Carvedilol has limited research on decompensated cirrhosis. This study compared the effects of carvedilol, traditional nonselective beta blockers (NSBBs), including propranolol and nadolol, and other interventions in patients using carvedilol or traditional NSBBs for secondary prophylaxis of variceal hemorrhage (VH) and portal hypertension (PH)-related complications.

A systematic search of databases, including PubMed, Embase, Cochrane Library, and Scopus, was conducted through October 2023. Randomized controlled trials (RCTs) evaluating carvedilol or traditional NSBBs for secondary prophylaxis of VH were included. The outcomes were the occurrence of VH and portal PH-related complications, including new or worsening ascites, hepatic encephalopathy, spontaneous bacterial peritonitis, and hepatorenal syndrome. A network meta-analysis was performed using a random-effects model.

A total of 60 RCTs involving 5,600 patients with a median Child Pugh score of 8.0 (range 6.8-10) were included. The risk of carvedilol plus variceal band ligation (VBL) on VH was lower than placebo (relative risk (RR) 0.24; 95% confidence interval (CI): 0.10-0.57), and the risk of carvedilol on new or worsening ascites was lower than placebo (RR = 0.10, 95%CI; 0.01-0.93). Traditional NSBBs plus VBL also had preventive effects on VH compared to placebo (RR = 0.31, 95%CI; 0.18-0.54). However, there were no differences between carvedilol and traditional NSBBs in other outcomes.

Carvedilol can prevent PH-related complications, including VH and new or worsening ascites, in cirrhosis patients with a history of VH. No significant differences were observed between the effects of carvedilol and traditional NSBBs, both combined with VBL.

Assess incidence of hepatic encephalopathy (HE) after transjugular intrahepatic portosystemic shunt (TIPS) in patients treated with 8-10 mm Controlled Expansion diameter VIATORR® (VCX) versus 10 mm diameter first-generation VIATORR® (Legacy) stent-grafts.

Single-centre retrospective study (January 2015 to March 2024), including 132 adult patients with cirrhosis treated with TIPS due to complications of portal hypertension. Outcomes included post-TIPS new onset overt HE, ascites response, re-bleeding, mortality and portal pressure gradient (PPG) before and after TIPS. Comparisons used Chi square and Fisher´s exact test for categorical variables and Student´s t test or Mann-Whitney test for quantitative variables.

Indication for TIPS was refractory ascites (n = 82) and variceal bleeding (n = 50). The VCX group (n = 85) and the Legacy group (n = 47) had similar new onset overt HE: 37% (31/85) vs 43% (20/47), respectively (p = 0.31); mortality rates (34% [29/85]) vs 39% [18/47], respectively, p = 0.57) and re-bleeding (17% [6/35] vs 20% [3/15], respectively, p = 1.00). Median PPG reduction after TIPS was 10 mmHg (7 - 13) in the VCX group and 12 mmHg (9 - 15) in the Legacy group (p = 0.02). Subgroup analysis revealed post TIPS overt HE rate of 38% (19/50) in the VCX group vs 53% (17/32) in the Legacy group (p = 0.13), with refractory ascites as an indication. Shunt dysfunction rate was 7% (6/85) in the VCX group (stent thrombosis n = 6, stenosis or malpositioning n = 0) and 0% (0/47) in the Legacy group (p = 0.09).

VCX stent grafts induce an immediate lower PPG reduction, which might lead to more stent dysfunctions, but also to a reduction in post-TIPS HE.

The effect of transjugular intrahepatic portosystemic shunt (TIPS) plus variceal embolization for treating gastric varices (GVs) remains controversial. This nationwide multicenter cohort study aimed to evaluate whether adding variceal embolization to a small diameter (8-mm) TIPS could reduce the rebleeding incidence in patients with different types of GVs.

This retrospective cohort study involved 629 patients who underwent 8-mm TIPS for gastric varices at 7 medical centers. The primary endpoint was all-cause rebleeding, and the secondary endpoints included overt hepatic encephalopathy (OHE) and all-cause mortality.

A total of 629 patients were included. Among them, 429 (68.2%) had gastroesophageal varices type 1 (GOV1), 145 (23.1%) had gastroesophageal varices type 2 (GOV2), and 55 (8.7%) had isolated gastric varices type 1 (IGV1). In the entire cohort, adjunctive embolization reduced rebleeding (6.2% vs 13.6%; P = .005) and OHE (31.0% vs 39.4%; P = .02) compared with TIPS alone. However, no significant differences were found in mortality (12.0% vs 9.7%; P = .42). In patients with GOV2 and IGV1, TIPS plus variceal embolization reduced both rebleeding (GOV2: 7.8% vs 25.1%; P = .01; IGV1: 5.6% vs 30.8%; P = .03) and OHE (GOV2: 31.8% vs 51.5%; P = .008; IGV1: 11.6% vs 38.5%; P = .04). However, in patients with GOV1, adjunctive embolization did not reduce rebleeding (5.9% vs 8.7%; P = .37) or OHE (33.1% vs 35.3%; P = .60).

Compared with TIPS alone, 8-mm TIPS plus variceal embolization reduced rebleeding and OHE in patients with GOV2 and IGV1. These findings suggest that patients with GOV2 and IGV1, rather than GOV1, could benefit from embolization with TIPS.

Despite a better understanding in its prognosis and pathogenesis, hepatic encephalopathy (HE) remains one of the major complications of Transjugular Intrahepatic Portosystemic Shunt (TIPS) with a prevalence ranging from 35 to 50%. Its epidemiology differs according to the indication for TIPS (salvage/rescue TIPS, preemptive (pTIPS) or elective TIPS). In salvage/rescue TIPS, the prognosis is linked to that of bleeding, and HE should not be a contraindication to TIPS, especially as bleeding is a common precipitating factor of HE. In pTIPS, i.e. TIPS performed within the 72 h after stabilization of acute variceal bleeding in high-risk patients, the risk rebleeding and HE is reduced, when compared to endoscopic and drugs treatment. As a consequence, the Baveno VII recommendations state that HE at admission should not be considered as a contraindication to pTIPS placement. In elective situations, such as refractory (intractable ascites (intolerance to diuretics) or resistant ascites (i.e. despite optimal diuretic treatment (spironolactone 400 mg/d and Furosemide 160 mg/d combined with low-salt treatment (< 5.2 g/day) or recurrent ascites (the need for at least 3 paracenteses per year) and secondary prophylaxis of variceal bleeding, it is recommended to systematically look for risk factors for HE, and chronic or refractory HE remain not recommended to TIPS in most centers. Chronic HE involves persistent neurological symptoms with fluctuating acute episodes. Recurrent HE refers to repeated episodes occurring within 6 months, while refractory HE is resistant to standard treatments, often requiring more aggressive management (Vilstrup et al. 2014). A careful selection of patients is mandatory before elective TIPS decision. Risk factors must be identified and corrected if possible before any TIPS decision is made. Management of HE after TIPS is based on identification of precipitating factors, curative treatment with lactulose as first-line therapy and rifaximin as second-line therapy, and nutritional management. In elective TIPS, prophylactic administration of rifaximin is recommended in order to decrease the risk of further HE development in selected patients (not in everyone, at least according to Baveno VII). Liver transplantation (LT) should be discussed with a multidisciplinary team as an alternative option to TIPS in case of high-risk of post-TIPS HE, and in case of refractory HE after TIPS.

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.

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.

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.

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.

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.

ClinicalTrials.gov, ID: NCT03590288.

Clinically significant portal hypertension in patients with liver cirrhosis can lead to refractory ascites. A TIPS treats clinically significant portal hypertension but may cause overt hepatic encephalopathy (oHE). Our aim was to determine the optimal reduction of the portal pressure gradient (PPG) through TIPS to control ascites without raising oHE risk.

This multicenter study screened 1509 patients from 3 European centers (Hannover, Vienna, and Hamburg) undergoing TIPS implantation between 2000 and 2023. Patients with TIPS indications other than refractory ascites/hepatic hydrothorax, vascular liver disease, HCC, or insufficient PPG data were excluded. PPG was measured before and after TIPS insertion. Outcome data were assessed up to 1 year after TIPS insertion. Analyses were conducted utilizing a modern machine learning model, namely a competing-risk random survival forest, partial dependence plots, and competing risk analyses with liver transplantation/death as competitors. The cohort was divided into a 60% derivation and 40% validation cohort. Overall, 729 patients (median MELD: 13 [IQR 10-16], 66% male, 23% oHE before TIPS) were analyzed. The derivation cohort comprised 438 patients, and the validation cohort comprised 291 patients. The optimal PPG reduction, determined by maximally selected Gray statistic and PDP of the random survival forest, was 60%-80%. In this range, patients showed significantly fewer hepatic decompensations due to ascites (HDA) (subdistribution hazard ratio [sHR]: 0.7 [0.52-0.96]) with similar oHE incidences (sHR: 0.92 [0.67-1.27]). The PPG range was confirmed in the validation cohort (HDA: sHR: 0.66 [0.46-0.96]; oHE: sHR: 0.89 [0.61-1.32]).

A targeted PPG reduction of 60%-80% showed significantly reduced HDA without increased oHE risk. Therefore, PPG reduction within this range could be a valid reduction target.

Patients with cirrhosis-associated and portal hypertension-associated complications may benefit from TIPS and/or liver transplantation. In many patients, the decision of whether or not TIPS should be placed prior to liver transplantation is fairly clear-cut. Nevertheless, there are some patients in whom the decision can be more complex. On one hand, TIPS is easily available in contrast to liver transplantation, and patients with TIPS may have clinical improvement. On the other hand, although TIPS may improve the situation of the patient, this improvement may not be sufficient to significantly improve the quality of life. Furthermore, TIPS malposition may be challenging for liver transplantation surgery. This review approaches the advantages and disadvantages of TIPS placement in patients who are candidates for liver transplantation and proposes decision pathways for patients with complications of portal hypertension on the liver transplant waiting list.

Portal hypertension is a hemodynamic abnormality that complicates the course of cirrhosis, as well as other diseases that affect the portal venous circulation. The development of portal hypertension compromises prognosis, especially when it rises above a certain threshold known as clinically significant portal hypertension (CSPH). In the consensus conference on Portal Hypertension promoted by the Spanish Association for the Study of the Liver and the Hepatic and Digestive diseases area of the Biomedical Research Networking Center (CIBERehd), different aspects of the diagnosis and treatment of portal hypertension caused by cirrhosis or other diseases were discussed. The outcome of this discussion was a set of recommendations that achieved varying degrees of consensus among panelists and are reflected in this consensus document. The six areas under discussion were: the relevance of CSPH and the non-invasive methods used for its diagnosis and that of cirrhosis, the prevention of the first episode of decompensation and its recurrence, the treatment of acute variceal bleeding and other complications of portal hypertension, the indications for the use of TIPS, and finally, the diagnosis and treatment of liver vascular diseases.

Portal hypertension is a hemodynamic abnormality that complicates the course of cirrhosis, as well as other diseases that affect the portal venous circulation. The development of portal hypertension compromises prognosis, especially when it rises above a certain threshold known as clinically significant portal hypertension (CSPH). In the consensus conference on Portal Hypertension promoted by the Spanish Association for the Study of the Liver and the Hepatic and Digestive diseases area of the Biomedical Research Networking Center (CIBERehd), different aspects of the diagnosis and treatment of portal hypertension caused by cirrhosis or other diseases were discussed. The outcome of this discussion was a set of recommendations that achieved varying degrees of consensus among panelists and are reflected in this consensus document. The six areas under discussion were: the relevance of clinically significant portal hypertension and the non-invasive methods used for its diagnosis and that of cirrhosis, the prevention of the first episode of decompensation and its recurrence, the treatment of acute variceal bleeding and other complications of portal hypertension, the indications for the use of TIPS, and finally, the diagnosis and treatment of liver vascular diseases.

Transjugular intrahepatic portosystemic shunt (TIPS), a highly effective procedure reducing portal hypertension, has been in use for over seven decades and is now a cornerstone in managing portal hypertension-related complications such as variceal bleeding and ascites. Historically, TIPS has dealt with two main challenges: ensuring stent patency and preventing post-TIPS hepatic encephalopathy. The introduction of PTFE-coated stents markedly reduced the risk of TIPS dysfunction and stent patency is no longer a major concern. However, despite improved patient selection criteria, hepatic encephalopathy continues to be a significant and persistent issue. In addition, the broader application of TIPS in recent decades has brought to light additional, albeit less common, complications, such as post-TIPS heart failure. This review offers a comprehensive overview of TIPS historical evolution, advancements in technique, and its application in the treatment of portal hypertension.

Proposed in the early 1980s as a solution for managing complications of portal hypertension, the percutaneous creation of transjugular intrahepatic portosystemic shunt has consistently gained a central role. Increasingly lower complication rates have been observed thanks to improvements in both technologies and the skills of interventional radiologists.

This document is aimed at interventional radiologists and provides best practice recommendations for transjugular intrahepatic portosystemic shunt creation, describing patient selection, intraprocedural management and follow-up, in addition to recommendations in paediatric settings.

The CIRSE Standards of Practice Committee established a writing group consisting of seven European clinicians with recognised expertise in the creation of transjugular intrahepatic portosystemic shunt. The writing group reviewed the existing literature performing a pragmatic evidence search using PubMed to select relevant publications in the English language and involving human subjects, preferably published from 2009 to 2024. The final recommendations were developed by consensus.

TIPS creation has an established role in the successful management of portal hypertension and its complications. This Standards of Practice document provides up-to-date recommendations for patient selection, materials, its safe performance, and follow-up with complications management.

Portal hypertension leads to hepatic artery dilatation and a higher risk of bleeding. We tried to identify the bleeding risk after gastroesophageal varices (GOV) treatment using hepatic artery diameter of contrast-enhanced CT.

Retrospective retrieval of 258 patients with cirrhosis who underwent contrast-enhanced CT from January 2022 to May 2023 and endoscopy within one month thereafter at Hainan Affiliated Hospital of Hainan Medical University. Cirrhotic patients before GOV treatment were used as the test cohort (n = 199), and cirrhotic patients after GOV treatment were used as the validation cohort (n = 59). The grading and bleeding risk was classified according to the endoscopic findings. Arterial-phase images of contrast-enhanced CT were used for coronal reconstruction, and the midpoint diameter of the hepatic artery was measured on coronal images. The optimal cutoff value for identifying bleeding risk was analyzed and calculated in the test cohort, and its diagnostic performance was evaluated in the validation cohort.

In the test cohort, hepatic artery diameters were significantly higher in high-risk GOV than in low-risk GOV [4.69 (4.31, 5.56) vs. 3.10 (2.59, 3.77), P < 0.001]. With a hepatic artery diameter cutoff value of 4.06 mm, the optimal area under the operating characteristic curve was 0.940 (95% confidence interval: 0.908-0.972), with a sensitivity of 0.887, a specificity of 0.892, a positive predictive value of 0.904, and a negative predictive value of 0.874 for identifying bleeding risk in the test cohort, while in the validation cohort, the sensitivity was 0.885, specificity was 0.939, positive predictive value was 0.920, and negative predictive value was 0.912.

Hepatic artery diameter has high diagnostic performance in identifying bleeding risk after GOV treatment.

Transjugular intrahepatic portosystemic shunt (TIPS) has become essential in the treatment or prevention of portal hypertension-related complications. In the early 1990s, the primary indication was refractory bleeding. It is now proposed for the treatment of ascites for the prevention of bleeding and in patients with vascular diseases of the liver. Thus, there are a growing number of patients being treated with TIPS all over the world. The broadening of indications, the involvement of multiple stakeholders, the need for an accurate selection, the positioning in relation to transplantation and the lack of standardization in pre-therapeutic assessment, in the procedure itself and in the follow-up have led the board of the French Association for the Study of the Liver to establish recommendations.

Liver cirrhosis has long been considered a point of no return, with limited hope for recovery. However, recent advancements, particularly the Baveno VII criteria and the utilization of transjugular intrahepatic portosystemic shunt (TIPS), have illuminated the concept of hepatic recompensation. In this editorial we comment on the article by Gao et al published in the recent issue. This editorial provides a comprehensive overview of the evolution of understanding cirrhosis, the criteria for recompensation, and the efficacy of TIPS in achieving recompensation. We discuss key findings from recent studies, including the promising outcomes observed in patients who achieved recompensation post-TIPS insertion. While further research is needed to validate these findings and elucidate the mech-anisms underlying recompensation, the insights presented here offer renewed hope for patients with decompensated cirrhosis and highlight the potential of TIPS as a therapeutic option in their management.

Measurement of hepatic venous pressure gradient (HVPG) effectively mirrors the severity of portal hypertension (PH) and offers valuable insights into prognosis of liver disease, including the risk of decompensation and mortality. Additionally, HVPG offers crucial information about treatment response to nonselective beta-blockers and other medications, with its utility demonstrated in clinical trials in patients with PH. Despite the widespread dissemination and validation of noninvasive tests, HVPG still holds a significant role in hepatology. Physicians treating patients with liver diseases should comprehend the HVPG measurement procedure, its applications, and how to interpret the results and potential pitfalls.

Decompensated cirrhosis is associated with a significantly increased risk of mortality. Variceal hemorrhage (VH) further increases the risk of mortality, and of future variceal bleed events. Non-selective beta-blockers (NSBBs) are effective therapy for primary and secondary prophylaxis of VH and have become the cornerstone of pharmacologic therapy in cirrhosis. Beta-blockers are associated with reduced overall mortality and GI-bleeding related mortality in patients with decompensated cirrhosis; they may also confer hemodynamically independent beneficial effects. Long-term treatment with beta-blockers may improve decompensation-free survival in compensated cirrhosis with clinically significant portal hypertension (CSPH). Carvedilol more effectively lowers the hepatic vein portal gradient than traditional NSBBs and has been shown to improve survival in compensated cirrhosis. Treatment goals in compensated cirrhosis with CSPH should focus on early utilization of beta-blockers to prevent decompensation and reduce mortality.

Over the past decade, significant advancements in pharmacological, endoscopic, and radiographic treatments have emerged in the management of patients with cirrhosis and esophagogastric varices or variceal hemorrhage. These advances have been in several areas, including the role of screening and primary prophylaxis (preventing an initial variceal bleed), evaluation and management of acute esophagogastric variceal hemorrhage, and in preventing variceal rebleeding. Therefore, we believe there is a need for an updated, evidence-based "narrative review" on this important clinical topic that will be relevant for internists, hospitalists, intensive care unit physicians, and those in training. We believe the guidance presented in this narrative review will enhance daily medical practice of health care professionals and has the potential to improve quality of care for these complex patients.

Cirrhosis is a chronic disease characterized by chronic liver inflammation and diffuse fibrosis. A combination of vasoactive drugs, preventive antibiotics, and endoscopy is the recommended standard treatment for patients with acute variceal bleeding; however, this has been challenged. We compared the effects of early transjugular intrahepatic portosystemic shunt (TIPS), non-early TIPS, and standard treatment in patients with cirrhosis and acute variceal bleeding.

The present network meta-analysis was conducted in accordance with the criteria outlined in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses and Assessing the methodological quality of systematic reviews guidelines. The review has been registered with the International Prospective Register of Systematic Reviews. The PubMed, Embase, Cochrane Library, ClinicalTrials.gov, and World Health Organization-approved trial registry databases were searched for randomized controlled trials (RCTs) evaluating early TIPS, non-early TIPS, and standard treatment in patients with cirrhosis and acute variceal bleeding.

Twenty-four RCTs (1894 patients) were included in the review. Compared with standard treatment, early TIPS [odds ratio (OR), 0.53; 95% credible interval (Cr), 0.30-0.94; surface under the cumulative ranking curve (SUCRA), 98.3] had a lower risk of all-cause mortality (moderate-to-high-quality evidence), and early TIPS (OR, 0.19; 95% CrI, 0.11-0.28; SUCRA, 98.2) and non-early TIPS (OR, 0.30; 95% CrI, 0.23-0.42; SUCRA, 1.8) were associated with a lower risk of rebleeding (moderate-to-high-quality evidence). Early TIPS was not associated with a reduced risk of hepatic encephalopathy, and non-early TIPS (OR, 2.78; 95% CrI, 1.89-4.23, SUCRA, 0) was associated with an increased incidence of hepatic encephalopathy (moderate-to-high-quality evidence). There was no difference in the incidence of new or worsening ascites (moderate-to-high-quality evidence) among the three interventions.

Based on the moderate-to-high quality evidence presented in this study, early TIPS placement was associated with reduced all-cause mortality [with a median follow-up of 1.9 years (25th-75th percentile range 1.9-2.3 years)] and rebleeding compared to standard treatment and non-early TIPS. Although early TIPS and standard treatment had a comparable incidence of hepatic encephalopathy, early TIPS showed superiority over non-early TIPS in this aspect. Recent studies have also shown promising results in controlling TIPS-related hepatic encephalopathy. However, it is important to consider individual patient characteristics and weigh the potential benefits against the risks associated with early TIPS. Therefore, we recommend that clinicians carefully evaluate the patient's condition, considering factors such as severity of variceal bleeding, underlying liver disease, and overall clinical status, before making a treatment decision. Further well-designed RCTs comparing early TIPS with non-early TIPS are needed to validate these findings and provide more definitive guidance.

Nonselective beta-blockers (NSBBs) may exacerbate ascites by impairing cardiac function. This study evaluated the impact of achieving a heart rate target of 55-60 beats per minute (bpm) on ascites-related death and complications from worsening ascites in patients with cirrhosis and diuretic-responsive ascites using NSBBs. A retrospective study was conducted at the Faculty of Medicine Ramathibodi Hospital, Mahidol University (2012-2022) and analyzed patients with cirrhosis and diuretic-responsive ascites using NSBBs (propranolol/carvedilol) for variceal bleeding prophylaxis. The outcomes were incidence of ascites-related death and complications from worsening ascites, comparing the achievable target group (heart rate 55-60 bpm) and the unachievable target group (heart rate >60 bpm). A total of 206 patients were included in the study, with a median follow-up time of 20 months. The patients were divided into an achievable target group (n = 75, median heart rate = 58.0 bpm) and an unachievable target group (n = 131, median heart rate = 73.6 bpm). Propranolol was the most used NSBB (95.1%). The adjusted hazard ratio (HR) for ascites-related death from spontaneous bacterial peritonitis (SBP) or refractory ascites (RA) or hepatorenal syndrome (HRS) or hepatic encephalopathy (HE) showed no difference between the groups (adjusted HR 0.59 [0.23-1.54]; p = 0.28). Additionally, no significant difference was found in the incidence of complications between groups, including SBP, RA, HRS, and HE. Achieving a heart rate target of 55-60 bpm with NSBBs for variceal bleeding prophylaxis is safe in patients with diuretic-responsive ascites and cirrhosis.

Pre-emptive transjugular intrahepatic portosystemic shunt (TIPS) is the treatment of choice for high-risk acute variceal bleeding (AVB; i.e., Child-Turcotte-Pugh [CTP] B8-9+active bleeding/C10-13). Nevertheless, some 'non-high-risk' patients have poor outcomes despite the combination of non-selective beta-blockers and endoscopic variceal ligation for secondary prophylaxis. We investigated prognostic factors for re-bleeding and mortality in 'non-high-risk' AVB to identify subgroups who may benefit from more potent treatments (i.e., TIPS) to prevent further decompensation and mortality.

A total of 2,225 adults with cirrhosis and variceal bleeding were prospectively recruited at 34 centres between 2011-2015; for the purpose of this study, case definitions and information on prognostic indicators at index AVB and on day 5 were further refined in low-risk patients, of whom 581 (without failure to control bleeding or contraindications to TIPS) who were managed by non-selective beta-blockers/endoscopic variceal ligation, were finally included. Patients were followed for 1 year.

Overall, 90 patients (15%) re-bled and 70 (12%) patients died during follow-up. Using clinical routine data, no meaningful predictors of re-bleeding were identified. However, re-bleeding (included as a time-dependent co-variable) increased mortality, even after accounting for differences in patient characteristics (adjusted cause-specific hazard ratio: 2.57; 95% CI 1.43-4.62; p = 0.002). A nomogram including CTP, creatinine, and sodium measured at baseline accurately (concordance: 0.752) stratified the risk of death.

The majority of 'non-high-risk' patients with AVB have an excellent prognosis, if treated according to current recommendations. However, about one-fifth of patients, i.e. those with CTP ≥8 and/or high creatinine levels or hyponatremia, have a considerable risk of death within 1 year of the index bleed. Future clinical trials should investigate whether elective TIPS placement reduces mortality in these patients.

Pre-emptive transjugular intrahepatic portosystemic shunt placement improves outcomes in high-risk acute variceal bleeding; nevertheless, some 'non-high-risk' patients have poor outcomes despite the combination of non-selective beta-blockers and endoscopic variceal ligation. This is the first large-scale study investigating prognostic factors for re-bleeding and mortality in 'non-high-risk' acute variceal bleeding. While no clinically meaningful predictors were identified for re-bleeding, we developed a nomogram integrating baseline Child-Turcotte-Pugh score, creatinine, and sodium to stratify mortality risk. Our study paves the way for future clinical trials evaluating whether elective transjugular intrahepatic portosystemic shunt placement improves outcomes in presumably 'non-high-risk' patients who are identified as being at increased risk of death.

Portal hypertension (PH) constitutes a pivotal factor in the progression of cirrhosis, giving rise to severe complications and a diminished survival rate. The transjugular intrahepatic portosystemic shunt (TIPS) procedure has undergone significant evolution, with advancements in stent technology assuming a central role in managing PH-related complications. This review aims to outline the progression of TIPS and emphasizes the significant influence of stent advancement on its effectiveness. Initially, the use of bare metal stents (BMSs) was limited due to frequent dysfunction. However, the advent of expanding polytetrafluoroethylene-covered stent grafts (ePTFE-SGs) heralded a transformative era, greatly enhancing patency rates. Further innovation culminated in the creation of ePTFE-SGs with controlled expansion, enabling precise adjustment of TIPS diameters. Comparative analyses demonstrated the superiority of ePTFE-SGs over BMSs, resulting in improved patency, fewer complications, and higher survival rates. Additional technical findings highlight the importance of central stent placement and adequate stent length, as well as the use of smaller calibers to reduce the risk of shunt-related complications. However, improving TIPS through technical means alone is inadequate for optimizing patient outcomes. An extensive understanding of hemodynamic, cardiac, and systemic factors is required to predict outcomes and tailor a personalized approach. Looking forward, the ongoing progress in SG technology, paired with the control of clinical factors that can impact outcomes, holds the promise of reshaping the management of PH-related complications in cirrhosis.

The number of complications in patients admitted for cirrhosis has increased over time. Portal hypertension is the driver of many complications of cirrhosis. TIPS placement is the most effective treatment of portal hypertension. The aim of this study was to analyze the use and impact of TIPS placement in the last decade in a nationwide study in Germany.

We analyzed 14,598 admissions of patients for TIPS insertions in Germany from 2007 to 2018 using the DRG system, 12,877 out of 2,000,765 total admissions of patients with cirrhosis. All diagnoses and procedures were coded according to ICD-10-CM and OPS codes. The data were analyzed, focusing on the number of admissions and in-hospital mortality.

The number of TIPS placements increased over the last decade. In-hospital mortality of cirrhotic patients with TIPS decreased when it was placed for severe bleeding (15.2% [TIPS] vs. 19.5% [endoscopy treatment]), ascites (8.7% [TIPS] vs. 14.4% [paracentesis]), and hepatorenal syndrome (HRS) (17.1% [TIPS] vs. 43.3% [no-TIPS]). In the case of bleeding, TIPS significantly decreased in-hospital mortality and also in ascites and HRS. During hospitalization, 22.6% admissions of patients with TIPS insertion showed HE. However, in-hospital mortality in patients admitted with HE grades 1 or 2 and TIPS was lower than in patients without TIPS. In the logistic regression, a higher HE grade(3 and 4), infection, and circulatory disease were found to be independently associated with in-hospital mortality in patients with TIPS insertion.

Our nationwide study demonstrates that TIPS insertion is increasingly used in Germany. TIPS improves outcomes, especially in patients with ascites and HRS, regardless of lower HE grades, while higher HE grades, infection, and circulatory diseases seem to be associated with risk of in-hospital mortality.

Further decompensation represents a prognostic stage of cirrhosis associated with higher mortality compared with first decompensation. A transjugular intrahepatic portosystemic shunt (TIPS) is indicated to prevent variceal rebleeding and for refractory ascites, but its overall efficacy to prevent further decompensations is unknown. This study assessed the incidence of further decompensation and mortality after TIPS vs. standard of care (SOC).

Controlled studies assessing covered TIPS compared with SOC for the indication of refractory ascites and prevention of variceal rebleeding published from 2004 to 2020 were considered. We collected individual patient data (IPD) to perform an IPD meta-analysis and to compare the treatment effect in a propensity score (PS)-matched population. Primary outcome was the incidence of further decompensation and the secondary outcome was overall survival.

In total, 3,949 individual patient data sets were extracted from 12 controlled studies and, after PS matching, 2,338 patients with similar characteristics (SOC = 1,749; TIPS = 589) were analysed. The 2-year cumulative incidence function of further decompensation in the PS-matched population was 0.48 (95% CI 0.43-0.52) in the TIPS group vs. 0.63 (95% CI 0.61-0.65) in the SOC group (stratified Gray's test, p <0.0001), considering mortality and liver transplantation as competing events. The lower further decompensation rate with TIPS was confirmed by adjusted IPD meta-analysis (hazard ratio 0.44; 95% CI 0.37-0.54) and was consistent across TIPS indication subgroups. The 2-year cumulative survival probability was higher with TIPS than with SOC (0.71 vs. 0.63; p = 0.0001).

The use of TIPS for refractory ascites and for prevention of variceal rebleeding reduces the incidence of a further decompensation event compared with SOC and increases survival in highly selected patients.

A further decompensation (new or worsening ascites, variceal bleeding or rebleeding, hepatic encephalopathy, jaundice, hepatorenal syndrome-acute kidney injury and spontaneous bacterial peritonitis) in patients with cirrhosis is associated with a poor prognosis. Besides the known role of TIPS in portal hypertension-related complications, this study shows that TIPS is also able to decrease the overall risk of a further decompensation and increase survival compared with standard of care. These results further support the role of TIPS in the management of patients with cirrhosis and portal hypertension-related complications.

Background Some studies have shown that transjugular intrahepatic portosystemic shunt (TIPS) placement within 72 hours of admission improves survival in patients at high risk who present with acute variceal bleeding. However, the role of small-diameter covered TIPS in the secondary prophylaxis of variceal bleeding is still debatable. Purpose To compare the efficacy of 8-mm TIPS and endoscopic variceal ligation (EVL) plus propranolol in the prevention of variceal rebleeding among participants with advanced cirrhosis. Materials and Methods Between June 2015 and December 2018, participants admitted to the hospital for variceal bleeding were considered for enrollment in this randomized controlled trial (ClinicalTrials.gov). Participants with Child-Pugh class B or C cirrhosis were randomly assigned to receive an 8-mm covered TIPS or EVL and propranolol. The primary end point was recurrent variceal bleeding assessed using Kaplan-Meier curve analysis. Secondary end points included survival and overt hepatic encephalopathy (HE) assessed using Kaplan-Meier curve analysis. Results A total of 100 participants were enrolled, with 50 randomly assigned to the EVL plus propranolol group (median age, 54 years; IQR, 45-60 years; 29 male, 21 female) and 50 randomly assigned to the TIPS group (median age, 49 years; IQR, 43-56 years; 32 male, 18 female). The median follow-up period was 43.4 months. In the TIPS group, variceal rebleeding risk was reduced compared with variceal rebleeding risk in the EVL plus propranolol group (hazard ratio [HR], 0.31; 95% CI: 0.14, 0.69; P = .008), but the incidence of overt HE was higher in the TIPS group (30.0% vs 16.0%, P = .03). No differences in survival were observed between the two groups (1-year survival: TIPS, 98.0%; EVL plus propranolol, 92.0%; 3-year survival: TIPS, 94.0%; EVL plus propranolol, 85.7%; HR, 0.52; 95% CI: 0.19, 1.42; P = .22). Conclusion When compared with EVL plus propranolol, 8-mm TIPS led to reduced variceal rebleeding but did not impact overall survival in participants with Child-Pugh class B or C cirrhosis. Clinical trial registration no. NCT02477384 © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Barth in this issue.

Carvedilol induces stronger decreases in hepatic venous pressure gradient (HVPG) than conventional nonselective β-blockers (ie, propranolol). Limited data exist on the efficacy of carvedilol in secondary prophylaxis of variceal bleeding.

Patients undergoing paired HVPG measurements for guiding secondary prophylaxis with either carvedilol or propranolol were included in this retrospective analysis. All patients also underwent band ligation. Changes in HVPG and systemic hemodynamics were compared between the 2 groups. Long-term follow-up data on rebleeding, acute kidney injury, nonbleeding decompensation, and liver-related death were analyzed applying competing risk regression.

Eighty-seven patients (carvedilol/propranolol, n = 45/42) were included in our study. The median baseline HVPG was 21 mm Hg (interquartile range, 18-24 mm Hg), and 39.1%/48.3%/12.6% had Child-Turcotte-Pugh A/B/C cirrhosis, respectively. Upon nonselective β-blocker initiation, HVPG decreased more strongly in carvedilol users (median relative decrease, -20% [interquartile range: -29% to -10%] vs -11% [-22% to -5%] for propranolol; P = .027), who also achieved chronic HVPG response more often (53.3% vs 28.6%; P = .034). Cumulative incidences for rebleeding (Gray test, P = .027) and liver-related death (P = .036) were significantly lower in patients taking carvedilol compared with propranolol. Notably, ascites development/worsening also was observed less commonly in carvedilol patients (P = .012). Meanwhile, acute kidney injury rates did not differ between the 2 groups (P = .255). Stratifying patients by HVPG response status yielded similar results. The prognostic value of carvedilol intake was confirmed in competing risk regression models.

Carvedilol induces more marked reductions in HVPG than propranolol in secondary prophylaxis of variceal bleeding, and thus is associated with lower rates of rebleeding, liver-related death, and further nonbleeding decompensation.

The primary aim is to estimate the cost-effectiveness of transjugular intrahepatic portosystemic stent shunt (TIPSS) in two indications from a Spanish perspective. Firstly, as pre-emptive treatment for patients with acute variceal bleeding (indication 1) compared with endoscopic band ligation plus drug therapy. Secondly, to treat refractory ascites (indication 2) compared with large volume paracentesis.

A two-state (alive and dead) Markov model was developed to capture the costs and health impact for the two indications over a 2-year time horizon with monthly cycles. In the alive state, patients could experience adverse event(s), associated with costs and disutility, such as recurrent variceal bleeding, ascites, and hepatic encephalopathy. Discount rates of 3% for utilities and costs and a cost-effectiveness threshold of €25,000 per QALY were applied.

In the base case analysis, TIPSS was estimated to be cost-effective as a pre-emptive treatment for indication 1 (incremental cost and QALYs of - €230 and 0.211, respectively). TIPSS also remained cost-effective (€16,819/QALY) in a conservative scenario analysis, conducted with an alternate source for clinical parameters. The key drivers of the outcomes were survival for the comparator arm, mean band ligation outpatient procedures, and TIPSS treatment costs. TIPSS was estimated to dominate the comparator for indication 2 (incremental cost and QALYs of - €25,687 and 0.531, respectively). The key drivers of the outcomes were monthly paracentesis sessions and cost per inpatient stay for those undergoing paracentesis.

TIPSS is likely to be a cost-effective and a cost-saving treatment in patients with cirrhosis in indications 1 and 2, compared with standard treatments. The analyses estimate clinical benefits along with reduced healthcare costs from avoided downstream resource consumption.

It is controversial whether transjugular intrahepatic portosystemic shunt (TIPS) placement can improve long-term survival.

To assess whether TIPS placement improves survival in patients with hepatic-venous-pressure-gradient (HVPG) ≥ 16 mmHg, based on HVPG-related risk stratification.

Consecutive variceal bleeding patients treated with endoscopic therapy + nonselective β-blockers (NSBBs) or covered TIPS placement were retrospectively enrolled between January 2013 and December 2019. HVPG measurements were performed before therapy. The primary outcome was transplant-free survival; secondary endpoints were rebleeding and overt hepatic encephalopathy (OHE).

A total of 184 patients were analyzed (mean age, 55.27 years ± 13.86, 107 males; 102 in the EVL+NSBB group, 82 in the covered TIPS group). Based on the HVPG-guided risk stratification, 70 patients had HVPG < 16 mmHg, and 114 patients had HVPG ≥ 16 mmHg. The median follow-up time of the cohort was 49.5 mo. There was no significant difference in transplant-free survival between the two treatment groups overall (hazard ratio [HR], 0.61; 95% confidence interval [CI]: 0.35-1.05; P = 0.07). In the high-HVPG tier, transplant-free survival was higher in the TIPS group (HR, 0.44; 95%CI: 0.23-0.85; P = 0.004). In the low-HVPG tier, transplant-free survival after the two treatments was similar (HR, 0.86; 95%CI: 0.33-0.23; P = 0.74). Covered TIPS placement decreased the rate of rebleeding independent of the HVPG tier (P < 0.001). The difference in OHE between the two groups was not statistically significant (P = 0.09; P = 0.48).

TIPS placement can effectively improve transplant-free survival when the HVPG is greater than 16 mmHg.

Hepatic encephalopathy (HE) is a complex condition that arises as a complication of chronic liver disease and portosystemic shunting. Its pathophysiology involves several factors, including impaired ammonia metabolism, portosystemic shunting, sarcopenia, and systemic inflammation. The symptoms of HE can vary significantly, with manifestations ranging from subclinical signs to a comatose state. The West Haven classification system is most commonly used to grade the severity of HE. There is a broad differential for the presenting symptomatology of HE and other causes of altered mental status must be excluded during the workup. HE is a well-known complication of transjugular intrahepatic portosystemic shunt (TIPS) placement. Even though newer stent designs help reduce the risk of HE with smaller diameter shunts, it is essential that patients are counseled regarding this potential risk prior to the procedure. Once a diagnosis of HE has been confirmed, the mainstay of therapy is lactulose and rifaximin. In cases where a patient has received a TIPS placement and continues to experience refractory HE despite medical therapy, it may be necessary to consider shunt reduction or closure.

The fragility index (FI) measures the robustness of randomized controlled trials (RCTs). It complements the P value by taking into account the number of outcome events. In this study, the authors measured the FI for major interventional radiology RCTs.

Interventional radiology RCTs published between January 2010 and December 2022 relating to trans-jugular intrahepatic portosystemic shunt, trans-arterial chemoembolization, needle biopsy, angiography, angioplasty, thrombolysis, and nephrostomy tube insertion were analyzed to measure the FI and robustness of the studies.

A total of 34 RCTs were included. The median FI of those studies was 4.5 (range 1-68). Seven trials (20.6%) had a number of patients lost to follow-up that was higher than their FI, and 15 (44.1%) had a FI of 1-3.

The median FI, and hence the reproducibility of interventional radiology RCTs, is low compared to other medical fields, with some having a FI of 1, which should be interrupted cautiously.

In cirrhotic patients, recurrent bleeding after the first episode of esophageal variceal bleeding (EVB) is common and lethal. The present study was aimed to compare balloon-compression endoscopic injection sclerotherapy (bc-EIS) with transjugular intrahepatic portosystemic shunt (TIPS) for the prophylaxis of variceal rebleeding.

Between June 2020 and September 2022, 81 cirrhotic patients with EVB (42 in the bc-EIS group and 39 in the TIPS group) were evaluated retrospectively. The occurrence of rebleeding, hepatic encephalopathy (HE) or other complications, as well as liver functions and survival rate were compared between two groups.

During the 12 months of follow-up, variceal eradication was achieved in 40 (95.24%) patients of the bc-EIS group after a mean of 1.80 ± 0.94 sessions. TIPS was successfully performed in 39 (100%) patients. No significant difference in the variceal rebleeding rate was observed between bc-EIS and TIPS groups (16.67 vs. 17.95%; p = 0.111). While the bc-EIS group showed significantly decreased incidence of HE (2.38 vs. 17.95%; p < 0.001) and lower level of total bilirubin (p < 0.05) in comparison with the TIPS group. The difference in mortality between the two groups failed to reach statistical significance (0.00 vs. 7.69%; p = 0.107).

Bc-EIS is not inferior to TIPS in the survival and control of variceal rebleeding, but associated with decreased risk of HE and liver dysfunction.

Variceal bleeding is a consequence of severe portal hypertension in patients with liver cirrhosis. Although the rate of bleeding has decreased over time, variceal bleeding in the presence of acute-on-chronic liver failure (ACLF) carries a high risk of treatment failure and short-term mortality. Treatment and/or removal of precipitating events (mainly bacterial infection and alcoholic hepatitis) and decrease of portal pressure may improve outcome of patients with acute decompensation or ACLF. Transjugular intrahepatic portosystemic shunts (TIPSs), especially in the preemptive situation, have been found to efficiently control bleeding, prevent rebleeding, and reduce short-term mortality. Therefore, TIPS placement should be considered as an option in the management of ACLF patients with variceal bleeding.