Presence Of High-risk Varices Research Articles

The Role of Shear-Wave Elastography of the Spleen in Ruling out the Presence of High-Risk Varices in Non-Alcoholic Fatty Liver Disease (NAFLD)

The progression of liver fibrosis and the presence of portal hypertension are two key points in the follow-up and severity assessment of patients with chronic liver disease. Objective evaluation of such aspects has proven to be difficult due to the lack of reproducible and standardized non-invasive methods. Therefore, the aim of this study was to evaluate whether spleen stiffness (SS) can rule out the presence of high-risk varices (HRVs) in patients with non-alcoholic fatty liver disease (NAFLD). We designed a prospective follow-up of a cohort of 48 consecutive patients diagnosed with compensated advanced chronic liver disease (cACLD) due to NAFLD, between January 2020 and January 2021. After clinical evaluation, laboratory testing, ultrasonography (US), and shear-wave elastography (2D-SWE.GE) of both the liver and the spleen, patients were endoscopically screened for esophageal varices, gastric varices, and portal hypertensive gastropathy. Correlations and predictors were assessed. After univariate, multivariate, and predictive analyses, SS could be referred to as an independent predictor for high-risk varices (AUROC 0.987, p < 0.001, OR 4.985, 95% CI: 1.57–15.73, p = 0.006), with a calculated cutoff value of 17.95 kPa. These results are consistent with those of other, similar studies using both 2D-SWE.GE and a similar module (2D-SWE.SSI) in patients with metabolic liver disease. When confirmed by subsequent larger studies, SS could potentially become a useful non-invasive tool in the assessment of clinically significant portal hypertension in patients with advanced fatty liver disease.

Risk of Variceal Bleeding in Patients With Advanced Hepatocellular Carcinoma Receiving Atezolizumab/Bevacizumab

Risk of Variceal Bleeding in Patients With Advanced Hepatocellular Carcinoma Receiving Atezolizumab/Bevacizumab

Variceal bleeding is aggravated by portal venous invasion of hepatocellular carcinoma: a matched nested case-control study

BackgroundWe hypothesized that portal vein tumor thrombosis (PVTT) in hepatocellular carcinoma (HCC) increases portal pressure and causes esophageal varices and variceal bleedings. We examined the incidence of high-risk varices and variceal bleeding and determined the indications for variceal screening and prophylaxis.MethodsThis study included 1709 asymptomatic patients without any prior history of variceal hemorrhage or endoscopic prophylaxis who underwent upper endoscopy within 30 days before or after initial anti-HCC treatment. Of these patients, 206 had PVTT, and after 1:2 individual matching, 161 of them were matched with 309 patients without PVTT. High-risk varices were defined as large/medium varices or small varices with red-color signs and variceal bleeding. Bleeding rates from the varices were compared between matched pairs. Risk factors for variceal bleeding in the entire set of patients with PVTT were also explored.ResultsIn the matched-pair analysis, the proportion of high-risk varices at screening (23.0% vs. 13.3%; P = 0.003) and the cumulative rate of variceal bleeding (4.5% vs. 0.4% at 1 year; P = 0.009) were significantly greater in the PVTT group. Prolonged prothrombin time, lower platelet count, presence of extrahepatic metastasis, and Vp4 PVTT were independent risk factors related to high-risk varices in the total set of 206 patients with PVTT (Adjusted odds ratios [95% CIs], 1.662 [1.151–2.401]; 0.985 [0.978–0.993]; 4.240 [1.783–10.084]; and 3.345 [1.457–7.680], respectively; Ps < 0.05). During a median follow-up of 43.2 months, 10 patients with PVTT experienced variceal bleeding episodes, 9 of whom (90%) had high-risk varices. Presence of high-risk varices and sorafenib use for HCC treatment were significant predictors of variceal bleeding in the complete set of patients with PVTT (Adjusted hazard ratios [95% CIs], 26.432 [3.230–216.289]; and 5.676 [1.273–25.300], respectively; Ps < 0.05).ConclusionsPVTT in HCC appears to increase the likelihood of high-risk varices and variceal bleeding. In HCC patients with PVTT, endoscopic prevention could be considered, at least in high-risk variceal carriers taking sorafenib.

Diagnostic Accuracy of Non-invasive Laboratory-Based Fibrosis Scores in Predicting the Presence of Esophageal Varices in Liver Cirrhosis

Introduction: Non-invasive assessment of esophageal varices (EVs) may reduce endoscopic burden and cost. This study aimed to evaluate the diagnostic accuracy of non-invasive fibrosis scores (AAR, APRI, FIB-4, King and Lok scores) for the prediction of varices in liver cirrhosis.&#x0D; Methods: This prospective study included 100 liver cirrhosis patients who underwent screening endoscopy for EVs. AAR, APRI, FIB-4, King and Lok scores were assessed. The receiver operating characteristic curves (ROC) were plotted to measure and compare the performance of each score for predicting EVs and to obtain the corresponding optimal prediction value.&#x0D; Results: Of the 100 patients, 70 were males and 30 were females with a mean age of 54.05±11.58 years. Esophageal varices were found in 77 patients out of which 58.44% were high-risk varices. Platelet count and non-invasive fibrosis scores APRI, FIB-4, Lok and King were able to discriminate patients with and without varices. Using area under receiver operating characteristic curve (AUROC), these scores were found to have low to moderate diagnostic accuracy for the presence of EVs and high-risk EVs, where the APRI score had the highest AUROC (0.77 and 0.70) respectively. At a cutoff value &gt; 1.4, APRI score had 90.9% sensitivity, 60.9% specificity and 84 % diagnostic accuracy in predicting the presence of varices, while it had 84.4% sensitivity, 45.5% specificity and 63% diagnostic accuracy in predicting the presence of highrisk varices, at a cutoff value &gt; 2.02.&#x0D; Conclusion: APRI, AAR, FIB-4, King, and Lok scores had low to moderate diagnostic accuracy in predicting the presence of varices in liver cirrhosis. The APRI score can help select a patient for the endoscopy but cannot replace endoscopy for esophageal varices screening.

Accuracy of Fibrosis-4 Index in Identification of Patients with Cirrhosis Who Could Potentially Avoid Variceal Screening Endoscopy.

A potential restriction of the Baveno VI consensus, which helps to avoid unnecessary endoscopies, is the limited availability of FibroScan. We aimed to identify serum fibrosis indices that might aid in ruling out the presence of high-risk varices in cirrhotic patients. This retrospective study included 541 consecutive patients with cirrhosis who underwent endoscopy and had data available for nine serum fibrosis indices, including platelet count, hyaluronic acid, 7S fragment of type 4 collagen, procollagen type III N-terminal peptide, tissue inhibitor of metalloproteinases 1, Mac-2 binding protein glycosylation isomer, fibrosis index based on four factors (FIB-4), aspartate transaminase/platelet ratio index and enhanced liver fibrosis score. Optimal index cutoffs for predicting high-risk varices were calculated in an estimation cohort (n = 127) and evaluated in a validation cohort (n = 351). The diagnostic performance of the indices was assessed by receiver operating characteristic curve analysis. In the estimation cohort, a FIB-4 cutoff of 2.78 provided the greatest diagnostic accuracy in predicting both all-grade and high-risk varices. FIB-4 had a negative predictive value of 1.00 for high-risk varices in both cohorts, and 21.3% (27/127) and 14.8% (52/351) of the estimation and validation cohorts, respectively, avoided esophagogastroduodenoscopy; no high-risk varices were missed in either cohort. FIB-4 correctly identifies the absence of high-risk varices in patients with cirrhosis. Therefore, those with a FIB-4 of ≥2.78 should undergo esophagogastroduodenoscopy, and FIB-4 determination should be recommended every 6–12 months concurrently with the other blood tests until the index value reaches 2.78 in those with a FIB-4 of <2.78.

Contrast-Enhanced CT May Identify High-Risk Esophageal Varices in Patients With Cirrhosis

OBJECTIVE. The Baveno VI consensus established guidelines to reduce unnecessary screening esophagogastroduodenoscopy (EGD) for esophageal varices (EVs). We assessed whether EVs that would require intervention at EGD can be identified on CT and evaluated if recommending EGD on the basis of CT findings would result in unnecessary EGD according to the Baveno VI consensus guidelines. MATERIALS AND METHODS. This single-institution retrospective study identified 97 contrast-enhanced CT examinations within 3 months of EGD in 93 patients with cirrhosis from 2008 to 2018. Demographic information, EGD findings, interventions, and laboratory data were reviewed. CT scans were reviewed for EVs and compared with EGD findings. Var-ices that were 4 mm or larger were considered large, and those requiring intervention were considered high risk. RESULTS. The presence of large EVs on CT was 80% sensitive and 87% specific for high-risk varices at EGD. Large EVs on CT were associated with bleeding as the indication for EGD (p = 0.03) and the presence of high-risk varices at EGD (p < 0.001). The positive predictive value that a large EV on CT corresponded to a high-risk EV at EGD was 90.4% (95% CI, 0.78-0.96). Patients with large EVs on CT were 9.4 times more likely to have a grade III or grade IV EV at EGD. CONCLUSION. Large EVs on CT correlated with high-risk varices at EGD and may be a useful indicator that EGD should be considered for confirmatory diagnosis and treatment. Recommending EGD for patients with EVs of 4 mm or larger did not result in EGD that would be deemed unnecessary according to the Baveno VI consensus guidelines.

Role of Spleen Stiffness Measurement by 2D-Shear Wave Elastography in Ruling Out the Presence of High-Risk Varices in Cirrhotic Patients.

To evaluate if spleen stiffness measurement (SSM) can rule out the presence of high-risk varices in patients with cirrhosis, avoiding an upper gastrointestinal endoscopy (UGE). We enrolled 71 cirrhotic patients irrespective of liver disease's etiology. 2D shear wave elastography (SWE) of spleen and UGE was performed. High-risk varices (HRV) were defined as esophageal varices ≥ 5mm and/or red spots and any gastric varices. Esophageal varices were documented in 37 (52.1%) and HRV in 25 (35.2%) patients. SSM was not technically feasible in 7/71 patients (9.8%). From the remaining 64 patients, when those with cholestatic liver disease were excluded (n = 17), SSM < 35.8kPa was found to exclude well the existence of HRV offering an AUROC of 0.854 (p < 0.001), sensitivity 88.9%, negative predictive value (NPV) 91.3%, specificity 72.4%, and positive predictive value (PPV) 66.7%. Only 2/47 patients (4.3%) were misclassified, and 23 (48.9%) could avoid endoscopy. In the total cohort of 64 patients, SSM < 33.7kPa was found to exclude well the presence of HRV offering AUROC 0.792 (p < 0.001), sensitivity 91.7%, specificity 60%, NPV 92.3%, and PPV 57.9%. The misclassification rate was 3.1% (2/64), while 26/64 (40.6%) could avoid endoscopy. 2D-SWE of spleen is a reliable method for ruling out the presence of HRV in cirrhotic patients. If larger studies confirm our results, a large number of endoscopies could be avoided.

Role and clinical meaning of non-invasive tests in the evaluation of portal hypertension in patients with advanced chronic liver disease

Portal hypertension (PH) is the main driver of complications in patients with advanced chronic liver disease (ACLD). Correctly identifying the presence and severity of PH is crucial for the management and prognosis of compensated ACLD (cACLD) patients. Over the last 20 years, several non-invasive tests (NITs) have been proposed for PH assessment; among these, liver (LSM) and spleen (SSM) stiffness measurement by transient elastography are the most validated and accurate predictors of clinically significant PH (CSPH) and its complications, such as gastroesophageal varices, clinical decompensation and hepatocellular carcinoma. The inclusion of NITs in the official recommendations of the Baveno VI Consensus, as valid and trustworthy tools to assess PH in cACLD patients, represents one of the major advances in hepatology of the last years. For instance, the recently proposed Baveno VI Criteria (LSM<20 kPa and platelet count >150 × 109/L) have proven to be a valid strategy to rule out the presence of high-risk varices (HRV) and identify patients that can safely avoid screening upper endoscopy (EGD). In conclusion, further studies are necessary to fully explore the potential of NITs and maximize their use in everyday clinical practice.

Risk Stratification with Noninvasive Tools in Patients with Compensated Cirrhosis

The main goal of the present review is to summarize current strategies to predict the presence of clinically significant portal hypertension (CSPH), varices, and decompensation with noninvasive methods, mainly focusing in transient elastography (TE) which is the most validated tool. TE has demonstrated to predict the presence of CSPH. Values >20–25 kPa rule in the presence of CSPH with a probability >90%. On the other hand, when combined with platelet count, TE has been shown to rule out the presence of high-risk varices. In fact, patients with compensated advanced chronic liver disease (cACLD) with TE 150 × 109/L have a very low risk of having varices needing treatment and endoscopy can be safely avoided. TE also can predict the risk of decompensation especially when repeated measures are performed. TE is easy to perform in clinical daily practice and it has been incorporated in clinical guidelines for the management of patients with advanced chronic liver disease. Current evidences and future improvements will greatly reduce the use of invasive procedures in cACLD patients.

Measurement of Spleen Stiffness by Acoustic Radiation Force Impulse Imaging Identifies Cirrhotic Patients With Esophageal Varices

We evaluated whether spleen stiffness (SS), measured by acoustic radiation force impulse imaging, can identify patients who have esophageal varices (EVs); those without EVs would not require endoscopic examination. In a prospective study, we measured SS and liver stiffness (LS) in 340 patients with cirrhosis undergoing endoscopic screening for EVs and 16 healthy volunteers (controls) at the Kurashiki Central Hospital in Okayama, Japan. The diagnostic accuracy of SS for the presence of EVs was compared with that of other noninvasive parameters (LS, spleen diameter, and platelet count). Optimal cutoff values of SS were chosen to confidently rule out the presence of varices. Patients with cirrhosis had significantly higher SS and LS values than controls (P < .0001 and P < .0001, respectively). Levels of SS were higher among patients with EVs (n = 132) than controls, and values were highest among patients with high-risk EVs (n = 87). SS had the greatest diagnostic accuracy for the identification of patients with EVs or high-risk EVs compared with other noninvasive parameters, independent of the etiology of cirrhosis. An SS cutoff value of 3.18 m/s identified patients with EVs with a 98.4% negative predictive value, 98.5% sensitivity, 75.0% accuracy, and 0.025 negative likelihood ratio. An SS cutoff value of 3.30 m/s identified patients with high-risk EVs with a 99.4% negative predictive value, 98.9% sensitivity, 72.1% accuracy, and 0.018 negative likelihood ratio. SS values less than 3.3 m/s ruled out the presence of high-risk varices in patients with compensated or decompensated cirrhosis. SS could not be measured in 16 patients (4.5%). Measurements of SS can be used to identify patients with cirrhosis with EVs or high-risk EVs. A cutoff SS was identified that could rule out the presence of varices and could be used as an initial noninvasive screening test; UMIN Clinical Trials Registry number, UMIN000004363.

Prediction of Bleeding Etiology: The Clinician is Vindicated!

Prediction of Bleeding Etiology: The Clinician is Vindicated!

Transjugular intrahepatic portosystemic shunt with expanded-polytetrafuoroethylene-covered stents in non-cirrhotic patients with portal cavernoma

Aims To evaluate the feasibility and efficacy of Transjugular intrahepatic portosystemic shunt (TIPS) in non-cirrhotic patients with symptomatic portal hypertension secondary to portal cavernoma. Methods Our cohort includes 13 consecutive patients. Eleven were considered for Transjugular intrahepatic portosystemic shunt placement for complications not manageable by medical/endoscopic treatment and two because of the need of oral anticoagulation in presence of high-risk varices. Expanded-polytetrafluoroethylene-covered stents were used in all. Results One of the 13 patients was excluded because of a thrombosis of the superior cava and jugular veins. In 10 patients, Transjugular intrahepatic portosystemic shunt was successfully implanted [83.3%; 95% confidence interval: 52–98%]. One patient had an early shunt dysfunction with recurrence of variceal bleeding which required an emergency surgical shunt. Late shunt dysfunction occurred in two patients, successfully treated with angioplasty and re-stenting. Two patients experienced an episode of encephalopathy. Conclusions Transjugular intrahepatic portosystemic shunt is feasible in most of the patients with portal cavernoma and should be considered in those with severe complications uncontrolled by conventional therapy. The use of Transjugular intrahepatic portosystemic shunt to achieve a lifelong anticoagulation therapy in selected patients with high-risk varices may be another possible indication. These patients should be referred to selected Units with large experience in Transjugular intrahepatic portosystemic shunt placement.

Prophylactic sclerotherapy in high-risk cirrhotics selected by endoscopic criteria: A multicenter randomized controlled trial

Controlled trials of sclerotherapy for the prevention of the first variceal hemorrhage in cirrhotics have given conflicting results. In the present study, 106 cirrhotics were randomized to sclerotherapy (55 patients) or control group (51 patients). Admission criteria were no history of previous variceal bleeding and the presence of high-risk varices, i.e., a variceal score ≤ 0 according to Beppu et al. Sclerotherapy sessions were performed at time zero, 7 days, 30 days, and then monthly until eradication. Follow-up endoscopies were performed at 6-month intervals thereafter. Control patients underwent repeat endoscopy at 6-month intervals. Bleeding episodes were treated by sclerotherapy in both groups, whenever possible. Mean follow-up was 24 months. Analysis of the results was performed by the intention-to-treat method. Variceal bleeding occurred in 19 sclerotherapy patients (34.5%) and in 17 controls (35.4%, P = NS). Overall mortality was 34.5% in sclerotherapy patients and 50% in controls (P = NS). Seven of the 19 sclerotherapy patients (36.8%) and 11 of the 17 controls (64.7%) who bled died of hemorrhage (P < 0.05, log-linear model). It is concluded that prophylactic sclerotherapy does not reduce the incidence of first variceal bleeding in cirrhotics. However, there seems to be a trend toward a lower bleeding-related mortality in sclerotherapy patients than in controls.