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.

Effectiveness of antibiotic prophylaxis for acute esophageal variceal bleeding in patients with band ligation: A large observational study

BACKGROUND Esophageal variceal bleeding is a severe complication associated with liver cirrhosis and typically necessitates endoscopic hemostasis.The current standard treatment is endoscopic variceal ligation(EVL),and Western guidelines recom-mend antibiotic prophylaxis following hemostasis.However,given the impro-vements in prognosis for variceal bleeding due to advancements in the management of bleeding and treatments of liver cirrhosis and the global concerns regarding the emergence of multidrug-resistant bacteria,there is a need to reassess the use of routine antibiotic prophylaxis after hemostasis.AIM To evaluate the effectiveness of antibiotic prophylaxis in patients treated for EVL.METHODS We conducted a 13-year observational study using the Tokushukai medical database across 46 hospitals.Patients were divided into the prophylaxis group(received antibiotics on admission or the next day)and the non-prophylaxis group(did not receive antibiotics within one day of admission).The primary outcome was composed of 6-wk mortality,4-wk rebleeding,and 4-wk spontaneous bacterial peritonitis(SBP).The secondary outcomes were each individual result and in-hospital mortality.A logistic regression with inverse probability of treatment weighting was used.A subgroup analysis was conducted based on the Child-Pugh classification to determine its influence on the primary outcome measures,while sensitivity analyses for antibiotic type and duration were also performed.RESULTS Among 980 patients,790 were included(prophylaxis:232,non-prophylaxis:558).Most patients were males under the age of 65 years with a median Child-Pugh score of 8.The composite primary outcomes occurred in 11.2%of patients in the prophylaxis group and 9.5%in the non-prophylaxis group.No significant differences in outcomes were observed between the groups(adjusted odds ratio,1.11;95%confidence interval,0.61-1.99;P=0.74).Individual outcomes such as 6-wk mortality,4-wk rebleeding,4-wk onset of SBP,and in-hospital mortality were not significantly different between the groups.The primary outcome did not differ between the Child-Pugh subgroups.Similar results were observed in the sensitivity analyses.CONCLUSION No significant benefit to antibiotic prophylaxis for esophageal variceal bleeding treated with EVL was detected in this study.Global reassessment of routine antibiotic prophylaxis is imperative.

Predictors of esophageal varices and first variceal bleeding in liver cirrhosis patients

To assess “predictors” of esophageal varices (EV) and variceal bleeding using non-invasive markers in Albanian patients diagnosed with liver cirrhosis. METHODSOne hundred thirty-nine newly diagnosed cirrhotic patients without variceal bleeding were included in this analysis. Model for end-stage liver disease (MELD), aspartate aminotransferase (AST) to alanine aminotransferase (ALT) ratio (AST/ALT), AST to platelet ratio index (APRI), platelet count to spleen diameter (PC/SD), fibrosis-4-index (FIB-4), fibrosis index (FI) and King’s Score were measured for all participants. All patients underwent endoscopic assessment within two days of hospitalization. The major end point was the first esophageal variceal bleeding (EVB) event. The diagnostic performance of “predictors” for the presence of EV and EVB were assessed by sensitivity and specificity values obtained from the receiver operating characteristics procedure. RESULTSFIB-4 was the only strong and significant “predictor” of esophageal varices (multivariable-adjusted OR = 1.57 for one unit increment; 95%CI: 1.15-2.14). Furthermore, a cut-off value of 3.23 for FIB-4 was a significant predictor of esophageal varices, with a sensitivity of 72%, a specificity of 58% and a proportion of area under the curve (AUC) of 66% (P = 0.01). During the follow-up (median: 31.5 mo; interquartile range: 11-59 mo), 34 patients (24%) experienced a first EVB. FIB-4 was a poor predictor of EVB (the AUC was only 51%) for a cut-off value of 5.02. Furthermore, the AUC of AST/ALT, APRI, PC/SD, FI, MELD and King’s Score ranged from 45% to 55%. None of the non-invasive markers turned out to be a useful predictor of EVB. CONCLUSIONDespite the low diagnostic accuracy, FIB-4 appears the most efficient non-invasive liver fibrosis marker which can be used as an initial screening tool for cirrhotic patients.

Endoscopic treatment of esophageal varices in patients with liver cirrhosis

Variceal bleeding is a life-threatening complication of portal hypertension with a six-week mortality rate of approximately 20%. Patients with medium- or largesized varices can be treated for primary prophylaxis of variceal bleeding using two strategies: non-selective beta-blockers(NSBBs) or endoscopic variceal ligation(EVL). Both treatments are equally effective. Patients with acute variceal bleeding are critically ill patients. The available data suggest that vasoactive drugs, combined with endoscopic therapy and antibiotics, are the best treatment strategy with EVL being the endoscopic procedure of choice. In cases of uncontrolled bleeding, transjugular intrahepatic portosystemic shunt(TIPS) with polytetrafluoroethylene(PTFE)-covered stents are recommended. Approximately 60% of the patients experience rebleeding, with a mortality rate of 30%. Secondary prophylaxis should start on day six following the initial bleeding episode. The combination of NSBBs and EVL is the recommended management, whereas TIPS with PTFE-covered stents are the preferred option in patients who fail endoscopic and pharmacologic treatment. Apart from injection sclerotherapy and EVL, other endoscopic procedures, including tissue adhesives, endoloops, endoscopic clipping and argon plasma coagulation, have been used in the management of esophageal varices. However, their efficacy and safety, compared to standard endoscopic treatment, remain to be further elucidated. There are safety issues accompanying endoscopic techniques with aspiration pneumonia occurring at a rate of approximately 2.5%. In conclusion, future research is needed to improve treatment strategies, including novel endoscopic techniques with better efficacy, lower cost, and fewer adverse events.

Hemodynamic analysis of esophageal varices in patients with liver cirrhosis using color Doppler ultrasound

AIM： To study the portal hemodynamics and their relationship with the size of esophageal varices seen at endoscopy and to evaluate whether these Doppler ultrasound parameters might predict variceal bleeding in patients with liver cirrhosis and portal hypertension. METHODS： One hundred and twenty cirrhotic patients with esophageal varices but without any previous bleeding were enrolled in the prospective study. During a 2-year observation period, 52 patients who had at least one episode of acute esophageal variceal hemorrhage constituted the bleeding group, and the remaining 68 patients without any previous hemorrhage constituted the non-bleeding group. All patients underwent endoscopy before or after color Doppler-ultrasonic examination, and images were interpreted independently by two endoscopists. The control group consisted of 30 healthy subjects, matched to the patient group in age and gender. Measurements of diameter, flow direction and flow velocity in the left gastric vein （LGV） and the portal vein （PV） were done in all patients and controls using color Doppler unit. After baseline measurements, 30 min after oral administration of 75 g glucose in 225 mL, changes of the diameter, flow velocity and direction in the PV and LGV were examined in 60 patients with esophageal varices and 15 healthy controls. RESULTS： The PV and LGV were detected successfully in 115 （96%） and 105 （88%） of 120 cirrhotic patients, respectively, and in 27 （90%） and 21 （70%） of 30 healthy controls, respectively. Among the 120 cirrhotic patients, 37 had F1, 59 had F2, and 24 had F3 grade varices. Compared with the healthy controls, cirrhotic group had a significantly lower velocity in the PV, a significantly greater diameter of the PV and LGV, and a higher velocity in the LGV. In the cirrhotic group, no difference in portal flow velocity and diameter were observed between patients with or without esophageal variceal bleeding （EVB）. However, the diameter and blood flow velocity of the LGV were significantly higher for EVB （＋） group compared with EVB （-） group （P〈0.01）. Diameter of the LGV increased with enlarged size of varices. There were differences between F1 and F2, F1 and F3 varices, but no differences between F2 and F3 varices （P = 0.125）. However, variceal bleeding was more frequent in patients with a diameter of LGV 〉6 mm. The flow velocity in the LGV of healthy controls was 8.70＋1.91 cm/s （n = 21）. In patients with liver cirrhosis, it was 10.3＋2.1 cm/s （n = 12） when the flow was hepatopetal and 13.5＋2.3 cm/s （n = 87） when it was hepatofugal. As the size of varices enlarged, hepatofugal flow velocity increased （P〈0.01） and was significantly different between patients with F1 and F2 varices and between patients with F2 and F3 varices. Variceal bleeding was more frequent in patients with a hepatofugal flow velocity 〉15 cm/s （32 of 52 patients, 61.5%）. Within the bleeding group, the mean LGV blood flow velocity was 16.6＋2.62 cm/s. No correlation was observed between the portal blood flow velocity and EVB. In all healthy controls, the flow direction in the LGV was hepatopetal, toward the PV. In patients with F1 varices, flow direction was hepatopetal in 10 patients, to-and-fro state in 3 patients, and hepatofugal in the remaining 18. The flow was hepatofugal in 91% patients with F2 and all F3 varices. Changes in diameter of the PV and LGV were not significant before and after ingestion of glucose （PV： 1.41＋1.5 cm before and 1.46＋1.6 cm after; LGV： 0.57＋1.7 cm before and 0.60＋1.5 cm after）. Flow direction in the LGV was hepatopetal and to-and-fro in 16 patients and hepatofugal in 44 patients before ingestion of glucose. Flow direction changed to hepatofugal in 9 of 16 patients with hepatopetal and to-and-fro blood flow after ingestion of glucose. In 44 patients with hepatofugal blood flow in the LGV, a significant increase in hepatofugal flow velocity was observed in 38 of 44 patients （86%） with esophageal varices. There was a relationship between the percentage changes in flow velocity and the size of varices. Patients who responded excessively to food ingestion might have a high risk for bleeding. The changes of blood flow velocity in the LGV were greater than those in the PV （LGV： 28.3＋26.1%, PV： 7.2＋13.2%, P〈0.01）, whereas no significant changes in the LGV occurred before and after ingestion of glucose in the control subjects. CONCLUSION： Hemodynamics of the PV is unrelated to the degree of endoscopic abnormalities in patients with liver cirrhosis. The most important combinations are endoscopic findings followed by the LGV hemodynamics. Duplex-Doppler ultrasonography has no value in the identification of patients with cirrhosis at risk of variceal bleeding. Hemodynamics of the LGV appears to be superior to those of the PV in predicting bleeding.

Efficacy of transjugular intrahepatic portosystemic shunts in treating cirrhotic esophageal-gastric variceal bleeding

BACKGROUND Esophageal-gastric variceal bleeding(EGVB)represents a severe complication among patients with cirrhosis and often culminates in fatal outcomes.Interven-tional therapy,a rapidly developing treatment modality over the past few years,has found widespread application in clinical practice due to its minimally inva-sive characteristics.However,whether transjugular intrahepatic portosystemic shunt(TIPS)treatment has an impact on patient prognosis remains controversial.METHODS A retrospective study was conducted on ninety-two patients presenting with cirrhotic EGVB who were admitted to our hospital between September 2020 and September 2022.Based on the different modes of treatment,the patients were assigned to the study group(TIPS received,n=50)or the control group(per-cutaneous transhepatic varices embolization received,n=42).Comparative ana-lyses were performed between the two groups preoperatively and one month postoperatively for the following parameters:Varicosity status;hemodynamic parameters[portal vein flow velocity(PVV)and portal vein diameter(PVD);platelet count(PLT);red blood cell count;white blood cell count(WBC);and hepatic function[albumin(ALB),total bilirubin(TBIL),and aspartate transaminase(AST)].The Generic Quality of Life Inventory-74 was utilized to assess quality of life in the two groups,and the 1-year postoperative rebleeding and survival rates were compared.RESULTS Following surgical intervention,there was an improvement in the incidence of varicosity compared to the preoperative status in both cohorts.Notably,the study group exhibited more pronounced enhancements than did the control group(P<0.05).PVV increased,and PVD decreased compared to the preoperative values,with the study cohort achieving better outcomes(P<0.05).PLT and WBC counts were elevated postoperatively in the two groups,with the study cohort displaying higher PLT and WBC counts(P<0.05).No differences were detected between the two groups in terms of serum ALB,TBIL,or AST levels either preoperatively or postoperatively(P<0.05).Postoperative scores across all dimensions of life quality surpassed preoperative scores,with the study cohort achieving higher scores(P<0.05).At 22.00%,the one-year postoperative rebleeding rate in the study cohort was significantly lower than that in the control group(42.86%;P<0.05);conversely,no marked difference was obser-ved in the 1-year postoperative survival rate between the two cohorts(P>0.05).CONCLUSION TIPS,which has demonstrated robust efficacy in managing cirrhotic EGVB,remarkably alleviates varicosity and improves hemodynamics in patients.This intervention not only results in a safer profile but also contributes significantly to a more favorable prognosis.

Clinical-radiomics nomogram for predicting esophagogastric variceal bleeding risk noninvasively in patients with cirrhosis

BACKGROUND Esophagogastric variceal bleeding(EGVB)is a serious complication of patients with decompensated cirrhosis and is associated with high mortality and morbidity.Early diagnosis and screening of cirrhotic patients at risk for EGVB is crucial.Currently,there is a lack of noninvasive predictive models widely available in clinical practice.AIM To develop a nomogram based on clinical variables and radiomics to facilitate the noninvasive prediction of EGVB in cirrhotic patients.METHODS A total of 211 cirrhotic patients hospitalized between September 2017 and December 2021 were included in this retrospective study.Patients were divided into training(n=149)and validation(n=62)groups at a 7:3 ratio.Participants underwent three-phase computed tomography(CT)scans before endoscopy,and radiomic features were extracted from portal venous phase CT images.The independent sample t-test and least absolute shrinkage and selection operator logistic regression were used to screen out the best features and establish a radiomics signature(RadScore).Univariate and multivariate analyses were performed to determine the independent predictors of EGVB in clinical settings.A noninvasive predictive nomogram for the risk of EGVB was built using independent clinical predictors and RadScore.Receiver operating characteristic,calibration,clinical decision,and clinical impact curves were applied to evaluate the model’s performance.RESULTS Albumin(P=0.001),fibrinogen(P=0.001),portal vein thrombosis(P=0.002),aspartate aminotransferase(P=0.001),and spleen thickness(P=0.025)were selected as independent clinical predictors of EGVB.RadScore,constructed with five CT features of the liver region and three of the spleen regions,performed well in training(area under the receiver operating characteristic curve(AUC)=0.817)as well as in validation(AUC=0.741)cohorts.There was excellent predictive performance in both the training and validation cohorts for the clinical-radiomics model(AUC=0.925 and 0.912,respectively).Compared with the existing noninvasive models such as ratio of aspartate aminotransferase to platelets and Fibrosis-4 scores,our combined model had better predictive accuracy with the Delong's test less than 0.05.The Nomogram had a good fit in the calibration curve(P>0.05),and the clinical decision curve further supported its clinical utility.CONCLUSION We designed and validated a clinical-radiomics nomogram able to noninvasively predict whether cirrhotic patients will develop EGVB,thus facilitating early diagnosis and treatment.

Biopsy forceps are useful for measuring esophageal varices in vitro

BACKGROUND To avoid acute variceal bleeding in cirrhosis,current guidelines recommend screening for high-risk esophageal varices(EVs)by determining variceal size and identifying red wale markings.However,visual measurements of EV during routine endoscopy are often inaccurate.AIM To determine whether biopsy forceps(BF)could be used as a reference to improve the accuracy of binary classification of variceal size.METHODS An in vitro self-made EV model with sizes ranging from 2 to 12 mm in diameter was constructed.An online image-based survey comprising 11 endoscopic images of simulated EV without BF and 11 endoscopic images of EV with BF was assembled and sent to 84 endoscopists.The endoscopists were blinded to the actual EV size and evaluated the 22 images in random order.RESULTS The respondents included 48 academic and four private endoscopists.The accuracy of EV size estimation was low in both the visual(13.81%)and BF-based(20.28%)groups.The use of open forceps improved the ability of the endoscopists to correctly classify the varices by size(small≤5 mm,large>5 mm)from 71.85%to 82.17%(P<0.001).CONCLUSION BF may improve the accuracy of EV size assessment,and its use in clinical practice should be investigated.

Non-invasive assessment of esophageal varices:Status of today

With increasing burden of compensated cirrhosis,we desperately need noninvasive methods for assessment of clinically significant portal hypertension.The use of liver and spleen stiffness measurement helps in deferring unnecessary endoscopies for low risk esophageal varices.This would reduce cost and patient discomfort.However,these special techniques may not be feasible at remote areas where still we need only biochemical parameters.More prospective studies validating the non-invasive risk prediction models are definitely needed.

Non-invasive model for predicting high-risk esophageal varices based on liver and spleen stiffness

BACKGROUND Acute bleeding due to esophageal varices(EVs)is a life-threatening complication in patients with cirrhosis.The diagnosis of EVs is mainly through upper gastrointestinal endoscopy,but the discomfort,contraindications and complications of gastrointestinal endoscopic screening reduce patient compliance.According to the bleeding risk of EVs,the Baveno VI consensus divides varices into high bleeding risk EVs(HEVs)and low bleeding risk EVs(LEVs).We sought to identify a non-invasive prediction model based on spleen stiffness measurement(SSM)and liver stiffness measurement(LSM)as an alternative to EVs screening.AIM To develop a safe,simple and non-invasive model to predict HEVs in patients with viral cirrhosis and identify patients who can be exempted from upper gastrointestinal endoscopy.METHODS Data from 200 patients with viral cirrhosis were included in this study,with 140 patients as the modelling group and 60 patients as the external validation group,and the EVs types of patients were determined by upper gastrointestinal endoscopy and the Baveno Ⅵ consensus.Those patients were divided into the HEVs group(66 patients)and the LEVs group(74 patients).The effect of each parameter on HEVs was analyzed by univariate and multivariate analyses,and a noninvasive prediction model was established.Finally,the discrimination ability,calibration ability and clinical efficacy of the new model were verified in the modelling group and the external validation group.RESULTS Univariate and multivariate analyses showed that SSM and LSM were associated with the occurrence of HEVs in patients with viral cirrhosis.On this basis,logistic regression analysis was used to construct a prediction model:Ln[P/(1-P)]=-8.184-0.228×SSM+0.642×LSM.The area under the curve of the new model was 0.965.When the cut-off value was 0.27,the sensitivity,specificity,positive predictive value and negative predictive value of the model for predicting HEVs were 100.00%,82.43%,83.52%,and 100%,respectively.Compared with the four prediction models of liver stiffness-spleen diameter to platelet ratio score,variceal risk index,aspartate aminotransferase to alanine aminotransferase ratio,and Baveno VI,the established model can better predict HEVs in patients with viral cirrhosis.CONCLUSION Based on the SSM and LSM measured by transient elastography,we established a non-invasive prediction model for HEVs.The new model is reliable in predicting HEVs and can be used as an alternative to routine upper gastrointestinal endoscopy screening,which is helpful for clinical decision making.

Acute-on-chronic liver failure is independently associated with higher mortality for cirrhotic patients with acute esophageal variceal hemorrhage:Retrospective cohort study

BACKGROUND Acute esophageal variceal hemorrhage(AEVH)is a common complication of cirrhosis and might precipitate multi-organ failure,causing acute-on-chronic liver failure(ACLF).AIM To analyze if the presence and grading of ACLF as defined by European Society for the Study of the Liver-Chronic Liver Failure(EASL-CLIF)is able to predict mortality in cirrhotic patients presenting AEVH.METHODS Retrospective cohort study executed in Hospital Geral de Caxias do Sul.Data from medical records from 2010 to 2016 were obtained by searching the hospital electronic database for patients who received terlipressin.Medical records were reviewed in order to determine the diagnosis of cirrhosis and AEVH,including 97 patients.Kaplan-Meier survival analysis was used for univariate analysis and a stepwise approach to the Cox regression for multivariate analysis.RESULTS All-cause mortality for AEVH patients was 36%,40.2%and 49.4%for 30-,90-and 365-day,respectively.The prevalence of ACLF was 41.3%.Of these,35%grade 1,50%grade 2 and 15%grade 3.In multivariate analysis,the non-use of non-selective beta-blockers,presence and higher grading of ACLF and higher Model for End-Stage Liver Disease scores were independently associated with higher mortality for 30-day with the addition of higher Child-Pugh scores for 90-day period.CONCLUSION Presence and grading of ACLF according to the EASL-CLIF criteria was independently associated with higher 30-and 90-day mortality in cirrhotic patients admitted due to AEVH.

Correlation of Platelet Count with Grading of Esophageal Varices in Cirrhotic Patients

Background/Aims: Cirrhosis represents a late stage of progressive hepatic fibrosis and is generally considered to be irreversible in its advanced stages. Esophageal varix is a complication of liver cirrhosis and is the consequence of portal hypertension. The aim of this study was to determine the correlation between the severity of thrombocytopenia and the presenting of esophageal varices (EVs) in cirrhotic patient. Patients and Methods: This study was a retrospective, descriptive, analytic and monocentric study, which was carried out at Gastroenterology Department, Khmer Soviet Friendship Hospital, Phnom Penh, Cambodia. It was conducted from 1st September 2020 to 31st January 2021. All patients were diagnosed as liver cirrhosis by clinic, biology and ultrasound. Patients’ data were noted in standardized questionnaire with information such as age, sex, address, laboratory result, and the result of endoscopic finding. All data were registered into a data set and then analyzed by SPSS program version 23. Results: 1445 patients were enrolled for gastroscopy. Only 303 patients (21%) were suggested for variceal screening after the exclusions. Male was predominant with sex ratio F/M (1/2.03). Patients’ age varied between 21 and 80 years old, with the mean age of 55 ± 11 years old. 199 patients (66%) were found with EVs, while EVs grade 1 and 2 without red signs were predominated, accounting to 22.8% and 19.5% respectively. The majority of the patients with platelet count between 50 - 99 giga/l had EVs vs platelet count > 150 giga/l had no EVs (p Conclusion: Thrombocytopenia is a non-invasive parameter with high accuracy for the prediction of EVs in cirrhosis. The severity of thrombocytopenia increased as the grading of EVs increased. Thus, it can assist in triaging cirrhotic patients for endoscopy to identify EVs.

Letter to editor‘Non-invasive model for predicting high-risk esophageal varices based on liver and spleen stiffness’

predicting high-risk esophageal varices based on liver and spleen stiffness".Acute bleeding caused by esophageal varices is a life-threatening complication in patients with liver cirrhosis.Due to the discomfort,contraindications,and associated complications of upper gastrointestinal endoscopy screening,it is crucial to identify an imaging-based non-invasive model for predicting high-risk esophageal varices in patients with cirrhosis.

Diagnostic accuracy of transient elastography (Fibro Scan) in detection of esophageal varices in patients with cirrhosis: A meta-analysis

AIM To investigate the diagnostic accuracy of Fibro Scan(FS) in detecting esophageal varices(EV) in cirrhotic patients.METHODS Through a systemic literature search of multiple databases, we reviewed 15 studies using endoscopy as a reference standard, with the data necessary to calculate pooled sensitivity(SEN) and specificity(SPE), positive and negative LR, diagnostic odds ratio(DOR) and area under receiver operating characteristics(AUROC). The quality of the studies was rated by the Quality Assessment of Diagnostic Accuracy studies-2 tool. Clinical utility of FS for EV was evaluated by a Fagan plot. Heterogeneity was explored using meta-regression and subgroup analysis. All statistical analyses were conducted via Stata12.0, MetaD isc1.4 and RevM an5.RESULTS In 15 studies(n = 2697), FS detected the presence of EV with the summary sensitivities of 84%(95%CI: 81.0%-86.0%), specificities of 62%(95%CI: 58.0%-66.0%), a positive LR of 2.3(95%CI: 1.81-2.94), a negative LR of 0.26(95%CI: 0.19-0.35), a DOR of 9.33(95%CI: 5.84-14.92) and an AUROC of 0.8262. FS diagnosed the presence of large EV with the pooled SEN of 0.78(95%CI: 75.0%-81.0%), SPE of 0.76(95%CI: 73.0%-78.0%), a positive and negative LR of 3.03(95%CI: 2.38-3.86) and 0.30(95%CI: 0.23-0.39) respectively, a summary diagnostic OR of 10.69(95%CI: 6.81-16.78), and an AUROC of 0.8321. A meta-regression and subgroup analysis indicated different etiology could serve as a potential source of heterogeneity in the diagnosis of the presence of EV group. A Deek's funnel plot suggested a low probability for publication bias.CONCLUSION Using FS to measure liver stiffness cannot provide high accuracy for the size of EV due to the various cutoff and different etiologies. These limitations preclude widespread use in clinical practice at this time; therefore, the results should be interpreted cautiously given its SEN and SPE.

Urinary Vascular Endothelial Growth Factor (VEGF) as a Novel Marker for Early Prediction of Esophageal Varices in Patients with Chronic Liver Disease

Background/Aims: Vascular Endothelial Growth Factor (VEGF) has a crucial role in portal hypertension and collateral vessels formation. This study aims to assess urinary VEGF in cirrhotic patients as a predictor of presence of esophageal varices, and variceal bleeding. Settings and Design: 42 cirrhotic patients were randomly selected and classified into 2 groups according to the presence of variceal bleeding. Methods and Material: Urinary VEGF was measured and corrected against urinary creatinine. Platelet count, liver functions, abdominal ultrasonography and upper endoscopy were done. Statistical Analysis Used: Comparison was done by Mann Whitney and Kruskal Wallis tests. Correlation was done using Spearman rank correlation. Multivariable logistic regression was done to identify predictors of variceal bleeding and presence of large varices. Receiver operator characteristic curve (ROC) analysis was used to determine the optimum cut off value of predictors. Results and Conclusions: Urinary VEGF was lower in cirrhotic patients with esophageal varices than those without. Low VEGF, low platelet count and splenomegaly were found to be independent predictors of both the presence of large esophageal varices, and variceal bleeding. Cut-off values for platelet count ≤ 166.3 × 103/μL, and corrected VEGF ≤ 59.12 pg/mg were predictive of large esophageal varices with 93.1%, 86.2% sensitivity and 74.5%, 58.2% specificity respectively. While variceal bleeding could be predicted at a platelet count ≤ 153 × 103/μL, and corrected VEGF ≤ 45.08 pg/mg with 90.9%, 81.8% sensitivity and 72.6%, 59.7% specificity respectively. The study concludes that urinary VEGF can be used as an alternative to upper endoscopic screening.

Antiviral therapy delays esophageal variceal bleeding in hepatitis B virus-related cirrhosis

AIM:To investigate the effect of antiviral therapy with nucleoside analogs in hepatitis B virus(HBV)-related cirrhosis and esophageal varices.METHODS:Eligible patients with HBV-related cirrhosis and esophageal varices who consulted two tertiary hospitals in Beijing,China,the Chinese Second Artillery General Hospital and Chinese PLA General Hospital,were enrolled in the study from January 2005 to December 2009. Of 117 patients,79 received treatment with different nucleoside analogs and 38 served as controls. Bleeding rate,change in variceal grade and non-bleeding duration were analyzed. Multivariate Cox proportional hazard regression was used to identify factors related to esophageal variceal bleeding.antiviral group compared to the control group(29.1%vs 65.8%,P < 0.001). Antiviral therapy was an independent factor related to esophageal bleeding in multivariate analysis(HR = 11.3,P < 0.001). The mean increase in variceal grade per year was lower in the antiviral group(1.0 ± 1.3 vs 1.7 ± 1.2,P = 0.003). Nonbleeding duration in the antiviral group was prolonged in the Kaplan-Meier model. Viral load rebound was observed in 3 cases in the lamivudine group and in 1 case in the adefovir group,all of whom experienced bleeding. Entecavir and adefovir resulted in lower bleeding rates(17.2% and 28.6%,respectively) than the control(P < 0.001 and P = 0.006,respectively),whereas lamivudine(53.3%) did not(P = 0.531).CONCLUSION:Antiviral therapy delays the progression of esophageal varices and reduces bleeding risk in HBV-related cirrhosis,however,high-resistance agents tend to be ineffective for long-term treatment.

Computed tomography vs liver stiffness measurement and magnetic resonance imaging in evaluating esophageal varices in cirrhotic patients:A systematic review and meta-analysis

BACKGROUND Computed tomography(CT),liver stiffness measurement(LSM),and magnetic resonance imaging(MRI)are non-invasive diagnostic methods for esophageal varices(EV)and for the prediction of high-bleeding-risk EV(HREV)in cirrhotic patients.However,the clinical use of these methods is controversial.AIM To evaluate the accuracy of LSM,CT,and MRI in diagnosing EV and predicting HREV in cirrhotic patients.METHODS We performed literature searches in multiple databases,including Pub Med,Embase,Cochrane,CNKI,and Wanfang databases,for articles that evaluated the accuracy of LSM,CT,and MRI as candidates for the diagnosis of EV and prediction of HREV in cirrhotic patients.Summary sensitivity and specificity,positive likelihood ratio and negative likelihood ratio,diagnostic odds ratio,and the areas under the summary receiver operating characteristic curves were analyzed.The quality of the articles was assessed using the quality assessment of diagnostic accuracy studies-2 tool.Heterogeneity was examined by Q-statistic test and I2 index,and sources of heterogeneity were explored using metaregression and subgroup analysis.Publication bias was evaluated using Deek’s funnel plot.All statistical analyses were conducted using Stata12.0,Meta Disc1.4,and Rev Man5.3.RESULTS Overall,18,17,and 7 relevant articles on the accuracy of LSM,CT,and MRI in evaluating EV and HREV were retrieved.A significant heterogeneity was observed in all analyses(P<0.05).The areas under the summary receiver operating characteristic curves of LSM,CT,and MRI in diagnosing EV and predicting HREV were 0.86(95%confidence interval[CI]:0.83-0.89),0.91(95%CI:0.88-0.93),and 0.86(95%CI:0.83-0.89),and 0.85(95%CI:0.81-0.88),0.94(95%CI:0.91-0.96),and 0.83(95%CI:0.79-0.86),respectively,with sensitivities of 0.84(95%CI:0.78-0.89),0.91(95%CI:0.87-0.94),and 0.81(95%CI:0.76-0.86),and 0.81(95%CI:0.75-0.86),0.88(95%CI:0.82-0.92),and 0.80(95%CI:0.72-0.86),and specificities of 0.71(95%CI:0.60-0.80),0.75(95%CI:0.68-0.82),and 0.82(95%CI:0.70-0.89),and 0.73(95%CI:0.66-0.80),0.87(95%CI:0.81-0.92),and 0.72(95%CI:0.62-0.80),respectively.The corresponding positive likelihood ratios were 2.91,3.67,and 4.44,and 3.04,6.90,and2.83;the negative likelihood ratios were 0.22,0.12,and 0.23,and 0.26,0.14,and 0.28;the diagnostic odds ratios were 13.01,30.98,and 19.58,and 11.93,49.99,and 10.00.CT scanner is the source of heterogeneity.There was no significant difference in diagnostic threshold effects(P>0.05)or publication bias(P>0.05).CONCLUSION Based on the meta-analysis of observational studies,it is suggested that CT imaging,a non-invasive diagnostic method,is the best choice for the diagnosis of EV and prediction of HREV in cirrhotic patients compared with LSM and MRI.

Gastroesophageal reflux in cirrhotic patients without esophageal varices

AIM: To evaluate the esophageal motility and abnormal acid and bile reflux incidence in cirrhotic patients without esophageal varices (EV). METHODS: Seventy-eight patients with liver cirrhosis without EV confirmed by upper gastroesophageal endoscopy and 30 healthy control volunteers were prospectively enrolled in this study. All the patients were evaluated using a modified protocol including Child-Pugh score, upper gastrointestinal endoscopy, esophageal manometry, simultaneous ambulatory 24-h esophageal pH and bilirubin monitoring. All the patients and volunteers accepted the manometric study. RESULTS: In the liver cirrhosis group, lower esophageal sphincter pressure (LESP, 15.32 ± 2.91 mmHg), peristaltic amplitude (PA, 61.41 ± 10.52 mmHg), peristaltic duration (PD, 5.32 ± 1.22 s), and peristaltic velocity (PV, 5.22 ± 1.11 cm/s) were all significantly abnormal in comparison with those in the control group (P < 0.05), and LESP was negatively correlated with Child-Pugh score. The incidence of reflux esophagitis (RE) and pathologic reflux was 37.18% and 55.13%, respectively(vs control, P < 0.05). And the incidence of isolated abnormal acid reflux, bile reflux and mixed reflux was 12.82%, 14.10% and 28.21% in patients with liver cirrhosis without EV. CONCLUSION: Cirrhotic patients without EV presented esophageal motor disorders and mixed acid and bile reflux was the main pattern; the cirrhosis itself was an important causative factor.

Cost-effectiveness analysis of beta-blockers vs endoscopic surveillance in patients with cirrhosis and small varices

AIM: To evaluate the most cost-effectiveness strategy for preventing variceal growth and bleeding in patients with cirrhosis and small esophageal varices.

Presence of columnar-lined esophagus is negatively associated with the presence of esophageal varices in Japanese alcoholic men

AIM To determine whether the presence of columnar-lined esophagus(CLE) is associated with the presence of esophageal varices(EVs) in male Japanese alcoholics. METHODS The subjects were 1614 Japanese alcohol-dependent men(≥ 40 years of age) who had undergone upper gastrointestinal endoscopic screening. Digitalized records of high-quality endoscopic images that included the squamocolumnar junction and esophagogastric junction were retrospectively jointly reviewed by four expert endoscopists for the purpose of diagnosing CLE. The authors investigated whether and to what extent there were associations between the presence of CLE and the presence of EVs, especially in the group with liver cirrhosis(LC).RESULTS CLE ≥ 5 mm in length was found in 355 subjects(≥ 30 mm in 6 of them), LC without EVs in 152 subjects, LC with EVs in 174 subjects, and EVs without LC in 6 subjects. Advanced EVs, i.e., nodular, large or coiled forms, red color sign, or post-treatment, were found in 88 subjects. The incidence of CLE ≥ 5 mm decreased in the following order(P < 0.0001): 23.3% in the group without EVs, 17.4% in the group with small and straight EVs, and 5.7% in the group with advanced EVs. The multivariate ORs(95%CI) for EVs and advanced EVs in the group with LC were lower when CLE ≥ 5 mm was present [0.46(0.23-0.93) and 0.24(0.08-0.74), respectively, vs 0-4 mm CLE]. CONCLUSION The presence of CLE in male Japanese alcoholics was negatively associated with the presence of EVs.