Prophylaxis Of Esophageal Variceal Bleeding Research Articles

Continuing Medical Education Questions: February 2024.

Article Title: A Randomized Controlled Trial of Propranolol Use During Ligation Program for Secondary Prophylaxis of Esophageal Variceal Bleeding.

A Randomized Controlled Trial of Propranolol Use During Ligation Program for Secondary Prophylaxis of Esophageal Variceal Bleeding.

Endoscopic variceal ligation (EVL) plus nonselective β-blockers (NSBB) is the standard of care for secondary prophylaxis of esophageal variceal bleeding (EVB). This trial aimed to compare the rebleeding rates between EVL plus NSBB till eradication of esophageal varices (EEV) and EVL plus long-term NSBB. After control of acute EVB, patients with cirrhosis were randomized into 2 groups, with group A patients receiving EVL plus propranolol till EEV, while group B patients received standard of care with continuation of propranolol. Recurrent varices were ligated at follow-up endoscopy in both groups. The median follow-up period was 23.0 months in group A (n = 106) and 23.6 months in group B (n = 106). Twelve patients (11.3%) in group A and 11 (10.4%) in group B had recurrent EVB. The difference in rebleeding rates and the 95% confidence interval (CI) was 0.9% (-7.5% to 9.3%). The upper 95% CI bound of the difference was within the margin of 13.2%, and the noninferiority of group A to group B was established. Thirty-eight patients (35.8%) in group A and 40 (37.7%) in group B had further decompensation, with the difference (95% CI) of -1.9% (-14.9% to 11.1%). Twenty-four patients (22.6%) in group A and 26 (24.5%) in group B expired, with the difference (95% CI) in mortality rates of -1.9% (-13.3% to 9.5%). EVL plus propranolol till EEV was noninferior to EVL plus continuing propranolol in secondary prophylaxis of EVB, but the impact on further decompensation and transplantation-free survival deserved further investigation.

Nonselective beta-blockers in primary prophylaxis of esophageal variceal bleeding in patients with ascites waitlisted for liver transplantation

Objective: to determine the efficacy of non-selective beta-blockers (NSBBs) in the primary prevention of bleeding esophageal varices and to assess their impact on the survival of patients with ascites enrolled in the liver transplant waiting list (LTWL).Materials and methods. We carried out a retrospective comparative study of cirrhotic patients with severe ascites and esophageal varices without bleeding before enrollment in the LTWL. Primary prophylaxis of variceal bleeding included the use of NSBBs (n = 97, group 1). These drugs were not used in the other patients (n = 91, group 2).Results. There were no significant differences between the groups in terms of clinical, laboratory and demographic parameters, MELD scores and Child-Turcotte-Pugh (CTP) classes for cirrhosis. Patient groups included in the study had no significant differences with respect to incidence of medium- and large-sized varices and incidence of severe ascites. Bleeding incidence was significantly lower in the NSBBs group than in the non-NSBBs group (52.6% and 95.6%, respectively, p = 0.0001).Conclusion. NSBBs constitute an efficacious therapy in primary prophylaxis of esophageal variceal bleeding, thereby saving life and preventing delisting of patients with ascites from the LTWL.

Metástasis de origen pulmonar de localización inusual

Esophageal varices are present in majority of the patients with hepatic cirrhosis at the time of diagnosis, especially in those with advanced liver disease. Variceal size, red wale marks on varices, and advanced liver disease are risk factors for variceal hemorrhage. Esophageal variceal ligation (EVL) is a standard endoscopic procedure in the management of acute variceal bleeding and is beneficial in the primary and secondary prophylaxis of esophageal variceal bleeding. Multiband devices are commonly used for EVL. Various endoscopic techniques, common clinical scenarios, and procedure-related complications in EVL are described in the video manuscript provided. This article is part of an expert video encyclopedia.

S1217 Secondary and Tertiary Prophylaxis of Esophageal Variceal Bleeding: Can We Be Doing Better?

S1217 Secondary and Tertiary Prophylaxis of Esophageal Variceal Bleeding: Can We Be Doing Better?

Beta-blockers versus placebo or no intervention for primary prophylaxis of oesophageal variceal bleeding in children with chronic liver disease or portal vein thrombosis.

Portal hypertension commonly accompanies advanced liver disease and often gives rise to life-threatening complications, including haemorrhage from oesophageal and gastrointestinal varices. Variceal haemorrhage commonly occurs in children with chronic liver disease or portal vein thrombosis. Therefore, prevention is important. Band ligation, beta-blockers, and sclerotherapy have been proposed as alternatives for primary prophylaxis of oesophageal variceal bleeding in children. However, primary prophylaxis is not the current standard of care in paediatric patients because it is unknown whether those treatments are of benefit or harm when used for primary prophylaxis in children and adolescents. To determine the benefits and harms of beta-blockers compared with placebo or no intervention for primary prophylaxis of oesophageal variceal bleeding in children with chronic liver disease or portal vein thrombosis. We searched the Cochrane Hepato-Biliary Group Controlled Trials Register, CENTRAL, PubMed, Embase, LILACS, and Science Citation Index Expanded (April 2020). We screened the reference lists of the retrieved publications and manually searched the main paediatric gastroenterology and hepatology conference (NASPGHAN and ESPGHAN) abstract books from 2008 to December 2019. We searched clinicaltrials.gov, the United States Food and Drug Administration (FDA), the European Medicines Agency (EMA), and the World Health Organization (WHO) for ongoing clinical trials. We imposed no language or document type restrictions on our search. We planned to include randomised clinical trials, irrespective of blinding, language, or publication status to assess benefits and harms. We included observational studies, retrieved with the searches for randomised clinical trials, for a narrative report of harm. We planned to summarise data from randomised clinical trials by standard Cochrane methodologies. We planned to asses risk of bias and use GRADE to assess the certainty of evidence. Our primary outcomes were all-cause mortality, serious adverse events and liver-related morbidity, and health-related quality of life. Our secondary outcomes were oesophageal variceal bleeding and adverse events not considered serious. We planned to use intention-to-treat principle. We planned to analyse data with RevMan Analysis. We found no randomised clinical trials that assessed beta-blockers compared with sham or no intervention for primary prophylaxis of oesophageal variceal bleeding in children with chronic liver disease or portal vein thrombosis. We found four observational studies that reported on harms. As a systematic search for observational studies was not planned, we only listed the reported harms in a table. Randomised clinical trials assessing the benefits or harms of beta-blockers versus placebo or no intervention for primary prophylaxis of oesophageal variceal bleeding in children with chronic liver disease or portal vein thrombosis are lacking. Therefore, trials with adequate power and proper design, assessing the benefits and harms of beta-blockers versus placebo on patient-relevant clinical outcomes, such as mortality, quality of life, failure to control variceal bleeding, and adverse events are needed. Unless such trials are conducted and the results become published, we cannot make any conclusions regarding the benefits or harms of the two interventions.

Band ligation versus sham or no intervention for primary prophylaxis of oesophageal variceal bleeding in children and adolescents with chronic liver disease or portal vein thrombosis.

Band ligation versus sham or no intervention for primary prophylaxis of oesophageal variceal bleeding in children and adolescents with chronic liver disease or portal vein thrombosis.

Band ligation versus sclerotherapy for primary prophylaxis of oesophageal variceal bleeding in children with chronic liver disease or portal vein thrombosis.

Portal hypertension commonly accompanies advanced liver disease and often gives rise to life-threatening complications, including haemorrhage from oesophageal and gastrointestinal varices. Variceal haemorrhage commonly occurs in children with chronic liver disease or portal vein obstruction. Prevention is therefore important. In adults, numerous randomised clinical trials have demonstrated benefits of non-selective beta-blockers and endoscopic variceal ligation as primary prevention in decreasing the risk of variceal haemorrhage. In children, band ligation, beta-blockers, and sclerotherapy have been proposed as alternatives for primary prophylaxis of oesophageal variceal bleeding. However, primary prophylaxis is not the current standard of care in children because it is unknown whether those treatments are of benefit or cause harm when used for primary prophylaxis of oesophageal variceal bleeding in children and adolescents. To determine the benefits and harms of band ligation versus sclerotherapy for primary prophylaxis of oesophageal variceal bleeding in children and adolescents with chronic liver disease or portal vein thrombosis. We searched the Cochrane Hepato-Biliary Group Controlled Trials Register, CENTRAL, PubMed, Embase, LILACS, and Science Citation Index Expanded (27 April 2020). We scrutinised the reference lists of retrieved publications, and performed a manual search from the main paediatric gastroenterology and hepatology conferences (NASPGHAN and ESPGHAN) abstract books from 2008 to 2019. We searched ClinicalTrials.gov, FDA, EMA, and WHO for ongoing clinical trials. There were no language or document type restrictions. We planned to include randomised clinical trials irrespective of blinding, language, or publication status for assessment of benefits and harms. If the search for randomised clinical trials retrieved quasi-randomised and observational studies, then we read them through to extract information on harms. We planned to summarise data from randomised clinical trials by standard Cochrane methodologies. We planned to assess risk of bias and use GRADE to assess the certainty of evidence per outcome. Our primary outcomes were all-cause mortality, serious adverse events and liver-related morbidity, and quality of life. Our secondary outcomes were oesophageal variceal bleeding and adverse events not considered serious. We planned to analyse data with intention-to-treat. We planned to use Review Manager 5 to analyse the data. We found no randomised clinical trials assessing band ligation versus sclerotherapy for primary prophylaxis of oesophageal variceal bleeding in children with chronic liver disease or portal vein thrombosis. Randomised clinical trials assessing the benefits or harms of band ligation versus sclerotherapy for primary prophylaxis of oesophageal variceal bleeding in children with chronic liver disease or portal vein thrombosis are lacking. Therefore, trials with adequate power and proper design, assessing the benefits and harms of band ligation versus sclerotherapy on patient-relevant clinical outcomes such as mortality, quality of life, failure to control variceal bleeding, and adverse events are needed. Unless such trials are conducted and the results become published, we cannot make any conclusions regarding the benefits or harms of these two interventions.

Primary prevention of bleeding from esophageal varices in patients with liver cirrhosis: An update and review of the literature.

All patients with liver cirrhosis and portal hypertension should be stratified by risk groups to individualize different therapeutic strategies to increase the effectiveness of treatment. In this regard, the development of primary prophylaxis of variceal bleeding and its management according to the severity of portal hypertension may be promising. This paper is to describe the modern principles of primary prophylaxis of esophageal variceal bleeding in patients with liver cirrhosis. The PubMed and EMbase databases, Web of Science, Google Scholar, and the Cochrane Database of Systematic Reviews were used to search for relevant publications from 1999 to 2019. The results suggested that depending on the severity of portal hypertension, patients with cirrhosis should be divided into those who need preprimary prophylaxis, which aims to prevent the formation of esophageal varices, and those who require measures that aim to prevent esophageal variceal bleeding. In subclinical portal hypertension, therapy should be etiological and pathogenetic. Cirrhosis with clinically significant portal hypertension should receive nonselective β-blockers if they have small esophageal varices and risk factors for variceal bleeding. Nonselective β-blockers are the first-line drugs for the primary prevention of bleeding from medium to large-sized esophageal varices. Endoscopic band ligation is indicated for the patients who are intolerant to nonselective β-blockers or in the case of contraindications to pharmacological therapy. In summary, the stratification of cirrhotic patients by the severity of portal hypertension and an individual approach to the choice of treatment may increase the effectiveness of therapy as well as improve survival rate of these patients.

POTENTIAL PREDICTORS AND OUTCOMES OF BLEEDING EVENTS AFTER ESOPHAGEAL VARICEAL LIGATION

SESSION TITLE: Critical Care Posters SESSION TYPE: Original Investigation Posters PRESENTED ON: October 18-21, 2020 PURPOSE: Esophageal Variceal Ligation (EVL) has been used for primary prophylaxis, acute bleeding episodes, and secondary prophylaxis of esophageal variceal hemorrhage. The most common complications of EVL are dysphagia, chest pain, intra-operative bleeding, and post-procedural bleeding from ulcer formation. The aim of our study is to identify risk factors for a bleeding event and compare outcomes in those patients who bled and those who did not bleed after EVL. METHODS: This is a retrospective cohort study. The data was gathered from the EPIC electronic medical record using Clinical Looking Glass (Emerging Health Information Technology, Yonkers, New York). We analyzed 480 EVL procedures performed in patients with cirrhosis (alcoholic, hepatitis C, hepatitis B, autoimmune, and non-alcoholic steato-hepatitis) between 2014 to 2019. RESULTS: Average age was similar between the groups that bled and the group that did not bleed (59.4 vs 59.7, p=0.92). Intubation rates were higher in the group that bled versus the group that did not bleed (42% v 6%, p<0.01). Vasopressors were more likely to be required in the group that bled versus the group that did not bleed (26% v 3%, p<0.01). The Model for End Stage Liver Disease, Sodium (MELD-Na) scores were significantly higher in the group that bled compared to the group that did not bleed (9.87 v 6.24, p<0.01). APRI (AST to Platelet Ratio Index) scores were significantly higher in the group that bled compared to the group that did not bleed (4.82 v 2.01, p=0.04). CONCLUSIONS: APRI score and MELD-Na scores can help predict bleeding events. Bleeding after EVL is a serious event associated with a higher intubation rate and greater need for vasopressors. CLINICAL IMPLICATIONS: Critical Care physicians can use APRI and MELD-Na scores to anticipate bleeding events after EVL and be better prepared for next steps in management. DISCLOSURES: No relevant relationships by Lewis Eisen, source=Web Response No relevant relationships by Galina Glazman-Kuczaj, source=Web Response No relevant relationships by Ariel Karten, source=Web Response No relevant relationships by Christa McPhee, source=Web Response No relevant relationships by Ariel Shiloh, source=Web Response

Comparison of Therapies for Secondary Prophylaxis of Esophageal Variceal Bleeding in Cirrhosis: A Network Meta-analysis of Randomized Controlled Trials

PurposeThe decision regarding the optimal secondary prophylactic treatment for esophageal variceal bleeding (EVB) in hepatic cirrhosis is controversial. A network meta-analysis was conducted to assess the benefits of various treatments for the secondary prophylaxis of EVB in patients with cirrhosis. MethodsA thorough examination of databases, including EMBASE, PubMed, and Cochrane Database of Controlled Trials, was conducted to identify relevant randomized controlled trials up to December 2019. Key primary outcomes included mortality and rebleeding. Within the identified databases, a network meta-analysis was performed. Results were expressed by using a 95% credible interval (CrI) and odds ratios (ORs). The quality of results was assessed by using the Grading of Recommendations, Assessment, Development and Evaluation approach. FindingsForty-eight trials with 4415 participants with cirrhosis and portal hypertension who had a history of recent variceal bleeding were included. Carvedilol ranked first (surface under the cumulative ranking curve [SUCRA], 87.4%) in overall survival, and some advantage was suggested; however, the findings were not statistically significant, compared with endoscopic variceal ligation + nonselective beta-blockers (NSBB) (OR, 0.59; CrI, 0.28, 1.3), NSBB + isosorbide mononitrate (OR, 0.67; CrI, 0.33, 1.4), and transjugular intrahepatic portosystemic shunt (TIPS) (OR, 0.52; CrI, 0.24, 1.1). NSBB + isosorbide mononitrate (SUCRA, 63.9%) ranked higher than NSBB + endoscopic variceal ligation (SUCRA, 49.6%) in reducing mortality. TIPS (SUCRA, 98.8%) ranked higher than other treatments in reducing rebleeding but did not confer any survival benefit. ImplicationsTIPS ranks first in preventing rebleeding of secondary prophylaxis of EVB and carvedilol shows outstanding efficacy in improving survival. International Prospective Register of Systematic Reviews: identifier CRD42019131814.

Sclerotherapy versus sham or no intervention for primary prophylaxis of oesophageal variceal bleeding in children with chronic liver disease or portal vein thrombosis.

Portal hypertension commonly accompanies advanced liver disease and often gives rise to life-threatening complications, including bleeding (haemorrhage) from oesophageal and gastrointestinal varices. Variceal bleeding commonly occurs in children with chronic liver disease or portal vein obstruction. Therefore, prevention is important. Primary prophylaxis of variceal bleeding in adults is the established standard of care because of the results of numerous randomised clinical trials demonstrating the efficacy of non-selective beta-blockers or endoscopic variceal ligation in decreasing the incidence of variceal bleeding. In children, band ligation, beta-blockers, and sclerotherapy have been proposed as alternatives for primary prophylaxis of oesophageal variceal bleeding. However, it is unknown whether those treatments are of benefit or harm when used for primary prophylaxis in children. To assess the benefits and harms of sclerotherapy compared with sham or no intervention for primary prophylaxis of oesophageal variceal bleeding in children with chronic liver disease or portal vein thrombosis. We searched The Cochrane Hepato-Biliary Group Controlled Trials Register, CENTRAL, PubMed, Embase Elsevier, and two other registers in February 2019. We scrutinised the reference lists of the retrieved publications, and performed a manual search of the main paediatric gastroenterology and hepatology conference (NASPGHAN and ESPGHAN) abstracts from January 2008 to December 2018. We searched four registries for ongoing clinical trials. There were no language or document type restrictions. We included randomised clinical trials irrespective of blinding, language, or publication status assessing sclerotherapy versus sham or no intervention for primary prophylaxis of oesophageal variceal bleeding in children with chronic liver disease or portal vein thrombosis. We used standard Cochrane methodology to perform this systematic review. We used the intention-to-treat principle to analyse outcome data, and GRADE to assess the certainty of evidence per outcome. We found only one randomised clinical trial that fulfilled our inclusion criteria. The trial was at high risk of bias. The trial included 108 Brazilian children with median age of 4.3 years (range 11 months to 13 years). Fifty-six children were randomised to prophylactic sclerotherapy (ethanolamine oleate 2%) and 52 children to no intervention (control). Children were followed up for a median of 4.5 years. Eight children (six from the sclerotherapy group versus two from the control group) dropped out before the end of the trial. The follow-up was from 18 months to eight years. Mortality was 16% (9/56 children) in the sclerotherapy group versus 15% (8/52 children) in the control group (risk ration (RR) 1.04, 95% confidence interval (CI) 0.44 to 2.50; very low-certainty evidence). Upper gastrointestinal bleeding occurred in 21% (12/56) of the children in the sclerotherapy group versus 46% (24/52) in the control group (RR 0.46, 95% CI 0.26 to 0.83; very low-certainty evidence). There were more children with congestive hypertensive gastropathy in the sclerotherapy group than in the control group (14% (8/56) versus 6% (3/52); RR 2.48, 95% CI 0.69 to 8.84; very low-certainty evidence). The incidence of gastric varices was similar between the sclerotherapy group and the control group (11% (6/56) versus 10% (5/52); RR 1.11, 95% CI 0.36 to 3.43; very low-certainty evidence). The incidence of bleeding from gastric varices was higher in the sclerotherapy group than in the control group (4% (3/56) versus 0% (0/52); RR 6.51, 95% CI 0.34 to 123.06; very low-certainty evidence). The study did not assess health-related quality of life. Oesophageal variceal bleeding occurred in 5% (3/56) of the children in the sclerotherapy group versus 40% (21/52) of the children in the control group (RR 0.13, 95% CI 0.04 to 0.42; very low-certainty evidence). The most prevalent complications (defined as non-serious) were pain and fever after the procedure, which promptly resolved with analgesics. However, numerical data on the frequency of these adverse events and their occurrences in the two groups were lacking. No funding information was provided. We found no ongoing trials. The evidence, obtained from one randomised clinical trial at high risk of bias, is very uncertain on whether sclerotherapy has an influence on mortality and if it may decrease first upper gastrointestinal or oesophageal variceal bleeding in children. The evidence is very uncertain on whether sclerotherapy has an influence on congestive hypertensive gastropathy, incidence on gastric varices, and incidence of bleeding from gastric varices. Health-related quality of life was not measured. There were no serious events caused by sclerotherapy, and analysis of non-serious adverse events could not be performed due to lack of numerical data. The GRADE assessment of each outcome showed a very low-certainty evidence. The results of the trial need to be interpreted with caution. Larger randomised clinical trials, following the SPIRIT and CONSORT statements, assessing the benefits and harms of sclerotherapy compared with sham or no intervention for primary prophylaxis of oesophageal variceal bleeding in children with chronic liver disease or portal vein thrombosis are needed. The trials should include important clinical outcomes such as death, failure to control bleeding, and adverse events.

Sclerotherapy versus beta-blockers for primary prophylaxis of oesophageal variceal bleeding in children and adolescents with chronic liver disease or portal vein thrombosis.

Portal hypertension commonly accompanies advanced liver disease and often gives rise to life-threatening complications, including bleeding (haemorrhage) from oesophageal and gastrointestinal varices. Variceal bleeding commonly occurs in children with chronic liver disease or portal vein obstruction. Prevention is therefore important. Primary prophylaxis of variceal bleeding in adults is the established standard of care because of the results of numerous randomised clinical trials demonstrating the efficacy of non-selective beta-blockers or endoscopic variceal ligation in decreasing the incidence of variceal bleeding. However, sclerotherapy is the only endoscopic prophylactic option currently available in infants weighing less than 10 kg of bodyweight due to the size of the endoscopic ligator. To assess the benefits and harms of sclerotherapy versus any type of beta-blocker for primary prophylaxis of oesophageal variceal bleeding in children and adolescents with chronic liver disease or portal vein thrombosis. We searched The Cochrane Hepato-Biliary Group Controlled Trials Register, CENTRAL, PubMed, Embase Elsevier, LILACS (Bireme), and Science Citation Index Expanded (Web of Science) in February 2019. We scrutinised the reference lists of the retrieved publications and performed a manual search from the main paediatric gastroenterology and hepatology conferences (NASPGHAN and ESPGHAN) abstract books from January 2008 to December 2018. We searched ClinicalTrials.gov, FDA, EMA, and WHO, for ongoing clinical trials. There were no language or document type restrictions. We planned to include randomised clinical trials irrespective of blinding, language, or publication status, assessing sclerotherapy versus any type of beta-blocker for primary prophylaxis of oesophageal variceal bleeding in children and adolescents with chronic liver disease or portal vein thrombosis. We planned to include quasi-randomised and other observational studies retrieved with the searches for randomised clinical trials for report of harm. We planned to collect and summarise data from randomised clinical trials as described in our protocol, using standard Cochrane methodologies. We found no randomised clinical trials assessing sclerotherapy versus beta-blockers for primary prophylaxis of oesophageal variceal bleeding in children and adolescents with chronic liver disease or portal vein thrombosis. Randomised clinical trials assessing the benefits or harms of sclerotherapy versus beta-blockers for primary prophylaxis of oesophageal variceal bleeding in children and adolescents with chronic liver disease or portal vein thrombosis are lacking. Therefore, trials with adequate power and proper design, assessing the benefits and harms of sclerotherapy versus beta-blockers on patient-relevant clinical outcomes such as mortality, failure to control bleeding, and adverse events are needed. Unless such trials are conducted and the results become published, we cannot make any conclusions regarding the benefits or harms of the two interventions.

Band ligation versus beta-blockers for primary prophylaxis of oesophageal variceal bleeding in children with chronic liver disease or portal vein thrombosis.

Portal hypertension commonly accompanies advanced liver disease and often gives rise to life-threatening complications, including haemorrhage from oesophageal and gastrointestinal varices. Variceal haemorrhage commonly occurs in children with chronic liver disease or portal vein obstruction. Prevention is therefore important. Following numerous randomised clinical trials demonstrating efficacy of non-selective beta-blockers and endoscopic variceal ligation in decreasing the incidence of variceal haemorrhage, primary prophylaxis of variceal haemorrhage in adults has become the established standard of care. Hence, band ligation and beta-blockers have been proposed to be used as primary prophylaxis of oesophageal variceal bleeding in children. To determine the benefits and harms of band ligation compared with any type of beta-blocker for primary prophylaxis of oesophageal variceal bleeding in children with chronic liver disease or portal vein thrombosis. We searched The Cochrane Hepato-Biliary Group Controlled Trials Register (February 2019), CENTRAL (December 2018), PubMed (December 2018), Embase Ovid (December 2018), LILACS (Bireme; January 2019), and Science Citation Index Expanded (Web of Science; December 2018). We scrutinised the reference lists of the retrieved publications and performed a manual search from the main paediatric gastroenterology and hepatology conferences (NASPGHAN and ESPGHAN) abstract books from 2009 to 2018. We searched ClinicalTrials.gov for ongoing clinical trials. There were no language or document type restrictions. We planned to include randomised clinical trials irrespective of blinding, language, or publication status for assessment of benefits and harms. We planned to also include quasi-randomised and other observational studies retrieved with the searches for randomised clinical trials for report of harm. We planned to summarise data from randomised clinical trials using standard Cochrane methodologies. We found no randomised clinical trials assessing band ligation versus beta-blockers for primary prophylaxis of oesophageal variceal bleeding in children with chronic liver disease or portal vein thrombosis. Randomised clinical trials assessing the benefits or harms of band ligation versus beta-blockers for primary prophylaxis of oesophageal variceal bleeding in children with chronic liver disease or portal vein thrombosis are lacking. There is a need for well-designed, adequately powered randomised clinical trials to assess the benefits and harms of band ligation versus beta-blockers for primary prophylaxis of oesophageal variceal bleeding in children with chronic liver disease or portal vein thrombosis. Those randomised clinical trials should include patient-relevant clinical outcomes such as mortality, failure to control bleeding, and adverse events.

Nonselective beta-blockers and development of portal vein thrombosis in liver cirrhosis: a systematic review and meta-analysis.

Portal vein thrombosis (PVT), which is associated with reduced portalvein velocity, is considered to be an indicator for worse outcomes in liver cirrhosis. Nonselective beta-blockers (NSBBs), which are widely used for primary and secondary prophylaxis of esophageal variceal bleeding in liver cirrhosis, can significantly decrease the portal vein velocity. We proposed a hypothesis that the use of NSBBs might facilitate the development of PVT in cirrhotic patients. The PubMed, EMBASE, and Cochrane Library databases were searched. Major meeting abstracts and randomized-controlled trials regardingthe use of NSBBs in liver cirrhosis were also hand-searched. The number of patients who developed PVT in groups treated with or without NSBBs was pooled. Odds ratios (ORs) or risk ratios (RRs) with 95% confidence intervals (CIs) were calculated. Subgroup meta-analyses were performed according to the type of studies,region, and study quality. Meta-regression and sensitivity analyses were performed to explore the source of heterogeneity. Nine of the 6416 retrieved papers were finally included. Overall, meta-analysis demonstrated that NSBBs were significantly associated with the development of PVT (OR 4.62, 95% CI 2.50-8.53; p < 0.00001). The heterogeneity was statistically significant (I2 = 80%; p < 0.00001). Subgroup meta-analyses still demonstrated a significantly positive association of NSBBs with the development of PVT in cohort studies (RR 2.57, 95% CI 1.46-4.51; p = 0.001) and case-control studies (OR 8.17, 95% CI 2.46-27.06; p = 0.0006). Sensitivity analyses based on subgroups find the source of heterogeneity. Based on the systematic review and meta-analysis, we found that the use of NSBBs increased a 4.62-fold risk of PVT in cirrhotic patients.

Mo1531 – Early (Pre-Emptive) Tips Versus Conventional Treatment for Prophylaxis of Esophageal Variceal Bleeding: A Systematic Review and Meta-Analysis

Mo1531 – Early (Pre-Emptive) Tips Versus Conventional Treatment for Prophylaxis of Esophageal Variceal Bleeding: A Systematic Review and Meta-Analysis

Long-term outcome of endoscopic variceal band ligation of esophageal varices in patients with chronic liver disease.

There are scanty data on the long-term outcome of endoscopic variceal band ligation (EVL) for esophageal varices. Adult patients suffering from a chronic liver disease (CLD) undergoing EVL of esophageal varices of grade 2 and above between January 2006 andDecember 2015 were followed upfor the recurrence of varices, worsening of portal hypertensive gastropathy (PHG), rebleeding, and mortality. EVL was done as primary prophylaxis of bleeding in 72 and as secondary prophylaxis in 175 patients. All received propranolol after EVL if there was no contraindication. Two hundred and forty-seven CLD patients (mean age 51.83 ± 11.28years, 179 males) underwent 306 EVL sessions. The most common etiology was alcohol (53%). Sixty-eight percent of patients had grade 3 esophageal varices 76.5%had PHG. There was no immediate post-EVL bleeding or 30-day mortality. Variceal obliteration was achieved in 100% with 19% recurrence within amean period of53.74 ± 27.2months. PHG worsened in 49.7%. Overall, rebleeding occurred in 13.8%, 4.3% from recurrent varices. There was no difference in variceal recurrence (16.7% vs. 20%) and incidence of rebleeding (9.7% vs. 13.7%) between patients undergoing EVL for primary and secondary prophylaxis. Cumulative rebleeding rates after 1, 5, and 9years were 1.6%, 9.2%, and 11.4%, respectively. The overall mortality was 85%, mostly from progressive CLD, and only 8.6% was due to rebleeding. On subgroup analysis, the factors significantly associated with rebleeding was Child-Pugh class C and worsened PHG those with mortality were alcohol and Child-Pugh class C. EVL is effective in the long-term for both primary and secondary prophylaxis of esophageal variceal bleeding.

Use of nonselective β blockers after variceal eradication in cirrhotic patients undergoing secondary prophylaxis of esophageal variceal bleeding: a critical review of current evidence

Nonselective β blockers (NSBBs) combined with esophageal variceal ligation (EVL) are recommended for secondary prophylaxis of esophageal variceal bleeding (EVB) in cirrhotic patients according to the current practice guidelines and consensus. However, until now, there is a paucity of recommendations regarding the use of NSBBs in cirrhotic patients who achieved variceal eradication. In this review paper, we firstly introduced a case who achieved variceal eradication after additional use of NSBBs for secondary prophylaxis of EVB and then did not require further endoscopic therapy during repeated endoscopic surveillance, and subsequently discuss the importance of NSBBs for secondary prophylaxis of EVB, the effect of NSBBs after variceal eradication, adherence to NSBBs, screening for variceal recurrence, and timing of endoscopic surveillance after variceal eradication.

Non-invasive response prediction in prophylactic carvedilol therapy for cirrhotic patients with esophageal varices

Non-selective beta-blockers (NSBBs) are the mainstay of primary prophylaxis of esophageal variceal bleeding in patients with liver cirrhosis. We investigated whether non-invasive markers of portal hypertension correlate with hemodynamic responses to NSBBs in cirrhotic patients with esophageal varices. In this prospective cohort study, 106 cirrhotic patients with high-risk esophageal varices in the derivation cohort received carvedilol prophylaxis, and completed paired measurements of hepatic venous pressure gradient, liver stiffness (LS), and spleen stiffness (SS) at the beginning and end of dose titration. LS and SS were measured using acoustic radiation force impulse imaging. A prediction model for hemodynamic response was derived, and subject to an external validation in the validation cohort (63 patients). Hemodynamic response occurred in 59 patients (55.7%) in the derivation cohort, and in 33 patients (52.4%) in the validation cohort, respectively. Multivariate logistic regression analysis identified that ΔSS was the only significant predictor of hemodynamic response (odds ratio 0.039; 95% confidence interval 0.008-0.135; p <0.0001). The response prediction model (ModelΔSS = 0.0490-2.8345 × ΔSS; score = (exp[ModelΔSS])/(1 + exp[ModelΔSS]) showed good predictive performance (area under the receiver-operating characteristic curve [AUC] = 0.803) using 0.530 as the threshold value. The predictive performance of the ModelΔSS in the validation set improved using the same threshold value (AUC = 0.848). A new model based on dynamic changes in SS exhibited good performance in predicting hemodynamic response to NSBB prophylaxis in patients with high-risk esophageal varices. Non-selective beta-blockers are the mainstay of primary prophylaxis to prevent variceal bleeding in patients with cirrhosis and high-risk esophageal varices. This prospective study showed that a prediction model based on changes in spleen stiffness before vs. after dose titration might be a non-invasive marker for response to prophylactic non-selective beta-blocker (carvedilol) therapy in patients with cirrhosis and high-risk esophageal varices. ClinicalTrials.gov Identifier: NCT01943318.

Endoscopic variceal ligation combined with argon plasma coagulation versus ligation alone for the secondary prophylaxis of variceal bleeding: a systematic review and meta-analysis.

Endoscopic variceal ligation (EVL) is often recommended as an effective method for the treatment of esophageal varices, despite the important tendency of variceal recurrence. Recent studies indicate that combining EVL with argon plasma coagulation (APC) may be a more effective therapy than ligation alone. To investigate these findings, we carried out a systematic review and meta-analysis to compare the safety and efficacy of EVL combined with APC versus ligation alone for the secondary prophylaxis of esophageal variceal hemorrhage. All studies were searched through PubMed, the Cochrane Library, and Science Direct. The outcome measures were relative risk (RR) or risk difference with 95% confidence intervals (CIs) for dichotomous data and standardized mean difference for continuous data. Heterogeneity was calculated using the χ and the I-tests. Two investigators independently identified four randomized-controlled trials included in the research. The variceal recurrence rate was significantly lower in the combined therapy group (RR=0.19, 95% CI: 0.09-0.41, P=0.000). The bleeding recurrence and mortalities in the two groups showed no significant differences (RR=0.29, 95% CI: 0.08-1.04, P=0.058; risk difference=-0.02, 95% CI: -0.08-0.04, P=0.576, respectively). Although the pyrexia incidence rate was significantly higher in the combined group (RR=3.42, 95% CI: 1.56-7.48, P=0.002), there was intertrial heterogeneity (I=52.5%, P=0.097). EVL combined with APC is superior to ligation alone for endoscopic variceal recurrence without severe adverse events in secondary prophylaxis against esophageal variceal bleeding. More high-quality studies are needed to strengthen this conclusion.