, called the 6-and-12 model 2.0, was based on 4,377 patients from 39 centers in five countries. The model offers individualized outcome prediction, outperforming the original 6-and-12 model score and other existing metrics across all datasets and subsets. Based on different levels of alpha-fetoprotein (AFP) and corresponding cut-offs of tumor burden, patients could be stratified into three risk strata with significantly different survival prognoses, which could provide a referential framework to control study heterogeneity and define the target population in future trial designs.

PDF file - 2971K, Supplementary Fig. 2: Kaplan-Meier curves comparing survival between responders and non-responders according (D) RECIST, (E) EASL, and (F) mRECIST assessed at second follow-up after treatment. Abbreviations: EASL, European Association for the Study of the Liver; mRECIST, modified RECIST; RECIST, response evaluation criteria in solid tumors.

Background and Aim: Baveno VII workshop recommends the use of preemptive TIPS (p-TIPS) in patients with cirrhosis and acute variceal bleeding (AVB) at high- risk of treatment failure. However, the criteria defining “high-risk” have low clinical accessibility or include subjective variables. We aimed to develop and externally validate a model for better identification of p-TIPS candidates. Approach and Results: The derivation cohort included 1554 patients with cirrhosis and AVB who were treated with endoscopy plus drug (n = 1264) or p-TIPS (n = 290) from 12 hospitals in China between 2010 and 2017. We first used competing risk regression to develop a score for predicting 6-week and 1-year mortality in patients treated with endoscopy plus drugs, which included age, albumin, bilirubin, international normalized ratio, white blood cell, creatinine, and sodium. The score was internally validated with the bootstrap method, which showed good discrimination (6 wk/1 y concordance-index: 0.766/0.740) and calibration, and outperformed other currently available models. In the second stage, the developed score was combined with treatment and their interaction term to predicate the treatment effect of p-TIPS (mortality risk difference between treatment groups) in the whole derivation cohort. The estimated treatment effect of p-TIPS varied substantially among patients. The prediction model had good discriminative ability (6 wk/1 y c -for-benefit: 0.696/0.665) and was well calibrated. These results were confirmed in the validation dataset of 445 patients with cirrhosis with AVB from 6 hospitals in China between 2017 and 2019 (6-wk/1-y c-for-benefit: 0.675/0.672). Conclusions: We developed and validated a clinical prediction model that can help to identify individuals who will benefit from p-TIPS, which may guide clinical decision-making.

PDF file - 1413K, Supplementary Fig. 3: Among the subgroup of patients with CR (n=18) based on the enhancement criteria, survival was compared between the patients with a PR (n=7) and SD (n=11) after re-classification based on RECIST. Abbreviations: CR, complete response; PR, partial response; SD, stable disease; RECIST, response evaluation criteria in solid tumors.

PDF file - 40K, Supplementary Table 1. Overall response Determined with Evaluation of Target, Nontarget, and New Lesions.

Baveno VII workshop recommends management of acute variceal bleeding (AVB) in cirrhotic patients with nonmalignant portal vein thrombosis (PVT) should be performed according to the guidelines for patients without PVT. Nevertheless, whether PVT affects the outcome of patients with cirrhosis and AVB remains unclear. The aim of this study was to assess the clinical impact of PVT on the outcomes in the pre-emptive TIPSS eligible patients with cirrhosis and AVB. From December 2010 to June 2016, 1219 consecutive cirrhotic patients admitted due to AVB with (n = 151; 12.4

PDF file - 2489K, Supplementary Fig. 1: Kaplan-Meier curves comparing survival between responders and non-responders according (A) RECIST, (B) EASL, and (C) mRECIST assessed at first follow-up after treatment. Abbreviations: EASL, European Association for the Study of the Liver; mRECIST, modified RECIST; RECIST, response evaluation criteria in solid tumors.

Background & AimsAmong individuals with Child-Pugh B cirrhosis and acute variceal bleeding (AVB), the Baveno VII workshop recommended pre-emptive TIPS in those with a Child-Pugh score of 8-9 and active bleeding at initial endoscopy (Child B8-9 + AB criteria). Nevertheless, whether this criterion is superior to the CLIF-Consortium acute decompensation score (CLIF-C ADs) remains unclear.MethodsData on 1,021 consecutive individuals with Child-Pugh B cirrhosis and AVB from 13 university hospitals in China who were treated with pre-emptive TIPS (n = 297) or drug plus endoscopic treatment (n = 724) between 2010 to 2019 were retrospectively analysed. A competing risk regression model was used to compare the outcomes between the two groups after adjusting for confounders. The concordance-statistic for benefit (c-for-benefit) was used to evaluate a models’ ability to predict treatment benefit (risk difference between treatment groups).ResultsPre-emptive TIPS was associated with reduced mortality compared to drug plus endoscopic treatment (adjusted hazard ratio 0.62, 95% CI 0.44 to 0.88). A higher baseline CLIF-C AD score was associated with greater survival benefit (i.e., larger absolute mortality risk reduction). After adjusting for confounders, a survival benefit was observed in individuals with CLIF-C ADs ≥48 or Child-Pugh B8-9 with active bleeding, but not in those with CILF-C ADs <48, no active bleeding or Child-Pugh B7 with active bleeding. The c-for-benefit of CILF-C ADs for predicting survival benefit was higher than that of Child B8-9+AB criteria.ConclusionsIn individuals with Child-Pugh B cirrhosis and AVB, CLIF-C ADs predicts survival benefit from pre-emptive TIPS and outperforms the Child B8-9+AB criteria. Prospective validation should be performed to confirm this result, especially for other aetiologies of cirrhosis.Impact and implicationsIn this study, among individuals with Child-Pugh B cirrhosis and acute variceal bleeding, the CLIF-Consortium acute decompensation (CLIF-C AD) score could predict the survival benefit from pre-emptive TIPS, with patients with higher CLIF-C AD scores benefiting more from pre-emptive TIPS. Furthermore, the CLIF-C AD score outperformed the Child B8-9 plus active bleeding criteria in terms of discriminating between those who obtained more benefit vs. less benefit from pre-emptive TIPS. Depending on prospective validation, the CLIF-C AD score could be used as the model of choice to determine who should undergo pre-emptive TIPS.

BACKGROUND:The role of variceal embolisation at the time of transjugular intrahepatic portosystemic shunt (TIPS) creation for the prevention of gastro-oesophageal variceal rebleeding remains controversial. This study aimed to evaluate whether adding variceal embolisation to TIPS placement could reduce the incidence of rebleeding after TIPS in patients with cirrhosis. METHODS:We did an open-label, randomised controlled trial at one university hospital in China. Eligible patients were aged 18-75 years with cirrhosis and had variceal bleeding in the past 6 weeks, and they were randomly assigned (1:1) to receive TIPS (with a covered stent in both groups) plus variceal embolisation (TIPS plus embolisation group) or TIPS alone (TIPS group) to prevent variceal rebleeding. Randomisation was done using a web-based randomisation system using a Pocock and Simon's minimisation method, stratified by Child-Pugh class (A vs B vs C). Clinicians and patients were not masked to treatment allocation; individuals involved in data analysis were masked to treatment assignment. The primary endpoint was the 2-year cumulative incidence of variceal rebleeding after randomisation, and analysis was by intention to treat. The trial is registered with ClinicalTrials.gov, NCT02119988. FINDINGS:Between June 16, 2014, and Feb 3, 2016, 205 patients were screened, of whom 134 were randomly allocated to the TIPS plus embolisation group (n=69) and the TIPS group (n=65). TIPS placement and variceal embolisation was successful in all 134 patients, all were included in the analysis. There was no significant difference in the 2-year cumulative incidence of variceal rebleeding between the two groups (TIPS plus embolisation 11·6% [95% CI 4·0-19·1] vs TIPS 13·8% [5·4-22·2]; hazard ratio 0·82 [95% CI 0·42-1·61]; p=0·566). Adverse events were similar between the two groups; the most common adverse events were peptic ulcer or gastritis (12 [17%] of patients in the TIPS plus embolisation group vs 13 [20%] of patients in the TIPS group), new or worsening ascites (ten [14%] vs six [9%]), and hepatocellular carcinoma (four [6%] vs six [9%]). The numbers of deaths were also similar between groups (24 [35%] vs 25 [38%]) INTERPRETATION: Adding variceal embolisation to TIPS did not significantly reduce the incidence of variceal rebleeding in patients with cirrhosis. Our findings do not support concomitant variceal embolisation during TIPS for the prevention of variceal rebleeding. FUNDING:National Key Technology R&D Program, Boost Program of Xijing Hospital, and China Postdoctoral Science Foundation.

Background & Aims: Hepatic encephalopathy (HE) is a major complication after transjugular intrahepatic portosystemic shunt (TIPS) and is primarily influenced by the gut microbiota. We aimed to evaluate alterations in the microbiota after TIPS and the association between such alterations and HE. Methods: We conducted a prospective longitudinal study of 106 patients with cirrhosis receiving TIPS. Faecal samples were collected before and after TIPS, and the gut microbiota was analysed by 16S ribosomal RNA sequencing. Results: Among all patients, 33 developed HE (HE+ group) within 6 months after TIPS and 73 did not (HE-group), and 18 died during follow-up. After TIPS, the autochthonous taxa increased, whereas the potential pathogenic taxa decreased in the HE group, and the autochthonous taxon Lachnospiraceae decreased in the HE+ group. Furthermore, synergism among harmful bacteria was observed in all patients, which was weakened in the HE-group (p <0.001) but enhanced in the HE+ group (p <0.01) after TIPS. Variations of 5 autochthonous taxa, namely, Coprococcus, Ruminococcus, Blautia, Ruminococcaceae_uncultured, and Roseburia, were negatively correlated with the severity of HE. Notably, increased abundances of Coprococcus and Ruminococcus were protective factors against HE, and the incidences of HE in patients with improved, stable, and deteriorated microbiota after TIPS were 13.3, 25.9, and 68.2%, respectively. Higher total bilirubin level, Child-Pugh score, model for end stage liver disease score, Granulicatella, and Alistipes and lower Subdoligranulum before TIPS were the independent risk factors for death. Conclusions: Alterations in gut dysbiosis were negatively related to the occurrence and severity of post-TIPS HE, and the pre TIPS microbiota were associated with death, suggesting the gut microbiota could be a promising potential biological target for screening suitable patients receiving TIPS and prevention and treatment of post-TIPS HE.