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Background and Aims: Data about the prognosis of salvage transjugular intrahepatic portosystemic shunt (TIPS) using covered stents for refractory variceal bleeding caused by portal hypertension are scarce. We aimed to assess survival and to identify predictors of mortality in these patients., Approach and Results: One hundred sixty-four patients with cirrhosis from five centers treated with salvage TIPS between 2007 and 2017 were retrospectively divided into a derivation cohort (83 patients) and a validation cohort (81 patients). Comparisons were performed using the Mann-Whitney and Fischer's exact test. Six-week overall survival (OS) was correlated with variables on the day of the TIPS using Kaplan-Meier curves with log-rank test and univariate/multivariate analyses using the Cox model. Eighty-three patients were included in the derivation cohort (male, 78%; age, 55 years, alcohol-associated cirrhosis, 88%; Model for End-Stage Liver Disease [MELD], 19 [15-27]; arterial lactate, 3.7 mmol/L [2.0-8.3]). Six-week OS rate was 58%. At multivariate analysis, the MELD score (OR, 1.064; 95% CI, 1.005-1.126; P = 0.028) and arterial lactate (OR, 1.063; 95% CI, 1.013-1.114; P = 0.032) were associated with 6-week OS. Six-week OS rates were 100% in patients with arterial lactate ≤2.5 mmol/L and MELD score ≤ 15 and 5% in patients with lactate ≥12 mmol/L and/or MELD score ≥ 30. The 81 patients of the validation cohort had similar MELD and arterial lactate level but lower creatinine level (94 vs 106 µmol/L, P = 0.008); 6-week OS was 67%. Six-week OS rates were 86% in patients with arterial lactate ≤2.5 mmol/L and MELD score ≤ 15 and 10% for patients with lactate ≥12 mmol/L and/or MELD score ≥ 30. In the overall cohort, rebleeding rate was 15.8% at 6 weeks, and the acute-on-chronic liver failure grade (OR, 1.699; 95% CI, 1.056-1.663; P = 0.040) was independently associated with rebleeding., Conclusions: After salvage TIPS, 6-week mortality remains high and can be predicted by MELD score and lactate. Survival rate at 6 weeks was >85% in patients with arterial lactate ≤2.5 mmol/L and MELD score ≤ 15, while mortality was >90% for lactate ≥12 mmol/L and/or MELD score ≥ 30., (© 2021 by the American Association for the Study of Liver Diseases.)

Background & Aims: The relationship between acute-on-chronic liver failure (ACLF) and acute variceal bleeding (AVB) is poorly understood. Specifically, the prevalence and prognosis of ACLF in the context of AVB is unclear, while the role of transjugular intrahepatic portosystemic shunt (TIPS) in the management in patients with ACLF has not been described to date., Methods: A multicenter, international, observational study was conducted in 2,138 patients from 34 centers between 2011 and 2015. ACLF was defined and graded according to the EASL-CLIF consortium definition. Placement of pre-emptive TIPS (pTIPS) was based on individual center policy. Patients were followed-up for 1 year, until death or liver transplantation. Cox regression and competing risk models (Gray's test) were used to identify independent predictors of rebleeding or mortality., Results: At admission, 380/2,138 (17.8%) patients had ACLF according to EASL-CLIF criteria (grade 1: 38.7%; grade 2: 39.2%; grade 3: 22.1%). The 42-day rebleeding (19% vs. 10%; p <0.001) and mortality (47% vs. 10%; p <0.001) rates were higher in patients with ACLF and increased with ACLF grades. Of note, the presence of ACLF was independently associated with rebleeding and mortality. pTIPS placement improved survival in patients with ACLF at 42 days and 1 year. This effect was also observed in propensity score matching analysis of 66 patients with ACLF, of whom 44 received pTIPs and 22 did not., Conclusions: This large multicenter international real-life study identified ACLF at admission as an independent predictor of rebleeding and mortality in patients with AVB. Moreover, pTIPS was associated with improved survival in patients with ACLF and AVB., Lay Summary: Acute variceal bleeding is a deadly complication of liver cirrhosis that results from severe portal hypertension. This study demonstrates that the presence of acute-on-chronic liver failure (ACLF) is the strongest predictor of mortality in patients with acute variceal bleeding. Importantly, patients with ACLF and acute variceal (re)bleeding benefit from pre-emptive (early) placement of a transjugular intrahepatic portosystemic shunt., Competing Interests: Conflict of interest Christophe Bureau has received speaker fees from GORE and is a board member of Alfawassemran/Norgine. Virginia Hernández - Gea, Álvaro Giráldez, Jaume Bosch, Agustin Albillos, Dominique Thabut, Michael Praktiknjo and Frederik Nevens have received speaker fees from GORE. Juan Carlos Garcia – Pagan has received consultant fees from GORE, Shionogi and Cook grants from GORE and Novartis. Jonel Trebicka has received speaking and/or consulting fees from GORE, Bayer, Alexion, MSD, Gilead, Intercept, Norgine, Grifols, Versantis, and Martin Pharmaceutical, and Rafael Bañares has received speaker fees from GORE and Grifols, unrelated to the submitted work. Please refer to the accompanying ICMJE disclosure forms for further details., (Copyright © 2020 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Patients admitted with acute variceal bleeding (AVB) and Child-Pugh C score (CP-C) or Child-Pugh B plus active bleeding at endoscopy (CP-B+AB) are at high risk for treatment failure, rebleeding, and mortality. A preemptive transjugular intrahepatic portosystemic shunt (p-TIPS) has been shown to improve survival in these patients, but its use in clinical practice has been challenged and not routinely incorporated. The present study aimed to further validate the role of preemptive TIPS in a large number of high-risk patients. This multicenter, international, observational study included 671 patients from 34 centers admitted for AVB and high risk of treatment failure. Patients were managed according to current guidelines, and use of drugs and endoscopic therapy (D+E) or p-TIPS was based on individual center policy. p-TIPS in the setting of AVB is associated with a lower mortality in CP-C patients compared with D+E (1 year mortality 22% vs. 47% in D+E group; P = 0.002). Mortality rate in CP-B+AB patients was low, and p-TIPS did not improve it. In CP-C and CP-B+AB patients, p-TIPS reduced treatment failure and rebleeding (1-year cumulative incidence function probability of remaining free of the composite endpoint: 92% vs. 74% in the D+E group; P = 0.017) and development of de novo or worsening of previous ascites without increasing rates of hepatic encephalopathy. Conclusion: p-TIPS must be the treatment of choice in CP-C patients with AVB. Because of the strong benefit in preventing further bleeding and ascites, p-TIPS could be a good treatment strategy for CP-B+AB patients., (© 2018 by the American Association for the Study of Liver Diseases.)

Endoscopic variceal ligation plus beta-blockers (EVL+BB) is currently recommended for variceal rebleeding prophylaxis, a recommendation that extends to all patients with cirrhosis with previous variceal bleeding irrespective of prognostic stage. Individualizing patient care is relevant, and in published studies on variceal rebleeding prophylaxis, there is a lack of information regarding response to therapy by prognostic stage. This study aimed at comparing EVL plus BB with monotherapy (EVL or BB) on all-source rebleeding and mortality in patients with cirrhosis and previous variceal bleeding stratified by cirrhosis severity (Child A versus B/C) by means of individual time-to-event patient data meta-analysis from randomized controlled trials. The study used individual data on 389 patients from three trials comparing EVL plus BB versus BB and 416 patients from four trials comparing EVL plus BB versus EVL. Compared with BB alone, EVL plus BB reduced overall rebleeding in Child A (incidence rate ratio 0.40; 95% confidence interval, 0.18-0.89; P = 0.025) but not in Child B/C, without differences in mortality. The effect of EVL on rebleeding was different according to Child (P for interaction <0.001). Conversely, compared with EVL, EVL plus BB reduced rebleeding in both Child A and B/C, with a significant reduction in mortality in Child B/C (incidence rate ratio 0.46; 95% confidence interval, 0.25-0.85; P = 0.013)., Conclusion: Outcomes of therapies to prevent variceal rebleeding differ depending on cirrhosis severity: in patients with preserved liver function (Child A), combination therapy is recommended because it is more effective in preventing rebleeding, without modifying survival, while in patients with advanced liver failure (Child B/C), EVL alone carries an increased risk of rebleeding and death compared with combination therapy, underlining that BB is the key element of combination therapy. (Hepatology 2017;66:1219-1231)., (© 2017 by the American Association for the Study of Liver Diseases.)

Unlabelled: Balloon tamponade is recommended only as a "bridge" to definitive therapy in patients with cirrhosis and massive or refractory esophageal variceal bleeding (EVB), but is frequently associated with rebleeding and severe complications. Preliminary, noncontrolled data suggest that a self-expandable, esophageal covered metal stent (SX-ELLA Danis; Ella-CS, Hradec Kralove, Czech Republic) may be an effective and safer alternative to balloon tamponade. We conducted a randomized, controlled trial aimed at comparing esophageal stent versus balloon tamponade in patients with cirrhosis and EVB refractory to medical and endoscopic treatment. Primary endpoint was success of therapy, defined as survival at day 15 with control of bleeding and without serious adverse events (SAEs). Twenty-eight patients were randomized to Sengstaken-Blakemore tube (n = 15) or SX-ELLA Danis stent (n = 13). Patients were comparable in severity of liver failure, active bleeding at endoscopy, and initial therapy. Success of therapy was more frequent in the esophageal stent than in balloon tamponade group (66% vs. 20%; P = 0.025). Moreover, control of bleeding was higher (85% vs. 47%; P = 0.037) and transfusional requirements (2 vs 6 PRBC; P = 0.08) and SAEs lower (15% vs. 47%; P = 0.077) in the esophageal stent group. TIPS was used more frequently in the tamponade group (4 vs. 10; P = 0.12). There were no significant differences in 6-week survival (54% vs. 40%; P = 0.46)., Conclusion: Esophageal stents have greater efficacy with less SAEs than balloon tamponade in the control of EVB in treatment failures. Our findings favor the use of esophageal stents in patients with EVB uncontrolled with medical and endoscopic treatment. (Hepatology 2016;63:1957-1967)., (© 2015 by the American Association for the Study of Liver Diseases.)

Unlabelled: Recent studies have shown that liver cirrhosis (LC) behaves as an acquired hypercoagulable state with increased thrombotic risk. This is why anticoagulation therapy (AT) is now frequently used in these patients. Variceal bleeding is a severe complication of LC. It is unknown whether AT may impact the outcome of bleeding in these patients. Fifty-two patients on AT with upper gastrointestinal bleeding (UGIB) were evaluated. Portal vein thrombosis (PVT) and different cardiovascular disorders (CVDs) were the indication for AT in 14 and 38 patients, respectively. Overall, 104 patients with LC and UGIB not under AT matched for severity of LC, age, sex, source of bleeding, and Sequential Organ Failure Assessment (SOFA) score served as controls. UGIB was attributed to portal hypertension (PH) in 99 (63%) patients and peptic/vascular lesions in 57 (37%). Twenty-six (17%) patients experienced 5-day failure; SOFA, source of UGIB, and PVT, but not AT, were independent predictors of 5-day failure. In addition, independent predictors of 6-week mortality, which was observed in 26 (11%) patients, were SOFA, Charlson Comorbidity index, and use of AT for a CVD. There were no differences between patients with/without AT in needs for rescue therapies, intensive care unit admission, transfusions, and hospital stay., Conclusions: Factors that impact the outcome of UGIB in patients under AT are degree of multiorgan failure and comorbidity, but not AT itself., (© 2015 by the American Association for the Study of Liver Diseases.)

According to their location, gastric varices (GV) are classified as gastroesophageal varices and isolated gastric varices. This review will mainly focus on those GV located in the fundus of the stomach (isolated gastric varices 1 and gastroesophageal varices 2). The 1-year risk of GV bleeding has been reported to be around 10%-16%. Size of GV, presence of red signs, and the degree of liver dysfunction are independent predictors of bleeding. Limited data suggest that tissue adhesives, mainly cyanoacrylate (CA), may be effective and better than propranolol in preventing bleeding from GV. General management of acute GV bleeding must be similar to that of esophageal variceal bleeding, including prophylactic antibiotics, a careful replacement of volemia, and early administration of vasoactive drugs. Small sample-sized randomized controlled trials have shown that tissue adhesives are the therapy of choice for acute GV bleeding. In treatment failures, transjugular intrahepatic portosystemic shunt (TIPS) is considered the treatment of choice. After initial hemostasis, repeated sessions with CA injections along with nonselective beta-blockers are recommended as secondary prophylaxis; whether CA is superior to TIPS in this scenario is not completely clear. Balloon-occluded retrograde transvenous obliteration (BRTO) has been introduced as a new method to treat GV. BRTO is also effective and has the potential benefit of increasing portal hepatic blood flow and therefore may be an alternative for patients who may not tolerate TIPS. However, BRTO obliterates spontaneous portosystemic shunts, potentially aggravating portal hypertension and its related complications. The role of BRTO in the management of acute GV bleeding is promising but merits further evaluation., (Copyright © 2014 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Variceal bleeding is one of the commonest and most severe complications of liver cirrhosis. Even with the current best medical care, mortality from variceal bleeding is still around 20%. When cirrhosis is diagnosed, varices are present in about 30-40% of compensated patients and in 60% of those who present with ascites. Once varices have been diagnosed, the overall incidence of variceal bleeding is in the order of 25% at two years. Variceal size is the most useful predictor for variceal bleeding, other predictors are severity of liver dysfunction (Child-Pugh classification) and the presence of red wale marks on the variceal wall. The current consensus is that every cirrhotic patient should be endoscopically screened for varices at the time of diagnosis to detect those requiring prophylactic treatment. Non-selective beta-adrenergic blockers (NSBB) and endoscopic band ligation (EBL) have been shown effective in the prevention of first variceal bleeding. The current recommendation for treating acute variceal bleeding is to start vasoactive drug therapy early (ideally during the transferral or to arrival to hospital, even if active bleeding is only suspected) and performing EBL. Once bleeding is controlled, combination therapy with NSBB + EBL should be used to prevent rebleeding. In patients at high risk of treatment failure despite of using this approach, an early covered-TIPS within 72 h (ideally 24 h) should be considered. Data on management of gastric variceal bleeding is limited. No clear recommendation for primary prophylaxis can be done. In acute cardiofundal variceal bleeding, vasoactive agents together with cyanoacrylate (CA) injection seem to be the treatment of choice. Further CA injections and/or NSBB may be used to prevent rebleeding. TIPS or Balloon-occluded retrograde transvenous obliteration when TIPS is contraindicated may be used as a rescue therapy., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Background & Aims: In a recent randomized international clinical trial (RCT) in high-risk cirrhotic patients with acute variceal bleeding, the early use of transjugular intrahepatic portosystemic shunt (TIPS) was associated with marked and significant reductions in both treatment failure and mortality. The aim of this study was to confirm these results in clinical practice in the same centers of the RCT study., Methods: We retrospectively reviewed patients admitted for acute variceal bleeding and high risk of treatment failure (Child C <14 or Child B plus active bleeding), treated with early-TIPS (n=45) or drugs+endoscopic therapy (ET) (n=30)., Results: Patients treated with early-TIPS had a much lower incidence of failure to control bleeding or rebleeding than patients receiving drug+ET (3 vs. 15; p <0.001). The 1-year actuarial probability of remaining free of this composite end point was 93% vs. 53% (p <0.001). The same was observed in mortality (1-year actuarial survival was 86% vs. 70% respectively; p=0.056). Actuarial curves of failure to control bleeding+rebleeding and of survival were well within the confidence intervals of those observed in the RCT., Conclusions: This study supports the early use of TIPS in patients with cirrhosis and a high-risk variceal bleeding., (Copyright © 2012 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

The evidence that endoscopic band ligation (EBL) has greater efficacy and fewer side effects than endoscopic injection sclerotherapy has renewed interest in endoscopic treatments for portal hypertension. The introduction of multishot band devices, which allow the placement of 5-10 bands at a time, has made the technique much easier to perform, avoiding the use of overtubes and their related complications. EBL sessions are usually repeated at 2 week intervals until varices are obliterated, which is achieved in about 90% of patients after 2-4 sessions. Variceal recurrence is frequent, with 20-75% of patients requiring repeated EBL sessions. According to current evidence, nonselective beta-blockers are the preferred treatment option for prevention of a first variceal bleed, whereas EBL should be reserved for patients with contraindications or intolerance to beta-blockers. Nonselective beta-blockers, probably in association with the vasodilator isosorbide mononitrate, and EBL are good treatment options to prevent recurrent variceal rebleeding. The efficacy of EBL might be increased by combining it with beta-blocker therapy. Patients who are intolerant, have contraindications or bled while receiving primary prophylaxis with beta-blockers must be treated with EBL. In the latter situation, EBL should be added to rather than replace beta-blocker therapy. EBL, in combination with vasoactive drugs, is the recommended form of therapy for acute esophageal variceal bleeding; however, endoscopic injection sclerotherapy can be used in the acute setting if EBL is technically difficult.

Background: Sclerotherapy has been widely recommended as initial treatment for prevention of variceal rebleeding. The present study was aimed at comparing the efficacy of endoscopic sclerotherapy and long-term administration of propranolol in the prevention of rebleeding and long-term survival in patients who had bled from varices., Methods: One hundred sixteen consecutive cirrhotic patients admitted because of variceal bleeding were randomly allocated to either continuous administration of propranolol to reduce the resting heart rate by 25% (58 patients) or weekly intravariceal sclerotherapy sessions using 5% ethanolamide oleate until varices disappeared (58 patients). Results were analyzed on an intention-to-treat basis., Results: Rebleeding occurred in 37 patients of the propranolol group and in 26 patients of the sclerotherapy group (RR = 1.45; 95% CI, 1.03-2.03). The actuarial probability of rebleeding was lower in the sclerotherapy group (P = 0.02). No differences were found in rebleeding index, hospitalization requirements, survival, and causes of death. Complications were significantly more frequent and severe in the sclerotherapy group., Conclusions: Despite the higher efficacy of sclerotherapy decreasing the probability of rebleeding when compared with propranolol, no beneficial effects were observed on other parameters also reflecting the efficacy of therapy. Moreover, complications of sclerotherapy were more frequent and severe than those of propranolol, which probably shall restrict the use of long-term elective sclerotherapy.