Defining the advantages and exposing the limitations of endoscopic variceal ligation in controlling acute bleeding and achieving complete variceal eradication

BACKGROUND Bleeding esophageal varices(BEV)is a potentially life-threatening complication in patients with portal hypertension with mortality rates as high as 25%within six weeks of the index variceal bleed.After control of the initial bleeding episode patients should enter a long-term surveillance program with endoscopic intervention combined with non-selectiveβ-blockers to prevent further bleeding and eradicate EV.AIM To assess the efficacy of endoscopic variceal ligation(EVL)in controlling acute variceal bleeding,preventing variceal recurrence and rebleeding and achieving complete eradication of esophageal varices(EV)in patients who present with BEV.METHODS A prospectively documented single-center database was used to retrospectively identify all patients with BEV who were treated with EVL between 2000 and 2018.Control of acute bleeding,variceal recurrence,rebleeding,eradication and survival were analyzed using Baveno assessment criteria.RESULTS One hundred and forty patients(100 men,40 women;mean age 50 years;range,21-84 years;Child-Pugh grade A=32;B=48;C=60)underwent 160 emergency and 298 elective EVL interventions during a total of 928 endoscopy sessions.One hundred and fourteen(81%)of the 140 patients had variceal bleeding that was effectively controlled during the index banding procedure and never bled again from EV,while 26(19%)patients had complicated and refractory variceal bleeding.EVL controlled the acute sentinel variceal bleed during the first endoscopic intervention in 134 of 140 patients(95.7%).Six patients required balloon tamponade for control and 4 other patients rebled in hospital.Overall 5-d endoscopic failure to control variceal bleeding was 7.1%(n=10)and four patients required a salvage transjugular intrahepatic portosystemic shunt.Index admission mortality was 14.2%(n=20).EV were completely eradicated in 50 of 111 patients(45%)who survived>3 mo of whom 31 recurred and 3 rebled.Sixteen(13.3%)of 120 surviving patients subsequently had 21 EV rebleeding episodes and 10 patients bled from other sources after discharge from hospital.Overall rebleeding from all sources after 2 years was 21.7%(n=26).Sixty-nine(49.3%)of the 140 patients died,mainly due to liver failure(n=46)during follow-up.Cumulative survival for the 140 patients was 71.4%at 1 year,65%at 3 years,60%at 5 years and 52.1%at 10 years.CONCLUSION EVL was highly effective in controlling the sentinel variceal bleed with an overall 5-day failure to control bleeding of 7.1%.Although repeated EVL achieved complete variceal eradication in less than half of patients with BEV,of whom 62%recurred,there was a significant reduction in subsequent rebleeding.

Comparative study for predictability of type 1 gastric variceal rebleeding after endoscopic variceal ligation:High-frequency intraluminal ultrasound study

BACKGROUND The efficacy of endoscopic ultrasonography for the follow-up of gastric varices treated with endoscopic variceal ligation(EVL)has not been established.AIM To evaluate the diagnostic correlation of esophagogastroduodenoscopy(EGD)and high-frequency intraluminal ultrasound(HFIUS)for type 1 gastric varices(GOV1)after EVL and to identify the predictability for rebleeding of EGD and HFIUS.METHODS In liver cirrhosis patients with GOV1,we performed endoscopic follow-up using EGD and HFIUS synchronously after EVL for hemorrhage from GOV1.Endoscopic grading and red color signs were analyzed using EGD,and the largest variceal cross-sectional areas were measured using HFIUS.In addition,1-year follow-up was performed.Variceal rebleeding was defined as the presence of hematemesis,hematochezia,or melena without other evidence of bleeding on endoscopic follow-up.RESULTS In 26 patients with GOV1,variceal cross-sectional areas on HFIUS of GOV1 was poorly correlated with EGD grading of GOV1(r=0.36).In 17 patients who completed the 1-year follow-up,variceal cross-sectional areas on HFIUS was a good predictor of subsequent rebleeding,whereas EGD grading was not a predictor of subsequent rebleeding.CONCLUSION HFIUS measurement is more predictive of GOV1 rebleeding than EGD grading,so HFIUS measurement may be necessary for endoscopic follow-up after EVL in patients with GOV1.

Effect of aluminum phosphate gel on prevention of early rebleeding after ligation of esophageal variceal hemorrhage

BACKGROUND Liver cirrhosis is the main cause of portal hypertension.The leading cause of death in patients with liver cirrhosis is its most common complication,esophageal variceal bleeding(EVB).Endoscopic variceal ligation(EVL)is recommended by many guidelines to treat EVB and prevent rebleeding;however,esophageal ulcers occur after treatment.Delayed healing of ulcers and unhealed ulcers lead to high rebleeding and mortality rates.Thus,the prevention of early postoperative rebleeding is of great significance in improving the quality of life and prognosis of patients.AIM To evaluate the efficacy of aluminum phosphate gel(APG)plus a proton pump inhibitor(PPI)in the prevention of early rebleeding after EVL in patients with EVB.METHODS The medical records of 792 patients who were diagnosed with EVB and in whom bleeding was successfully stopped by EVL at Shenzhen People’s Hospital,Guangdong Province,China from January 2015 to December 2020 were collected.According to the study inclusion and exclusion criteria,401 cases were included in a PPI-monotherapy group(PPI group),and 377 cases were included in a PPI and APG combination therapy(PPI+APG)group.We compared the incidence rates of early rebleeding and other complications within 6 wk after treatment between the two groups.The two-sample t-test,Wilcoxon rank-sum test,and chisquared test were adopted for statistical analyses.RESULTS No significant differences in age,sex,model for end-stage liver disease score,coagulation function,serum albumin level,or hemoglobin level were found between the two groups.The incidence of early rebleeding in the PPI+APG group(9/337;2.39%)was significantly lower than that in the PPI group(30/401;7.48%)(P=0.001).Causes of early rebleeding in the PPI group were esophageal ulcer(3.99%,16/401)and esophageal varices(3.49%,14/401),while those in the PPI+APG group were also esophageal ulcers(5/377;1.33%)and esophageal varices(4/377;1.06%);such causes were significantly less frequent in the PPI+APG group than in the PPI group(P=0.022 and 0.024,respectively).The early mortality rate within 6 wk in both groups was 0%,which was correlated with the timely rehospitalization of all patients with rebleeding and the conduct of emergency endoscopic therapy.The incidence of adverse events other than early bleeding in the PPI+APG group(28/377;7.43%)was significantly lower than that in the PPI group(63/401;15.71%)(P<0.001).The incidence of chest pain in the PPI+APG group(9/377;2.39%)was significantly lower than that in the PPI group(56/401;13.97%)(P<0.001).The incidence of constipation in the PPI+APG group(16/377;4.24%)was significantly higher than that in the PPI group(3/401;0.75%)(P=0.002)but constipation was relieved after patients drank more water or took lactulose.In the PPI and PPI+APG groups,the incidence rates of spontaneous peritonitis within 6 wk after discharge were 0.50%(2/401)and 0.53%(2/377),respectively,and those of hepatic encephalopathy were 0.50%(2/401)and 0.27%(1/377),respectively,presenting no significant difference(P>0.999).CONCLUSION PPI+APG combination therapy significantly reduces the incidence of early rebleeding and chest pain in patients with EVB after EVL.

Embolization combined with endoscopic variceal ligation for the treatment of esophagogastric variceal bleeding in patients with cirrhosis

Background Esophagogastric variceal bleeding caused by cirrhosis is a kind of emergent condition in the clinic. This study was conducted to explore the therapeutic effect and superiority of embolization of gastric fundus vadces combined with endoscopic variceal ligation （EVL） of esophageal varices for the treatment of patients with esophagogastric variceal bleeding caused by cirrhosis. Methods Totally 172 patients were diagnosed by endoscopic examination within 24 hours of hospitalization with active gastric fundus variceal bleeding and grade II above esophageal varices caused by cirrhosis. Other causes leading to upper digestive tract bleeding were excluded. Patients were randomly divided into a control group （n=82） and a therapy group （n=-90） following a random number table method. For the former, embolization for gastric fundus varices was performed, then an EVL for esophageal varices was performed 2 months later. For the therapy group, embolization for gastric fundus varices and EVL for esophageal varices were performed at the same time. Results The rate of emergency hemostasis in the therapy group was 100.0%, higher than that in the control group （87.8%, P〈0.05）. The rate of early rebleeding in the therapy group was 6.7% while the rate in the control group was 23.6% （P〈0.05）. No complications related to treatment occurred in both groups. Conclusion Embolization for gastric fundus varices combined with EVL for esophageal varices is a safe and effective method for the treatment of patients with esophagogastric variceal bleeding caused by cirrhosis.

Case Control Study of Post-endoscopic Variceal Ligation Bleeding Ulcers in Severe Liver Disease: Outcomes and Management

Background and Aims:The management of post-endoscopic variceal ligation(EVL)bleeding ulcers(PEBUs)is currently based on local expertise and patients liver disease status.The present retrospective study investigated associations between the endoscopic morphology of PEBUs and patient outcomes.Methods:Patients underwent EVL(primary or secondary),from January 2015 to January 2018,in two tertiary care hospitals in India(ILBS New Delhi and Dharamshila Narayana New Delhi).Mortality rates were determined at post-EVL day five and week six.PEBUs were typified based on Jamwal&Sarin classification system as follows:A,ulcer with active spurting;B,ulcer with ooze;C,ulcer base with visible vessel or clot;and D,clean or pigmented base.Results:Of 3854 EVL procedures,141(3.6%)patients developed PEBU,and 46/141(32.6%)suffered mortality.Among the former,the PEBU types A,B,C,and D accounted for 17.7,26.2,36.3,and 19.8%,respectively.Of those who died,39.1,30.4,21.7,and 8.8%had PEBU types A,B,C,and D.Treatments included transjugular intrahepatic portosystemic shunts(TIPS),esophageal self-expandable metal stent(SEMS),glue and sclerosant injection,Sengstaken-Blakemore tube placement and liver transplant.On univariate analysis,no correlation with hepatic venous pressure gradient,TIPS placement,size of varices,or number of bands was found.The Model for EndStage Liver Disease(MELD)-sodium score correlated positively with outcome.After adjusting for MELD-sodium score,mortality was best predicted by type-A ulcer(p=0.024;OR 8.95,CI 1.34-59.72).Conclusions:PEBU occurred in 3.6%of a large EVL cohort.Stratifying patients based on PEBU type can help predict outcomes,independent of the MELD-sodium score.Classifying PEBUs by endoscopic morphology may inform treatment strategies,and warrants further validation.

Primary prophylaxis of variceal bleeding in patients with cirrhosis:A comparison of different strategies

Patients with cirrhosis and esophageal varices bleed at a yearly rate of 5%-15%,and,when variceal hemorrhage develops,mortality reaches 20%.Patients are deemed at high risk of bleeding when they present with medium or large-sized varices,when they have red signs on varices of any size and when they are classified as Child-Pugh C and have varices of any size.In order to avoid variceal bleeding and death,individuals with cirrhosis at high risk of bleeding must undergo primary prophylaxis,for which currently recommended strategies are the use of traditional non-selective beta-blockers(NSBBs)(i.e.,propranolol or nadolol),carvedilol(a NSBB with additional alpha-adrenergic blocking effect)or endoscopic variceal ligation(EVL).The superiority of one of these alternatives over the others is controversial.While EVL might be superior to pharmacological therapy regarding the prevention of the first bleeding episode,either traditional NSBBs or carvedilol seem to play a more prominent role in mortality reduction,probably due to their capacity of preventing other complications of cirrhosis through the decrease in portal hypertension.A sequential strategy,in which patients unresponsive to pharmacological therapy would be submitted to endoscopic treatment,or the combination of pharmacological and endoscopic strategies might be beneficial and deserve further investigation.

Gastroesophageal varices in a patient presenting with essential thrombocythemia:A case report

BACKGROUND Gastroesophageal varices are a rare complication of essential thrombocythemia(ET).ET is a chronic myeloproliferative neoplasm(MPN)characterized by an increased number of blood platelets.CASE SUMMARY A 46-year-old woman,who denied a history of liver disease,was admitted to our hospital on presentation of hematemesis.Laboratory examination revealed a hemoglobin level of 83 g/L,and a platelet count of 397×109/L.The appearance of gastric and esophageal varices with red colored signs as displayed by an urgent endoscopy was followed by endoscopic variceal ligation and endoscopic tissue adhesive.Abdominal computed tomography revealed cirrhosis,marked splenomegaly,portal vein thrombosis and portal hypertension.In addition,bone marrow biopsy and evidence of mutated Janus kinase 2,substantiated the onset of ET.The patient was asymptomatic with regular routine blood testing during the 6-mo follow-up period.Therefore,in this case,gastroesophageal varices were induced by ET.CONCLUSION MPN should be given considerable attention when performing differential diagnoses in patients with gastroesophageal varices.An integrated approach such as laboratory tests,radiological examination,and pathological biopsy,should be included to allow optimal decisions and management.

β-arrestin-2 predicts the clinical response to β-blockers in cirrhotic portal hypertension patients: A prospective study

BACKGROUND Portal hypertension,a common complication associated with liver cirrhosis,can result in variceal bleeding,which greatly impacts patient survival.Recently,β-arrestin-2 has been shown to predict the acute hemodynamic response to nonselectiveβ-blocker therapy for cirrhotic portal hypertension.However,more data is needed on the long-term effects of and changes inβ-arrestin-2 following nonselectiveβ-blocker therapy.AIM To investigate the expression and role ofβ-Arrestin-2 in predicting the long-term response to nonselectiveβ-blockers in cirrhotic portal hypertensive patients.METHODS We prospectively enrolled 91 treatment-naïve patients with cirrhotic portal hypertension.Baseline clinical and laboratory data were obtained.Gastroscopy was performed for grading and treating varices and obtaining gastric antral biopsies.We measured the serum and antral expression ofβ-arrestin-2 and obtained Doppler measurement of the portal vein congestion index.Treatment with nonselectiveβ-blockers was then started.The patients were followed up for 18 mo,after which they have undergone a repeat antral biopsy and re-evaluation of the portal vein congestion index.RESULTS A higher serum level and antral expression ofβ-arrestin-2 was associated with longer bleedingfree intervals,greater reduction in the portal vein congestion index,and improved grade of varices.Among patients with a lowβ-arrestin-2 expression,17.6%were nonselectiveβ-blocker responders,whereas,among those with high expression,95.1%were responders(P<0.001).A serumβ-arrestin-2 value≥2.23 ng/mL was associated with a lower likelihood of variceal bleeding(90%sensitivity and 71%specificity).β-arrestin-2 expression significantly decreased after nonselectiveβ-blocker therapy.CONCLUSIONβ-arrestin-2 expression in cirrhotic portal hypertension predicts the clinical response to long-term nonselectiveβ-blocker treatment.Serumβ-arrestin-2 is a potential noninvasive biomarker for selecting the candidate patients for nonselectiveβ-blockers.

Unpacking the challenge of gastric varices: A review on indication, timing and modality of therapy

Upper gastrointestinal bleeding from oesophageal or gastric varices is an important medical condition in patients with portal hypertension.Despite the emergence of a number of novel endoscopic and radiologic therapies for oesophagogastric varices,controversy exists regarding the indication,timing and modality of therapy.The aim of this review is to provide a concise and practical evidence-based overview of these issues.

Reinforcing the management of type 1 gastric esophageal varices

Variceal bleed represents an important complication of cirrhosis,with its presence reflecting the severity of liver disease.Gastric varices,though less frequently seen than esophageal varices,present a distinct clinical challenge due to its higher intensity of bleeding and associated mortality.Based upon the Sarin classification,GOV1 is the most common subtype of gastric varices seen in clinical practice.

Sequential therapy for patients with cirrhosis complicated by common bile duct stones and moderate to severe gastroesophageal varices

Cirrhosis complicated by common bile duct stones is a common clinical finding.1 Currently, good therapeutic results occur in patients with cirrhosis complicated by moderate to severe gastroesophageal varices and common bile duct stones using endoscopic variceal ligation （EVL） and/or embolization followed two weeks later by calculus removal with endoscopic retrograde cholangiopancreatography （ERCP）.