Contemporary concepts of prevention and management of gastroesophageal variceal bleeding in liver cirrhosis patients

This editorial describes the contemporary concepts of prevention and management of gastroesophageal variceal bleeding in liver cirrhosis(LC)patients according to the current guidelines.Gastroesophageal variceal bleeding is the most dangerous complication of portal hypertension in LC patients.Risk stratification and determination of an individual approach to the choice of therapeutic measures aimed at their prevention and management has emerged as one of the top concerns in modern hepatology.According to the current guidelines,in the absence of clinically significant portal hypertension,etiological and nonetiological therapies of LC is advisable for the primary preventing gastroesophageal variceal bleeding,whereas its presence serves as an indication for the administration of non-selectiveβ-blockers,among which carvedilol is the drug of choice.Non-selectiveβ-blockers,as well as endoscopic variceal ligation and transjugular intrahepatic portosystemic shunt can be used to prevent recurrence of gastroesophageal variceal bleeding.Pharmacotherapy with vasoactive drugs(terlipressin,somatostatin,octreotide),endoscopic variceal ligation,endovascular techniques and transjugular intrahepatic portosystemic shunt are recommended for the treatment of acute gastroesophageal variceal bleeding.Objective and accurate risk stratification of gastroesophageal variceal bleeding will allow developing individual strategies for their prevention and management,avoiding the first and further decompensation in LC,which will improve the prognosis and survival of patients suffering from it.

Milestones to optimize of transjugular intrahepatic portosystemic shunt technique as a method for the treatment of portal hypertension complications

This editorial describes the milestones to optimize of transjugular intrahepatic portosystemic shunt(TIPS)technique,which have made it one of the main methods for the treatment of portal hypertension complications worldwide.Innovative ideas,subsequent experimental studies and preliminary experience of use in cirrhotic patients contributed to the introduction of TIPS into clinical practice.At the moment,the main achievement in optimize of TIPS technique is progress in the qualitative characteristics of stents.The transition from bare metal stents to extended polytetrafluoroethylene–covered stent grafts made it possible to significantly prevent shunt dysfunction.However,the question of its preferred diameter,which contributes to an optimal reduction of portal pressure without the risk of developing post-TIPS hepatic encephalopathy,remains relevant.Currently,hepatic encephalopathy is one of the most common complications of TIPS,significantly affecting its effectiveness and prognosis.Careful selection of patients based on cognitive indicators,nutritional status,assessment of liver function,etc.,will reduce the incidence of post-TIPS hepatic encephalopathy and improve treatment results.Optimize of TIPS technique has significantly expanded the indications for its use and made it one of the main methods for the treatment of portal hypertension complications.At the same time,there are a number of limitations and unresolved issues that require further randomized controlled trials involving a large cohort of patients.

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.

Endoscopic variceal ligation caused massive bleeding due to laceration of an esophageal varicose vein with tissue glue emboli

Endoscopic variceal obturation of gastric varices with tissue glue is considered the first choice for management of gastric varices, and is usually safe and effective. However, there is still a low incidence of complications and some are even fatal. Here, we present a case in which endoscopic variceal ligation caused laceration of the esophageal varicose vein with tissue glue emboli and massive bleeding after 3 mo. Cessation of bleeding was achieved via variceal sclerotherapy using a cap-fitted gastroscope. Methods of recognizing an esophageal varicose vein with tissue glue plug are discussed.

Timing of upper gastrointestinal endoscopy does not influence short-term outcomes in patients with acute variceal bleeding

AIM To examine the association between the timing of endo-scopy and the short-term outcomes of acute variceal bleeding in cirrhotic patients.METHODS This retrospective study included 274 consecutive patients admitted with acute esophageal variceal bleeding of two tertiary hospitals in Korea. We adjusted confounding factors using the Cox proportional hazards model and the inverse probability weighting （IPW） method. The primary outcome was the mortality of patients within 6 wk.RESULTS A total of 173 patients received urgent endoscopy （ i.e. , ≤ 12 h after admission）, and 101 patients received non-urgent endoscopy （〉 12 h after admission）. The 6-wk mortality rate was 22.5% in the urgent endoscopy group and 29.7% in the non-urgent endoscopy group, and there was no significant difference between the two groups before （P = 0.266） and after IPW （P = 0.639）. The length of hospital stay was statistically different between the urgent group and non-urgent group （P = 0.033）; however, there was no significant difference in the in-hospital mortality rate between the two groups （8.1%vs 7.9%, P = 0.960）. In multivariate analyses, timing of endoscopy was not associated with 6-wk mortality （hazard ratio, 1.297; 95% confdence interval, 0.806-2.089; P = 0.284）.CONCLUSION In cirrhotic patients with acute variceal bleeding, the timing of endoscopy may be independent of short-term mortality.

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.

Four-dimensional flow magnetic resonance imaging for noninvasive diagnosis of clinically significant portal hypertension and high-risk gastroesophageal varices in patients with cirrhosis

Introduction:Noninvasive diagnoses of clinically significant portal hypertension(CSPH)and high-risk gastroesophageal varices are clinically relevant but challenging.Four-dimensional(4D)flow magnetic resonance imaging(MRI)provides comprehensive flow information and is a promising alternative.This study evaluated the efficacy of 4D flow MRI as a noninvasive method for diagnosing CSPH and high-risk varices in patients with liver cirrhosis.Methods:This prospective study enrolled consecutive patients diagnosed with liver cirrhosis at a tertiary referral center between October 2020 and March 2021.Each participant underwent abdominal 4D flow MRI.Hemodynamic parameters within the portal vein,including the average and peak flow velocities,normalized flow volume(Q_(normal)),and regurgitant fraction(R%),were extracted and compared between healthy individuals and patients with CSPH and between participants with high-and low-risk varices.Subsequently,these parameters were incorporated into a logistic regression(LR)model refined using L1 regularization and validated using five-fold cross-validation.The diagnostic efficacy was evaluated using receiver operating characteristic(ROC)curves.Results:Eighty-two participants were enrolled(71 patients diagnosed with liver cirrhosis and 11 healthy individuals serving as controls).Among hemodynamic parameters,patients with CSPH exhibited a notable increase in Q_(normal)of 0.66±0.19 ml*m^(2)/[cycle*kg](P=0.001)and an R%of 1.98(2.05)(P=0.002).Similarly,patients with high-risk varices showed a higher Q_(normal)of 0.61±0.15 ml*m^(2)/[cycle*kg](P<0.001)and R%of 1.88(2.81)(P=0.006).ROC analysis revealed an area under the curve(AUC)for Q_(normal)of 0.93 and 0.91 for R%for diagnosing CSPH,while the LR model showcased a superior AUC of 0.95.For high-risk varices,Q_(normal)and R%showed AUC values of 0.75 and 0.70,respectively,whereas the LR model showed a higher AUC of 0.84.Conclusion:As a noninvasive imaging modality,4D flow MRI exhibits considerable potential for the diagnosis of CSPH and high-risk gastroesophageal varices;thus,it may minimize the reliance on invasive procedures in patients with cirrhosis.

Utility of endoscopic ultrasound in patients with portal hypertension

Endoscopic ultrasound(EUS) has revolutionized the diagnostic and therapeutic approach to patients with gastrointestinal disorders. Its application in patients with liver disease and portal hypertension is increasing. Patients with chronic liver disease are at risk for development of portal hypertension sequale such as ascites, spontaneous bacterial peritonitis and gastroesophageal varices. Bleeding esophageal and gastric varices are among the most common causes of mortality in patients with cirrhosis. Thus, early detection and treatment improve the outcome in this population. EUS can improve the detection and diagnosis of gastroesophageal varices and collateral veins and can provide endoscopic therapy of gastroesophageal varices such as EUS-guided sclerotherapy of esophageal collateral vessels and EUS-guided cynoacrylate(Glue) injection of gastric varices. EUS can also provide knowledge on the efficacy of pharmacotherapy of portal hypertension. Furthermore, EUS can provide assessment and prediction of variceal recurrence after endoscopic therapy and assessment of portal hemodynamics such as E-Flow and Doppler study of the azygous and portal veins. Moreover, EUS-guided fine needle aspiration may provide cytologic diagnosis of focal hepatic tumors andanalysis of free abdominal fluid.Using specialized EUSguided needle biopsy,a sample of liver tissue can be obtained to diagnose and evaluate for chronic liver disease.EUS-guided fine needle injection can be used to study portal vein pressure and hemodynamics,and potentially could be used to assist in exact measurement of portal vein pressure and placement of intrahepatic portosystemic shunt.

Noninvasive scores for the prediction of esophageal varices and risk stratification in patients with cirrhosis

The primary purpose of variceal screening in patients with cirrhosis is to detect gastroesophageal varices at high risk of hemorrhage and implement preventative intervention(s).It was previously recommended that all patients with cirrhosis undergo initial and periodic longitudinal variceal screening via upper endoscopy.However,there has been growing interest and methods to identify patients with cirrhosis who may not have clinically significant portal hypertension and therefore be unlikely to have varices requiring intervention or benefit from upper endoscopy.Because the population of patients with compensated advanced chronic liver disease continues to grow,it is neither beneficial nor cost-effective to perform endoscopic variceal screening in all patients.Therefore,there is ongoing research into the development of methods to non-invasively risk stratify patients with cirrhosis for the presence of high-risk esophageal varices and effectively limit the population that undergoes endoscopic variceal screening.This is particularly important and timely in light of increasing healthcare reform and barriers to healthcare.In this review,we discuss and compare,with respect to test characteristics and clinical applicability,the available methods used to noninvasively predict the presence of esophageal varices.

Endoscopic submucosal tunnel dissection for early esophageal squamous cell carcinoma in patients with cirrhosis:A propensity score analysis

BACKGROUND Although early esophageal squamous cell carcinoma(EESCC)with cirrhosis is a relatively rare clinical phenomenon,the management of EESCC in cirrhotic patients continues to be a challenge.AIM To evaluate the feasibility,safety,efficacy and long-term survival outcomes of endoscopic submucosal tunnel dissection(ESTD)for treating EESCC in patients with cirrhosis.METHODS This was a single-center retrospective cohort study.We examined 590 EESCC patients who underwent ESTD between July 14,2014,and May 26,2021,from a large-scale tertiary hospital.After excluding 25 patients with unclear lesion areas or pathological results,the remaining 565 patients were matched at a ratio of 1:3 by using propensity score matching.A total of 25 EESCC patients with comorbid liver cirrhosis and 75 matched EESCC patients were ultimately included in the analysis.Parametric and nonparametric statistical methods were used to compare the differences between the two groups.The Kaplan–Meier method was used to create survival curves,and differences in survival curves were compared by the log-rank test.RESULTS Among 25 patients with liver cirrhosis and 75 matched noncirrhotic patients,there were no significant differences in intraoperative bleeding(P=0.234),30-d post-ESTD bleeding(P=0.099),disease-specific survival(P=0.075),or recurrence-free survival(P=0.8196).The mean hospitalization time and costs were significantly longer(P=0.007)and higher(P=0.023)in the cirrhosis group than in the noncirrhosis group.The overall survival rate was significantly lower in the cirrhosis group(P=0.001).CONCLUSION ESTD is technically feasible,safe,and effective for patients with EESCC and liver cirrhosis.EESCC patients with Child-Pugh A disease seem to be good candidates for ESTD.

Gastrointestinal endoscopy in cirrhotic patient:Issues on the table

Patients with liver cirrhosis are fragile and present specific clinical hallmarks.When undergoing to gastrointestinal(GI)endoscopy,these subjects require an individual pre evaluation,taking into account:Level of haemostasis impairment,the individual risk of infection,the impact of sedation on hepatic encephalopathy and other factors.The overall assessment of liver function,employing common scoring systems,should be also assessed in the preprocedural phase.Beside some common general problems,regarding GI endoscopy in cirrhotic subjects,also specific issues are present for some frequent indications or procedures.For instance,despite an increased incidence of adenomas in cirrhosis,colon cancer screening remains suboptimal in subjects with this disease.Several studies in fact demonstrated liver cirrhosis as a negative factor for an adequate colon cleansing before colonoscopy.On the other hand,also the routine assessment of gastroesophageal varices during upper GI endoscopy presents some concern,since important inter-observer variability or incomplete description of endoscopic findings has been reported in some studies.In this review we discussed in details the most relevant issues that may be considered while performing general GI endoscopic practice,in patient with cirrhosis.For most of these issues there are no guidelines or clear indications.Moreover until now,few studies focused on these aspects.We believe that targeting these issues with corrective measures may be helpful to develop a tailored endoscopic approach for cirrhosis,in the future.

Endoscopic ultrasonography-emerging applications in hepatology

The inspection of the liver is a valuable part of the upper endoscopic ultrasonography(EUS) studies,regardless of the primary indication for the examination.The detailed images of the liver segments provided by EUS allows the use of this technique in the study of parenchymal liver disease and even in the diagnosis and classification of focal liver lesions.EUS has also emerged as an important tool in understanding the complex collateral circulation in patients with portal hypertension and their clinical and prognostic value.Recently,EUS-guided portal vein catheterization has been performed for direct portal pressure measurement as an alternative method to evaluate portal hemodynamics.In this review,the authors summarize the available evidence regarding the application of EUS to patients with liver diseases and how we can apply it in our current clinical practice.

Effects of proton pump inhibitor on gastroesophageal varices in patients with cirrhosis:A randomized controlled trial from China

Aims:Proton pump inhibitors(PPI)are widely used for gastroesophageal varices in patients with cirrhosis after endoscopic therapy,although the effect of PPI on these patients remains controversial.This study aimed to evaluate the effect of PPI on gastroesophageal varices in patients with cirrhosis after endoscopic therapy,including variceal bleeding and adverse events.Methods:Cirrhotic patients with endoscopically confirmed gastroesophageal varices were enrolled in this study between May 2017 and June 2019.Eligible patients were randomized into two groups:one group received PPI for 14 days and the other group did not receive PPI treatment(n=53 in each group).All patients were followed for 8 weeks.Results:During the follow‐up period,three patients(5.66%)in the PPI group experienced variceal bleeding on days 9,16,and 25 after endoscopic therapy,including two patients with acute bleeding and one with primary prophylaxis.In the non‐PPI group,three patients(5.66%)experienced variceal bleeding on days 7,42,and 56 after endoscopic therapy,including one patient with acute bleeding and two with secondary prophylaxis(p=0.990).The incidence of adverse events was similar between the two groups(37.74%vs.28.30%,p=0.30).Conclusions:PPI did not appear to reduce variceal bleeding and adverse events in patients with cirrhosis after endoscopic therapy.

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）.

Impact of endoscopic ultrasound examination for deep esophageal collateral veins evaluation in liver cirrhosis patients prior to endoscopic treatment:A case series

Aim:The presence of esophageal collateral veins(ECV)has been reported to be associated with the recurrence of esophageal varices(EV)and bleeding in liver cirrhotic(LC)patients.This study aimed to see the potential clinical value of deep collateral veins assessment using endoscopic ultrasound(EUS)in liver cirrhotic patients with EV.Methods:During 6 months period,a prospective study is conducted,where we identified LC patients who were admitted for esophagogastroduodenoscopy(EGD)screening at the Department of Internal Medicine,Dr.Cipto Mangunkusumo National General Hospital,Jakarta.ECV was examined using EUS.Patients were excluded if they had(1)liver malignancy,(2)history of ligation or glue injection,or(3)portal or splenic vein thrombus.We collected demographic data,medical history,data pertaining to use of nonselective beta blocker(NSBB),and laboratory,imaging,and endoscopy results.EGD was performed using a gastroscope(EG29‐i10,3.2 mm Pentax Medical)while EUS was performed using a linear array echoendoscope(EG‐3870UTK,3.8 mm,Pentax Medical)before band ligation or glue injection.Results:There were 20 LC patients included in this study,where 15(75%)of patients were classified with Child-Pugh(CP)‐A and five(25%)of patients with CP‐B.The most common aetiologies were hepatitis B in seven(35%)patients and hepatitis C in nine(45%)patients.The EV with peri‐or para‐esophageal veins(PEEV or PAEV)were detected in 65%of patients.None of the LC patients with no EV showed the presence of ECV.PEEV or PAEV were detected in grades 1-3 EV.Conclusion:EUS examination can give a better evaluation before managing gastroesophageal varices through deep ECV detection in LC patients.