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.

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.

Role of spleen elastography in patients with chronic liver diseases

The development of liver cirrhosis and portal hypertension(PH), one of its major complications, are structural and functional alterations of the liver, occurring in many patients with chronic liver diseases(CLD). Actually the progressive deposition of hepatic fibrosis has a key role in the prognosis of CLD patients. The subsequent development of PH leads to its major complications, such as ascites, hepatic encephalopathy, variceal bleeding and decompensation. Liver biopsy is still considered the reference standard for the assessment of hepatic fibrosis, whereas the measurement of hepatic vein pressure gradient is the standard to ascertain the presence of PH and upper endoscopy is the method of choice to detect the presence of oesophageal varices. However, several non-invasive tests, including elastographic techniques, are currently used to evaluate the severity of liver disease and predict its prognosis. More recently, the measurement of the spleen stiffness has become particularly attractive to assess, considering the relevant role accomplished by the spleen in splanchnic circulation in the course of liver cirrhosis and in the PH. Moreover, spleen stiffness as compared with liver stiffness better represents the dynamic changes occurring in the advanced stages of cirrhosis and shows higher diagnostic performance in detecting esophageal varices. The aim of this review is to provide an exhaustive overview of the actual role of spleen stiffness measurement as assessed by several elastographic techniques in evaluating both liver disease severity and the development of cirrhosis complications, such as PH and to highlight its potential and possible limitations.

Noninvasive assessment of portal hypertension in cirrhosis:Liver stiffness and beyond

Liver stiffness measurement(LSM)is a good,but still limited tool to noninvasively assess complications and prognosis in patients with advanced liver disease.This review aims to consider the role of LSM for the diagnosis of portal hypertension-related complications and for assessment of prognosis in cirrhotic patients,and to highlight the drawbacks as well as some alternatives for improving the performance.Hence,this field is far from being closed,and deserves more attention.There is still a place for more carefully designed studies to find new,innovative and reliable approaches.

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 tests for the prediction of primary hepatocellular carcinoma

Hepatocellular carcinoma(HCC)is one of the most common malignancies in the world and it is one of the main complications of cirrhosis and portal hypertension.Even in the presence of a well-established follow-up protocol for cirrhotic patients,to date poor data are available on predictive markers for primary HCC occurrence in the setting of compensated advanced chronic liver disease patients(cACLD).The gold standard method to evaluate the prognosis of patients with cACLD,beyond liver fibrosis assessed with histology,is the measurement of the hepatic venous pressure gradient(HVPG).An HVPG≥10 mmHg has been related to an increased risk of HCC in cACLD patients.However,these methods are burdened by additional costs and risks for patients and are mostly available only in referral centers.In the last decade increasing research has focused on the evaluation of several,simple,non-invasive tests(NITs)as predictors of HCC development.We reviewed the currently available literature on biochemical and ultrasound-based scores developed for the noninvasive evaluation of liver fibrosis and portal hypertension in predicting primary HCC.We found that the most reliable methods to assess HCC risk were the liver stiffness measurement,the aspartate aminotransferase to platelet ratio index score and the fibrosis-4 index.Other promising NITs need further investigations and validation for different liver disease aetiologies.

Non-invasive splenic parameters of portal hypertension:Assessment and utility

BACKGROUND Portal hypertension is a major complication of cirrhosis that is associated with significant morbidity and mortality.The present gold-standard method to risk stratify and observe cirrhosis patients with portal hypertension is hepatic venous pressure gradient measurement or esophagogastroduodenoscopy.However,these methods are invasive,carry a risk of complications and are associated with significant patient discomfort.Therefore,non-invasive splenic parameters are of clinical interest as potential useful markers in determining the presence of portal hypertension.However,diagnostic accuracy and reproducibility remains unvalidated.AIM To assess the diagnostic accuracy of spleen stiffness,area and diameter in predicting the presence of portal hypertension.METHODS Of 50 patients with varying liver disease pathologies were prospectively recruited from the St.Mary’s Hospital Liver Unit in London;25 with evidence of portal hypertension and 25 with no evidence of portal hypertension.Liver stiffness,spleen stiffness,spleen diameter and spleen area were measured using the Philips Affiniti 70 elastography point quantification point shear wave elastography system.The aspartate aminotransferase-to-platelet-ratio-index(APRI)score was also calculated.Performance measures,univariate and multivariate logistic regression were used to evaluate demographic,clinical and elastography variables.Interclass correlation coefficient was used to determine the reproducibility of splenic area and diameter.RESULTS On univariate and individual performance,platelet count[area under the receiver operating characteristic(AUROC)0.846,P value<0.001],spleen area(AUROC 0.828,P value=0.002)and APRI score(AUROC 0.827,P value<0.001)were the most accurate variables in identifying the presence of portal hypertension.On multivariate logistic regression models constructed,the combination of spleen area greater than 57.90 cm2 and platelet count less than 126×10^9 had 63.2%sensitivity and 100%specificity,100%positive predictive value and 100%negative predictive value.An alternative combination of spleen stiffness greater than 29.99 kPa and platelet count less than 126×10^9 had 88%sensitivity,75%specificity,78.6%positive predictive value and 85.7%negative predictive value.An interclass correlation coefficient value of 0.98(95%CI:0.94-0.99,P value<0.001)and 0.96(95%CI:0.91-0.99,P value<0.001)were determined for inter-operator variability for spleen area and diameter respectively.CONCLUSION Spleen area,spleen stiffness and platelet count may be useful markers to assess the presence of portal hypertension in patients of various etiologies.

New insights on portal hypertension’s screening in people with cystic fibrosis

Cystic fibrosis-associated liver disease(CFLD)is a significant cause of morbidity and mortality affecting people with cystic fibrosis(PwCF)(1).Approximately 40%of PwCF have liver involvement,defined as the existence of any hepatic manifestation,including biochemical liver abnormalities(2).In a small percentage of these patients,liver involvement may ultimately result in the development of portal hypertension(PH)and its complications.The presence of at least two of the following variables-abnormal liver tests,abnormal liver ultrasound(US),abnormal physical examination with hepatosplenomegaly or histologic evidence of liver disease-were historically the basis for the European criteria to define CFLD(3).Nevertheless,the emergence of a new approach for liver assessment as liver elastography has led to the proposal of its inclusion in new diagnostic criteria(4).