Prevention Of Variceal Rebleeding Research Articles

Prevention of variceal rebleeding in cirrhotic patients with spontaneous portosystemic shunts: transjugular intrahepatic portosystemic shunt versus endoscopic treatment.

Spontaneous portosystemic shunts(SPSSs) in cirrhotic patients indicate higher incidence of gastric varices, which increases the risk for bleeding and death. However, few studies compared endoscopic therapy with transjugular intrahepatic portosystemic shunt (TIPS) in preventing variceal rebleeding in cirrhotic patients with SPSSs. This research aims to evaluate the effectiveness of the two methods in this group of patients. We reviewed consecutive cirrhotic patients with SPSSs who underwent either TIPS or endoscopic treatment to prevent variceal rebleeding between January 2015 and December 2018 in our institution. Outcomes including rebleeding, overt hepatic encephalopathy (OHE), complications and survival were compared. Meanwhile, subgroup analyses were conducted to screen relevant factors affecting the results. A total of 97 patients were included in the study. The TIPS arm contained 50 patients and the endoscopy arm contained 47 patients. Rebleeding rate in TIPS group was statistically lower than endoscopic group [16.0 vs 38.3%, hazard ratio (HR) = 0.37, 95% confidence interval (CI): 0.16-0.84, P = 0.01], while OHE was more frequent (16.0 vs 2.1%, HR = 7.59, 95% CI: 0.94-61.2, P = 0.025), the survival rate (92 vs 89.4%, HR = 0.88, 95% CI: 0.22-3.60, P = 0.87) and frequency of complications were comparable between two groups. In the subgroups of GOV2/IGV1 and splenorenal shunt/gastrorenal shunt, compared with endoscopic treatments, TIPS reduced the rate of rebleeding without significantly increasing overt hepatic encephalopathy; however, it did not improve survival rate. For cirrhotic patients with SPSSs, TIPS brought a lower rebleeding rate but a higher incidence of OHE. However, in the subgroups of GOV2/IGV1 and splenorenal shunt/gastrorenal shunt, TIPS was considered more reasonable due to the lower rebleeding rate and comparable OHE incidence.

The Use of Rifaximin in the Prevention of Overt Hepatic Encephalopathy After Transjugular Intrahepatic Portosystemic Shunt : A Randomized Controlled Trial.

The efficacy of rifaximin in the secondary prevention of overt hepatic encephalopathy (HE) is well documented, but its effectiveness in preventing a first episode in patients after transjugular intrahepatic portosystemic shunt (TIPS) has not been established. To determine whether rifaximin prevents overt HE after TIPS compared with placebo. Randomized, double-blind, multicenter, placebo-controlled trial. (ClinicalTrials.gov: NCT02016196). 197 patients with cirrhosis undergoing TIPS for intractable ascites or prevention of variceal rebleeding. Patients were randomly assigned to receive rifaximin (600 mg twice daily) or placebo, beginning 14 days before TIPS and continuing for 168 days after the procedure. The primary efficacy end point was incidence of overt HE within 168 days after the TIPS procedure. An episode of overt HE occurred in 34% (95% CI, 25% to 44%) of patients in the rifaximin group (n = 93) and 53% (CI, 43% to 63%) in the placebo group (n = 93) during the postprocedure period (odds ratio, 0.48 [CI, 0.27 to 0.87]). Neither the incidence of adverse events nor transplant-free survival was significantly different between the 2 groups. The study's conclusion applies mainly to patients with alcoholic cirrhosis, who made up the study population. The potential benefit of rifaximin 6 months after TIPS and beyond remains to be investigated. In patients with cirrhosis treated with TIPS, rifaximin was well tolerated and reduced the risk for overt HE. Rifaximin should therefore be considered for prophylaxis of post-TIPS HE. French Public Health Ministry.

Retrograde transvenous obliteration for the prevention of variceal rebleeding in patients with portal vein thrombosis: a multicenter study.

To evaluate the effectiveness of retrograde transvenous obliteration (RTO) for the prevention of variceal rebleeding in cirrhotic patients with portal vein thrombosis (PVT). Consecutive cirrhotic patients with PVT who underwent RTO for the prevention of variceal rebleeding between January 2002 and June 2019 were included in this multicenter retrospective study. The primary outcome measure was rebleeding. The secondary outcome measures were survival, other complications of portal hypertension, liver function, and PVT. Forty-five patients (mean age, 66.0 ± 10.6years; mean Model for End-Stage Liver Disease (MELD) score, 13.9 ± 5.5) were included. The 1-year actuarial probability of remaining free of rebleeding was 92.8 ± 4.0%. The 6-week, 1-year, and 3-year actuarial probabilities of survival were 79.8 ± 6.0%, 48.8 ± 7.7%, and 46.1 ± 7.9%, respectively. MELD score (hazard ratio (HR), 1.09 (95% confidence interval (CI), 1.01-1.17); p = .013) and ascites (HR, 2.84 (95% CI, 1.24-6.55); p = .014) were identified as significant predictors of survival. The 1-year actuarial probabilities of remaining free of new or worsening ascites and esophageal varices were 81.2 ± 8.7% and 89.2 ± 6.0%, respectively. No patients had overt hepatic encephalopathy during follow-up. MELD score significantly increased by a mean of 3.8 (95% CI, 1.7-6.0) at 3months (p = .001). PVT had improved in 32.0%, worsened in 12.0%, and remained unchanged in 56.0% of patients at 3months. RTO may be effective for the prevention of variceal rebleeding in cirrhotic patients with PVT. • Retrograde transvenous obliteration may prevent variceal rebleeding in cirrhotic patients with portal vein thrombosis. • The risks of other complications of portal hypertension may not be high after retrograde transvenous obliteration in cirrhotic patients with portal vein thrombosis. • Portal vein thrombosis may improve in approximately one-third of cirrhotic patients within 3months after retrograde transvenous obliteration.

TIPS vs. NSBB Plus Endotherapy for the Prevention of Variceal Rebleeding in NSBB Non-responders of Primary Prophylaxis

TIPS vs. NSBB Plus Endotherapy for the Prevention of Variceal Rebleeding in NSBB Non-responders of Primary Prophylaxis

Selective versus non-selective shunts for the prevention of variceal rebleeding

Selective versus non-selective shunts for the prevention of variceal rebleeding

Prevention and management of gastroesophageal varices

Bleeding from gastroesophageal varices is a serious complication in patients with liver cirrhosis and portal hypertension. Although there has been significance improvement in the prognosis of variceal bleeding with advancement in diagnostic and therapeutic modalities for its management, mortality rate still remains high. Therefore, appropriate prevention and rapid, effective management of bleeding from gastroesophageal varices is very important. Recently, various studies about management of gastoesophageal varices, including prevention of development and aggravation of varices, prevention of first variceal bleeding, management of acute variceal bleeding, and prevention of variceal rebleeding, have been published. The present article reviews published articles and practice guidelines to present the most optimal management of patients with gastroesophageal varices.

Multicentre randomised controlled study comparing carvedilol with variceal band ligation in the prevention of variceal rebleeding

Rebleeding after an initial oesophageal variceal haemorrhage remains a significant problem despite therapy with band ligation, non-selective β-blockers or a combination of these. Carvedilol is a vasodilating non-selective β-blocker with alpha-1 receptor and calcium channel antagonism. A recent study has suggested it is effective in the prevention of a first variceal bleed. Our aim was to compare oral carvedilol with variceal band ligation (VBL) in the prevention of rebleeding following a first variceal bleed. Patients who were stable 5 days after presentation with a first oesophageal variceal haemorrhage and had not been taking β-blockers were randomised to oral carvedilol or VBL. Patients were followed-up after one week, monthly, then every 3 months. The primary end point was variceal rebleeding on intention-to-treat analysis. 64 patients were randomised, 33 to carvedilol and 31 to VBL. 58 (90.6%) patients had alcohol related liver disease. Age and Child-Pugh score were similar in both groups at baseline. Median follow-up was 26.3 (interquartile range [IQR] 10.2-46.6)months. Compliance was 68% and 65% for carvedilol and VBL respectively (p=0.993) and serious adverse events between the two groups were similar (p=0.968). Variceal rebleeding occurred during follow-up in 12 (36.4%) and 11 (35.5%) patients in the carvedilol and VBL groups, respectively (p=0.857), with 9 (27.3%) and 16 (51.6%) deaths in each group, respectively (p=0.110). Carvedilol is not superior to VBL in the prevention of variceal rebleeding. The trend to a survival benefit for patients taking this drug compared with those undergoing banding requires further exploration.

Prevention of Variceal Rebleeding According to the Dose of Propranolol

Esophageal variceal bleeding is a common complication of liver cirrhosis. Non-selective beta blockers (NSBB) have been established in numerous studies as one of the medical treatment for cirrhosis, especially in the primary and secondary prevention of variceal bleeding. The dose of NSBB is adjusted for a reduction in the resting heart rate by 25%, to 55 beat/min, or until the occurrence of adverse effect. The mean adjusted dose of propranolol in Korean study is 160 mg/day. Nevertheless, low dose propranolol is frequently used in real clinical field. A study by Kwon et al. showed that effect of propranolol in the prevention for esophageal rebleeding was superior in maximally-tolerable dose group of propranolol than low dose group. In this editorial, we have reviewed the studies of prevention for variceal rebleeding focusing on the dose of propranolol. (Korean J Med 2014;86:30-32)

OC-003 Multicentre Randomised Controlled Study Comparing Carvedilol with Endoscopic Band Ligation in the Prevention of Variceal Rebleeding

Introduction Rebleeding after an initial oesophageal variceal haemorrhage remains a significant problem despite therapy with band ligation ± non-selective s-blockers. Carvedilol is a vasodilating non-selective s-blocker with alpha-1 receptor and calcium channel antagonism. It has a greater portal hypotensive effect than propranolol and has been shown to be effective in the prevention of a first variceal bleed. Our aim was to compare oral carvedilol with band ligation in the prevention of rebleeding following a first variceal bleed. Methods Patients who were stable 5 days after presentation with a first variceal haemorrhage and had not been taking (or had contraindications to) s-blockers, were randomised to oral carvedilol (6.25 mg daily then 12.5 mg daily after one week if tolerated) or a band ligation programme. Patients were followed up at clinic after one week, monthly, then 3-monthly. The primary end-point was variceal rebleeding, on intention-to-treat analysis. Results 63 patients were randomised, 32 to carvedilol and 31 to banding. Fifty-six (89%) patients had alcohol related liver disease. There was no difference in baseline mean age (51 yrs ± 10.9 and 50 yrs ± 13.0) or median Childs Pugh score (9, IQR 6–11 and 9, IQR 8–11) for patients randomised to carvedilol or banding respectively. Mean follow-up was 29 months. Compliance was 72% and 90% for carvedilol and banding respectively (p = 0.14) and there was no difference in the number of serious adverse events between the two groups. Variceal rebleeding occurred during follow-up in 12 (37.5%) and 9 (29.0%) patients in the carvedilol and banding groups respectively (p = 0.72), with mortality 25.0% and 51.6% respectively (p = 0.058). The differences in outcome the between groups were similar using per protocol analysis. This interim analysis indicates that to show a significant difference in rebleeding, 482 patients would be required in each group. Conclusion Carvedilol is not clearly superior to band ligation in the prevention of variceal rebleeding. However there appears to be a survival benefit for patients taking this drug compared with those undergoing banding, which requires further exploration. Disclosure of Interest None Declared

Prevention of variceal rebleeding by TIPS combined with embolization of gastric coronary veins: a clinical controlled study

To prospectively compare the rates of gastroesophageal variceal rebleeding in patients underwent TIPS alone and TIPS combined with embolization of gastric coronary veins. According to the bleeding state within one week before the shunt placement, 122 patients with hepatic cirrhosis indicated for the secondary prevention of gastroesophageal variceal rebleeding were allocated to the shunt group (n = 44, treated with TIPS alone) and the shunt plus embolization group (n = 78, treated with TIPS combined with embolization of gastric coronary veins). All the patients were followed up for 1 year, and the 1-year cumulative rates of rebleeding, shunt patency and mortality were compared. The basic characteristics of patients in the two groups were comparable (P is more than 0.05). The 1-year cumulative re-bleeding rates were 41.5% in the shunt group and 19.5% in the shunt combined with embolization group (x2 = 6.320, P = 0.012). The differences of 1-year cumulative rates of shunt patency and mortality between the two groups were not significant (P is more than 0.05). TIPS combined with embolization of gastric coronary veins could reduce significantly the rate of rebleeding in 1 year after the shunt placement as compared with TIPS alone.

Propranolol and endoscopic sclerotherapy in the prevention of variceal rebleeding in patients with cirrhosis: a meta-analysis

Propranolol and endoscopic sclerotherapy in the prevention of variceal rebleeding in patients with cirrhosis: a meta-analysis

Response to β-Blocker Therapy and Risk for Variceal Bleeding

Previous studies in prevention of variceal rebleeding have demonstrated that a drop in hepatic venous pressure gradient (HVPG) below 12 mm Hg or a

A randomized, controlled trial of banding ligation plus drug therapy versus drug therapy alone in the prevention of esophageal variceal rebleeding

Both medications with beta-blockers and isosorbide-5-mononitrate and endoscopic variceal ligation have been proven plausible in the prevention of variceal rebleeding. However, the relative efficacy and safety of the combined treatment for preventing rebleeding remains unresolved. Patients with history of esophageal variceal bleeding were enrolled. Emergency ligation was performed in patients with acute variceal bleeding. After hemodynamic stability, eligible patients were randomized to either the Medication group, using nadolol plus isorsorbide-5-mononitrate, or the Combined group, receiving banding ligation in addition to medications. Patients in the two groups with rebleeding from esophageal varices were treated with band ligation. The end points were rebleeding from varices or death. After a median follow up of 23 months, recurrent upper gastrointestinal bleeding developed in 51% in the Medication group and 38% in the Combined group (P = 0.21). Recurrent bleeding from esophageal varices occurred in 26 patients (43%) in the Medication group and in 16 patients (26%) in the Combined group (P = 0.07). Recurrent bleeding from gastroesophageal varices occurred in 48% of Medication group and 28% of Combined group (P = 0.05). The frequency of adverse effects and mortality rates were similar between both groups (P = 0.28). Combined ligation with medications was marginally more effective than medication alone in the prevention of gastroesophageal variceal rebleeding with similar adverse effects and mortality.

AASLD practice guidelines the role of transjugular intrahepatic portosystemic shunt (TIPS) in the management of portal hypertension update 2009

The 2009 update of the American Association for the Study of Liver Diseases (AASLD) Practice Guideline “The Role of Transjugular Intrahepatic Portosystemic Shunt (TIPS) in the Management of Portal Hypertension” is now posted online at www.aasld.org. This is the first update of the original guideline published in 2005.1 DSRS, distal splenorenal shunt; TIPS, transjugular intrahepatic portosystemic shunt. The key changes in the 2009 guidelines are new recommendations on the use of covered versus bare stents in the creation of the TIPS. Use of expanded polytetrafluoroethylene (ePTFE)-covered stents is now preferred. The lower risk of shunt dysfunction and perhaps improved outcomes using covered as opposed to bare stents are the basis for this recommendation.2, 3 Creation of a TIPS increases the risk of hepatic encephalopathy but the prophylactic use of nonabsorbable disaccharides or antibiotics does not appear to reduce this risk and is not recommended.4 The value of TIPS versus a surgical shunt in the prevention of variceal rebleeding in patients who have failed medical therapy has been clarified by the publication of a controlled trial comparing TIPS to distal splenorenal shunt (DSRS).5 Both were effective in preventing rebleeding (rebleeding incidence in 5.5% of DSRS versus 10.5% of TIPS; not significant) with no difference in encephalopathy or survival. The patients in whom TIPS was performed required significantly more interventions to maintain patency because of the use of bare stents. A cost analysis showed TIPS to be slightly more cost effective than DSRS at year 5,6 and these two approaches are now considered to be of equal efficacy in the prevention of variceal rebleeding. The other significant change to the guidelines is how TIPS should be used in the management of patients with Budd-Chiari syndrome. A large (221 patients) retrospective study was published in which patients who failed to improve with use of anticoagulation had a TIPS created (133 patients). One-year and 10-year transplant-free survival was 88% and 69%, respectively, which is better than predicted.7 TIPS patency was best in those who received a covered stent. The recommendation now is for creation of a TIPS in those who fail to improve with anticoagulation.

Improved survival in patients receiving medical therapy as compared with banding ligation for the prevention of esophageal variceal rebleeding

Both medical therapy and endoscopic variceal ligation (EVL) have proven to be comparable in the prevention of variceal rebleeding. However, the long-term results are still lacking. Our previous study enrolled 121 patients with history of esophageal variceal bleeding and randomized to receive EVL (EVL group, 60 patients) or drug therapy, nadolol plus isosorbide-5-mononitrate (N+I) (N+I group, 61 patients) to prevent variceal rebleeding. The EVL group received ligation regularly until variceal obliteration. The N+I group received N+I during the study period. Patients were followed for up to 8 years. After a median follow-up of 82 months, recurrent upper gastrointestinal bleeding developed in 28 patients (47%) in the EVL group and 49 patients (80%) in the N+I group (P = 0.001). Recurrent bleeding from esophageal varices occurred in 18 patients (30%) in the EVL group and 39 patients (64%) in the N+I group. The actuarial probability of rebleeding from esophageal varices was lower in the EVL group (P = 0.001). A total of 42 patients of the EVL group and 30 patients of the N+I group died (P = 0.013). The multivariate Cox analysis indicated that age, serum albumin, presence of encephalopathy, and treatment were the factors predictive of mortality. Our long-term follow-up study showed that combination of N+I therapy was inferior to banding ligation in the reduction of variceal rebleeding, but with enhanced survival.

Prevention of Recurrent Esophageal Variceal Hemorrhage

Variceal rebleeding is a very frequent and severe complication in cirrhotic patients; therefore, its prevention should be mandatory. Lately several studies demonstrated that the rate of rebleeding was decreased by 40% and overall survival is improved by 20% with beta-blockers. However, this treatment presents some problems, such as the number of nonresponders and contraindications for its use. Recent trials found that the combination of beta-blockers with mononitrate of isosorbide to be superior to beta-blockade alone. Furthermore, endoscopic band ligation also shown to decrease the frequency of rebleeding, complications, and death compared with sclerotherapy and should be the preferred endoscopic treatment. In addition, the comparison between combined pharmacologic treatment with endoscopic treatment present similar rebleeding and mortality rates. More recently, the addition of nadolol to endoscopic band ligation increased the efficacy of endoscopy alone in the prevention of variceal rebleeding. These studies suggest that banding plus drugs could be the treatment of choice for the prophylaxis of rebleeding. When these treatments fail, the recommendation is to use transjugular intrahepatic portosystemic shunt (TIPS) or surgical shunts. Both treatments are effective in preventing rebleeding; however, they are associated with a greater risk of encephalopathy. The comparison of portacaval shunts with TIPS demonstrated that TIPS patients presented higher rebleeding, treatment failure, and transplantation. Another randomized controlled trial comparing distal splenorenal shunt with TIPS shows that variceal rebleeding was similar in both groups without differences in encephalopathy and mortality. The only difference observed was the higher rate of reintervention observed in the TIPS group to maintain his patency.

Cost of preventing variceal rebleeding with transjugular intrahepatic portal systemic shunt and distal splenorenal shunt

We examined the cost and cost effectiveness of distal splenorenal shunt (DSRS) and transjugular intrahepatic portosystemic shunt (TIPS) in the prevention of variceal rebleeding. Patients participated in a randomized controlled trial comparing DSRS to TIPS. Quality of life (QOL) was measured using SF-36 preceding randomization and yearly thereafter. Cost utility analysis was performed using TreeAge DATA. Costs for both in- and out-patient events and interventions were obtained for each patient. Costs using coated stents were estimated using different rates of stenosis. Incremental cost effectiveness ratios (ICERs) were determined at 1, 3 and 5 years. The average yearly costs of managing patients after TIPS and DSRS over 5 years were similar, $16,363 and $13,492, respectively. Cost of TIPS for surviving patients exceeded the cost of DSRS at years 3 and 5 but not significantly. ICERs per life saved favored TIPS at year 5 ($61,000). If coated rather than bare stents were used the cost effectiveness of TIPS increased slightly. TIPS is as effective as DSRS in preventing variceal rebleeding and may be more cost effective. TIPS, in all aspects, is equal to DSRS in the prevention of variceal rebleeding in patients who are medical failures.

Comparative study between nadolol and 5‐isosorbide mononitrate vs. endoscopic band ligation plus sclerotherapy in the prevention of variceal rebleeding in cirrhotic patients: a randomized controlled trial

After variceal bleeding, cirrhotic patients should receive secondary prophylaxis. To compare nadolol plus 5-isosorbide mononitrate (5-ISMN) with endoscopic band ligation. The end points were rebleeding, treatment failure and death. One hundred and nine cirrhotic patients with a recent variceal bleeding were randomized: nadolol plus 5-ISMN in 57 patients and endoscopic band ligation in 52 patients. The mean follow-up was 17 and 19 months in nadolol plus 5-ISMN and endoscopic band ligation groups, respectively. No differences were observed between groups in upper rebleeding (47% vs. 46%), variceal rebleeding (40% vs. 36%), failure (32% vs. 22%), major complications (7% vs. 13.5%) and death (19% vs. 20%), respectively. The actuarial probability of remaining free of rebleeding, failure and deaths were similar in both groups. Time to rebleeding shows that endoscopic band ligation patients had an early rebleed, with a median of 0.5 month (95% CI: 0.0-4.2) compared with patients from nadolol plus 5-ISMN, 7.6 months (95% CI: 2.9-12.3, P < 0.013). Multivariate analysis indicated that outcome-specific predictive factor(s) for rebleeding was Child A vs. B + C (P < 0.01); for failure was Child A vs. B + C (P < 0.02); and for death ascites (P < 0.01) and rebleeding (P < 0.02). This trial suggests no superiority of endoscopic band ligation over nadolol plus 5-ISMN mononitrate for the prevention of rebleeding in cirrhotic patients.

Transjugular Intrahepatic Portosystemic Shunts: Adjunctive Embolotherapy of Gastroesophageal Collateral Vessels in the Prevention of Variceal Rebleeding

Transjugular Intrahepatic Portosystemic Shunts: Adjunctive Embolotherapy of Gastroesophageal Collateral Vessels in the Prevention of Variceal Rebleeding

Natural history of a randomized trial comparing distal spleno-renal shunt with endoscopic sclerotherapy in the prevention of variceal rebleeding: A lesson from the past

To compare endoscopic sclerotherapy (ES) with distal splenorenal shunt (DSRS) in the prevention of recurrent variceal bleeding in cirrhotic patients during a long-term follow-up period. In 1984 we started a prospective, controlled study of patients with liver cirrhosis. Long-term follow-up presents a natural history of liver cirrhosis complicated by advanced portal hypertension. In this study the effects of 2 types of treatment, DSRS or ES, were evaluated. The study population included 80 patients with cirrhosis and portal hypertension referred to our department from October 1984 to March 1991. These patients were drawn from a pool of 282 patients who underwent either elective surgery or ES during the same period of time. Patients were assigned to one of the 2 groups according to a random number table: 40 to DSRS and 40 to ES using polidocanol. During the postoperative period, no DSRS patient died, while one ES patient died of uncontrolled hemorrhage. One DSRS patient had mild recurrent variceal hemorrhage despite an angiographically patent DSRS and another patient suffered duodenal ulcer rebleeding. Eight ES patients suffered at least one episode of gastrointestinal bleeding: 4 from varices and 4 from esophageal ulcerations. Eight ES patients developed transitory dysphagia. Long-term follow-up was completed in all patients except for 5 cases (2 DSRS and 3 ES patients). Five-year survival rates for shunt (73%) and ES (56%) groups were statistically different: in this follow-up period and in subsequent follow-ups this difference decreased and ceased to be of statistical relevance. The primary cause of death became hepatocellular carcinoma (HCC). Four DSRS patients rebled due to duodenal ulcer, while eleven ES patients had recurrent bleeding from esophago-gastric sources (seven from varices, three from hypertensive gastropathy, one from esophageal ulcerations) and two from unknown sources. Nine DSRS and 2 ES patients developed a chronic encephalopathy; 13 DSRS and 5 ES patients suffered at least one episode of acute encephalopathy. Five ES patients had esophageal stenoses, which were successfully dilated. In a subgroup of patients with good liver function, DSRS with a correct portal-azygos disconnection more effectively prevents variceal rebleeding than ES. However, this positive effect did not influence the long-term survival because other factors (e.g. HCC) were more important in deciding the fate of the cirrhotic patients with portal hypertension.