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.

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.

Characterization of the Gastric Mucosal Microbiota in Patients with Liver Cirrhosis and Its Associations with Gastrointestinal Symptoms

Several studies have indicated that the oral and gut microbiota may exhibit differences in patients with cirrhosis.Less is known about the microbiota in the stomach,which is located between the oral cavity and the intestinal tract.In this study,the gastric mucosal microbiota of patients with liver cirrhosis and controls were analyzed with 16S ribosomal RNA(rRNA)pyrosequencing.Cirrhotic patients had significantly lower Helicobacter pylori(H.pylori)infection rates,as confirmed by both the histological method and the pyrosequencing method.In H.pylori-negative subjects,gastric bacterial communities of healthy and cirrhosis cohorts were clustered into four clusters based on bacterial compositions:Cluster_1 and Cluster_2(mostly cirrhosis),Cluster_3(mostly healthy),and Cluster_4(around half of each).Compositional and functional differences were observed among these different clusters.At the genus level,Cluster_1 and Cluster_2 showed enrichment of Neisseria and Streptococcus,respectively.Functionally,Cluster_2 was characterized as depleted of genetic information processing,as well as of modules related to glycan biosynthesis and metabolism.Patients in Cluster_2 had more severe gastrointestinal symptoms and a higher rate of previous endoscopic variceal ligation(EVL)therapy than patients in other clusters.Our findings suggest that the colonization of both H.pylori and non-H.pylori is influenced in liver cirrhosis.Although the H.pylori-negative gastric mucosal microbiota showed considerable heterogeneity,associations between specific gastric microbiota and clinical characteristics could be observed.Previous EVL therapy might lead to a distinct structure of the gastric mucosal microbiota,thus aggravating the gastrointestinal symptoms in H.pylori-negative cirrhotic patients.

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.

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.

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.

Prognosis of hepatic cirrhosis patients with esophageal or gastric variceal hemorrhage: multivariate analysis

Objective: To study the effect of bacterial infection, use of antibiotics, active bleeding at endoscopy, and the severity of liver disease as prognostic factors in hepatic cirrhotic patients during the first 5 days after the episode of esophageal or gastric variceal hemor- rhage. Methods: Seventy-six hepatic cirrhosis patients with esophageal or gastric variceal bleeding were enrolled. Bleeding was managed in a standardized protocol u- sing octreotide and vasopressin in sclerotherapy or band ligation for active bleeding at endoscopy. The screening protocol for bacterial infection consisted of chest radiograph; blood, urine and ascitic fluid cul- tures; the severity of liver disease shown by Child- Pugh score. Results: Active bleeding was observed at endoscopy in 40 patients (53%). Failure to control bleeding Within 5 days occurred in 36 patients (45%). Empir- ical antibiotic treatment was used in 53 patients (67%), whereas bacterial infections were documen- ted in 43 patients (57%). Multivariate analysis showed that proven bacterial infection (P<0.01) or antibiotic use (P<0.05) as well as active bleeding at endoscopy (P<0.01) and Child-Pugh score (P< 0.01) were independent prognostic factors of failure to control bleeding. Conclusion: Bacterial infection is associated with fai- lure to control esophageal or gastric variceal bleeding in hepatic cirrhotic patients.

Non-invasive model for predicting esophageal varices based on liver and spleen volume

BACKGROUND Upper endoscopy is the gold standard for predicting esophageal varices in China.Guidelines and consensus suggest that patients with liver cirrhosis should undergo periodic upper endoscopy,most patients undergo their first upper endoscopy when esophageal variceal bleeds.Therefore,it is important to develop a non-invasive model to early diagnose esophageal varices.AIM To develop a non-invasive predictive model for esophageal varices based on liver and spleen volume in viral cirrhosis patients.METHODS We conducted a cross-sectional study based on viral cirrhosis crowd in the Second Affiliated Hospital of Xi'an Jiaotong University.By collecting the basic information and clinical data of the participants,we derived the independent risk factors and established the prediction model of esophageal varices.The established model was compared with other models.Area under the receiver operating characteristic curve,calibration plot and decision curve analysis were used to test the discriminating ability,calibration ability and clinical practicability in both the internal and external validation.RESULTS The portal vein diameter,the liver and spleen volume,and volume change rate were the independent risk factors of esophageal varices.We successfully used the factors to establish the predictive model[area under the curve(AUC)0.87,95%CI:0.80-0.95],which showed better predictive value than other models.The model showed good discriminating ability,calibration ability and the clinical practicability in both modelling group and external validation group.CONCLUSION The developed non-invasive predictive model can be used as an effective tool for predicting esophageal varices in viral cirrhosis patients.

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.

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.

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.

Comparison of hepatic venous pressure gradient and endoscopic grading of esophageal varices

AIM: To determine the correlation between the hepatic venous pressure gradient and the endoscopic grade of esophageal varices.METHODS: From September 2009 to March 2013, a total of 176 measurements of hepatic venous pressure gradient (HVPG) were done in 146 patients. Each transjugular HVPG was measured twice, first using an end whole catheter (EH-HVPG), and then using a balloon catheter (B-HVPG). The HVPG was compared with the endoscopic grade of esophageal varices (according to the general rules for recording endoscopic findings of esophagogastric varices), which was recorded within a month of the measurement of HVPG.RESULTS: The study included 110 men and 36 women, with a mean age of 56.1 years (range, 43-76 years). The technical success rate of the pressure measurements was 100% and there were no complication related to the procedures. Mean HVPG was 15.3 mmHg as measured using the end hole catheter method and 16.5 mmHg as measured using the balloon catheter method. Mean HVPG (both EH-HVPG and B-HVPG) was not significantly different among patients with different characteristics, including sex and comorbid factors, except for cases with hepatocellular carcinoma (B-HVPG, P = 0.01; EH-HVPG, P = 0.02). Portal hypertension (&#x0003e; 12 mmHg HVPG) occurred in 66% of patients according to EH-HVPG and 83% of patients according to B-HVGP, and significantly correlated with Child&#x02019;s status (B-HVPG, P &#x0003c; 0.000; EH-HVGP, P &#x0003c; 0.000) and esophageal varies observed upon endoscopy (EH-HVGP, P = 0.003; B-HVGP, P = 0.006). One hundred and thirty-five endoscopies were performed, of which 15 showed normal findings, 27 showed grade 1 endoscopic esophageal varices, 49 showed grade 2 varices, and 44 showed grade 3 varices. When comparing endoscopic esophageal variceal grades and HVPG using univariate analysis, the P value was 0.004 for EH-HVPG and 0.002 for B-HVPG.CONCLUSION: Both EH-HVPG and B-HVPG showed a positive correlation with the endoscopic grade of esophageal varices, with B-HVPG showing a stronger correlation than EH-HVPG.

Percutaneous transsplenic embolization of esophageal and gastrio-fundal varices in 18 patients

AIM: Clinical application and potential complication of percutaneous transsplenic varices embolization (PTSVE) of esophageal or gastrio-fundal varices in patients with hepatocellular carcinoma (HCC) complicated with portal vein cancerous thrombosis (PVCT).METHODS: 18 patients with HCC complicated with PVCT and esophageal or gastrio-fundal varices who underwent PTSVE were collected. The rate of success, complication, mortality of the procedure and postoperative complication were recorded and analyzed.RESULTS: PTSVE were successfully performed in 16 of 18cases, and the rate of success was 89%. After therapy erythrocyte counts decreased in all of the natunts. 5 of patients needed blood transfusion, 2 patients requiredsurgical intervention because of and 11 patients with ascites were alleviated by diuresis. Among these 18patients, the procedure-related mortality was 11% (2/18),one died of acute hepatic failure on the forth day after procedure, another died of acute renal failure on the fifth day. The patients were follow up for 112 mon exceptone. 13of them died of their tumors but none of them experienced variceal bleeding.CONCLUSION: PTSVE is a relatively safe and effective method to treat esophageal or gastrio-fundal varices in HCCpatients with PVCT when percutaneous transhepatic varices embolization (PTHVE) of varices is impossible.

Liver stiffness and serum markers for excluding high-risk varices in patients who do not meet Baveno VI criteria

BACKGROUND The Baveno VI criteria for predicting esophageal varices, i.e., liver stiffness measurement (LSM)< 20 kPa and platelet (PLT) count > 150 × 109/L, identify patients who can safely avoid gastroscopy screening. However, they require further refinement. AIM To evaluate the utility of LSM and serum markers of liver fibrosis in ruling out high-risk varices (HRV) in patients who do not meet Baveno VI criteria. METHODS Data from 132 patients with hepatitis B virus (HBV)-related compensated liver cirrhosis who did not meet the Baveno VI criteria were retrospectively reviewed. MedCalc 15.8 was used to calculate receiver operating characteristic (ROC) curves, and the accuracy of LSM, PLT count, aspartate aminotransferase (AST)- to-PLT ratio index, Fibrosis-4, and the Lok index in predicting HRV were evaluated according to the area under each ROC curve (AUROC). The utility of LSM, PLT, and serum markers of liver fibrosis stratified by alanine transaminase (ALT) and total bilirubin (TBil) levels was evaluated for ruling out HRV. RESULTS In all patients who did not meet the Baveno VI criteria, the independent risk factors for HRV were LSM and ALT. Only the AUROC of Lok index was above 0.7 for predicting HRV, and at a cutoff value of 0.4531 it could further spare 24.2% of gastroscopies without missing HRVs. The prevalence of HRV was significantly lower in patients with ALT or TBil ≥ 2 upper limit of normal (ULN)(14.3%) than in patients with both ALT and TBil < 2 ULN (34.1%)(P = 0.018). In the 41 patients with ALT and TBil < 2 ULN, LSM had an AUROC for predicting HRV of 0.821. LSM < 20.6 kPa spared 39.0% of gastroscopies without missing HRVs. In the 91 patients with ALT or TBiL ≥ 2 ULN, the Lok index and PLT had AUROCs of 0.814 and 0.741, respectively. Lok index ≤ 0.5596 or PLT > 100 × 109/L further spared 39.6% and 43.9% of gastroscopies, respectively, without missing HRVs. CONCLUSION In HBV-related compensated cirrhosis patients who do not meet Baveno VI criteria, the LSM, PLT, or Lok index cutoff stratified by ALT and TBil accurately identifies more patients without HRV.

Proton pump inhibitor use increases mortality and hepatic decompensation in liver cirrhosis

BACKGROUND Proton pump inhibitors(PPIs)are widely prescribed,often without clear indications.There are conflicting data on its association with mortality risk and hepatic decompensation in cirrhotic patients.Furthermore,PPI users and PPI exposure in some studies have been poorly defined with many confounding factors.AIM To examine if PPI use increases mortality and hepatic decompensation and the impact of cumulative PPI dose exposure.METHODS Data from patients with decompensated liver cirrhosis were extracted from a hospital database between 2013 to 2017.PPI users were defined as cumulative defined daily dose(cDDD)≥28 within a landmark period,after hospitalisation for hepatic decompensation.Cox regression analysis for comparison was done after propensity score adjustment.Further risk of hepatic decompensation was analysed by Poisson regression.RESULTS Among 295 decompensated cirrhosis patients,238 were PPI users and 57 were non-users.PPI users had higher mortality compared to non-users[adjusted HR=2.10,(1.20-3.67);P=0.009].Longer PPI use with cDDD>90 was associated with higher mortality,compared to non-users[aHR=2.27,(1.10-5.14);P=0.038].PPI users had a higher incidence of hospitalization for hepatic decompensation[aRR=1.61,(1.30-2.11);P<0.001].CONCLUSION PPI use in decompensated cirrhosis is associated with increased risk of mortality and hepatic decompensation.Longer PPI exposure with cDDD>90 increases the risk of mortality.

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.

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.

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.

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.