|Year : 2022 | Volume
| Issue : 1 | Page : 26-32
Spleen stiffness measurement based on shear-wave elastography for noninvasive assessment of esophageal varices in liver cirrhosis cases
Walid K Soliman1, Khaled A Eid2, Ahmed Q Mohammad2
1 Department of Gastroenterology, Center of Cardiac and Digestive System, Sohag, Egypt
2 Department of Hepatology, Gastroenterology, and Infectious Disease, Faculty of Medicine, Al-Azhar University, Assiut, Egypt
|Date of Submission||01-Feb-2021|
|Date of Decision||15-Mar-2021|
|Date of Acceptance||07-Apr-2021|
|Date of Web Publication||4-Mar-2022|
BSc Walid K Soliman
Department of Gastroenterology, Center of Cardiac and Digestive System, Sohag 82524
Source of Support: None, Conflict of Interest: None
Background and aim Several laboratory tests and procedures have been considered as noninvasive prediction of esophageal varices (OV). This study assessed the usefulness of shear-wave elastography in splenic stiffness measurement (SSM) as a noninvasive assessment for OV prediction.
Patients and methods This study was performed on 100 cases in Sohag Cardiology and Gastroenterology 1Center who were categorized into three groups: group A: (n=40) included liver cirrhosis of any cause proved clinically, laboratory, and by ultrasound; group B: (n=30) included chronic hepatitis of any cause; and group C: (n=30) included nonhepatic cases attending the hospital with gastrointestinal tract complaints. All cases have been subjected to full history taking and clinical examination before classification, complete blood count, alanine aminotransferase, aspartate transaminase, serum albumin, coagulation profile and serum bilirubin, hepatitis C virus antibody (HCV Ab) and hepatitis B surface antigen (HB Ag), abdominal ultrasonography, SSM by shear-wave elastography, and upper endoscopy for diagnosing of OV.
Results As regards to abdominal ultrasound and upper endoscopy, significant differences were noted between three groups regarding spleen, spleen diameter, SSM, ascites, and OV (as 27.5 and 65% cases in group I had ascites and OV versus no cases in groups II and III as P<0.001). As regards to spleen diameter and SSM, significant increase was noted in group A than B and C, but insignificant differences were noted among groups B and C. As regards to OV grades in group A, there were five cases with grade I, nine cases with grade II, five cases with grade III, and seven cases with grade IV. Considerable positive correlations were noted among OV grades and acoustic radiation force impulse elastography (r=0.904, P <0.001).
Conclusion SSM by shear-wave elastography is a useful noninvasive parameter for detection of OV presence and grading in cases of liver cirrhosis.
Keywords: cirrhosis, noninvasive, esophageal varices, shear-wave elastography, spleen stiffness
|How to cite this article:|
Soliman WK, Eid KA, Mohammad AQ. Spleen stiffness measurement based on shear-wave elastography for noninvasive assessment of esophageal varices in liver cirrhosis cases. Al-Azhar Assiut Med J 2022;20:26-32
|How to cite this URL:|
Soliman WK, Eid KA, Mohammad AQ. Spleen stiffness measurement based on shear-wave elastography for noninvasive assessment of esophageal varices in liver cirrhosis cases. Al-Azhar Assiut Med J [serial online] 2022 [cited 2022 Jun 29];20:26-32. Available from: http://www.azmj.eg.net/text.asp?2022/20/1/26/339069
| Introduction|| |
The existence of esophageal varices (OV) is a significant side effect of portal hypertension that might develop in up to 90% of cirrhotic cases. Variceal bleeding is a life-threatening event. Accordingly, guidelines suggested that upper gastrointestinal tract (GIT) endoscopy should be repeated one to three years later based on the particular condition and the outcome of the first endoscopy for variceal identification in all cirrhotic patients .
Even so, as endoscopy is an uncomfortable, painful, invasive, and expensive procedure, a generalized screening program of periodic upper endoscopy in cases with cirrhosis can result in reduced implementation .
So many authors have therefore assembled predictor variables to differentiate patients with cirrhosis at a significant probability of varices from those at reduced probability, thereby preventing endoscopic examination in the latter group .
The following laboratory indices used to be determined as noninvasive measures to predict OV in hepatic cases: aspartate transaminase (AST)-to-alanine aminotransferase (ALT) ratio, platelet count/spleen diameter ratio [as the ratio of platelet count (/mm3) to bipolar splenic diameter in millimeters], and AST-to-platelet ratio index [(AST/ULN)×100]/platelet count (109/l) (ULN=standard upper limit and set to 40 IU/l)] .
Regarding scanning modalities, it has already been recommended that the necessity or prevalence of endoscopic scanning for patients with cirrhosis can be overlooked by MRI and CT scanning. In addition, SS estimation using shear-wave–virtual touch tissue quantification (VTTQ) was suggested to predict the existence of OV .
The spleen of cirrhotic cases was characterized by more fibrosis, angiogenesis, and hyperactivation of the lymphoid compartment of the spleen, not only by passive congestion related to PH. These splenomegaly-induced modifications could significantly raise SS and could be evaluated by transient elastography or VTTQ itself .
This trial assessed the usefulness of spleen stiffness (SS) measurement in prediction of OV.
| Patients and methods|| |
This trial was performed on 100 cases in Sohag Cardiology and Gastroenterology Center from May 2018 to July 2019 after approval from the Ethical Committee and obtaining of the patient’s informed consent.
Cases were classified into three groups:
- Group A: (n=40) liver cirrhosis of any cause proved clinically, laboratory, and by ultrasound.
- Group B: (n=30) chronic hepatitis of any cause.
- Group C: (n=30) nonhepatic cases coming to the hospital with GIT complaints.
- Acute hepatic failure.
- Variceal hemorrhage.
- Hepatic cancer.
- Thromboembolism of portal, splenic, or hepatic veins.
- Treatment with B-blockers.
- Transjugular intrahepatic portosystemic shunt or liver transplantation.
- Cases with blood malignancy, that is, leukemia and lymphomas.
- Bilharzial splenomegaly.
- Lack of informed consent.
All cases were evaluated for:
- Full history, complete general, and local examination before categorization.
- Complete blood count, ALT, AST, serum albumin, coagulation profile, and serum bilirubin.
- Hepatitis C virus antibody (HCV Ab) and hepatitis B surface antigen (HB AG).
- Abdominal ultrasonography.
- Assessment of splenic stiffness by shear-wave elastography (VTTQ; Siemens device, Siemens S200 Acuson, Mapmed Imaging India Private Limited, Kozhikode)
- Upper endoscope for detection of OVs.
Data were fed to the computer and analyzed using IBM SPSS software package version 20.0 (IBM Corp., Armonk, New York, USA). Qualitative data were described using number and percent. The Kolmogorov–Smirnov test was used to verify the normality of distribution. Quantitative data were described using range (minimum and maximum), mean, SD, median, and interquartile range. Pearson correlation was used between quantitative variables. Significance of the obtained results was judged at the 5% level.
| Results|| |
Insignificant differences were noted among three groups according to age and gender (P=0.137, 0.939) ([Table 1]).
According to laboratory investigations, insignificant differences were noted between the three groups regarding total leukocytic count and direct bilirubin (P=0.266, 0.137), but significant differences were noted among three groups regarding hemoglobin, platelets, international normalized ratio, prothrombin concentration (PC), ALT, AST, total bilirubin, and albumin (P<0.001) ([Table 2]).
As regards to hemoglobin, platelets, and albumin, a significant decrease was noted in group A than B and C and in group B than C (P1<0.001, <0.001, <0.001; P2<0.001, <0.001, <0.001; P3=0.027, <0.001, 0.003, respectively) ([Table 2]).
As regards to international normalized ratio and total bilirubin, a significant increase was noted in group A than B and C (P1<0.001, <0.001; P2<0.001, <0.001, respectively), but insignificant differences were detected between B and C groups (P3=0.661, 0.315, respectively) ([Table 2]).
As regards to PC, a significant decrease was noted in group A than B and C (P1<0.001; P2<0.001), but insignificant differences were detected between groups B and C (P3=0.394).
As regards to ALT and AST, a significant increase was observed in group A than B and C and in group B than C (P1<0.001, <0.001; P2<0.001, <0.001; P3=0.007, 0.009, respectively) ([Table 2]).
Significant differences were noted among three groups regarding HCV and HBV (P<0.001, 0.013) ([Table 3]).
According to abdominal ultrasound and upper endoscopy, significant differences were noted among three groups regarding spleen, spleen diameter, splenic stiffness, ascites, and OV (P<0.001). As regards to spleen diameter and splenic stiffness, a significant increase was observed in group A than B and C (P1<0.001, <0.001; P2<0.001, <0.001, respectively), but there were insignificant differences among groups B and C (P3=0.965, 0.390, respectively) ([Table 4]).
According to OV grades in group A, there were five cases with grade I, nine cases with grade II, five cases with grade III, and seven cases with grade IV.
Strong positive significant correlations were noted among OV grades and point shear-wave VTTQ (r=0.904, P<0.001).
At cutoff greater than 2.9 m/s of acoustic radiation force impulse (ARFI) to predict OV, sensitivity was 100, specificity was 93.24, positive predictive value (PPV) was 83.9, negative predictive value (NPV) was 100, area under then curve (AUC) was 0.972, and P value was less than 0.001 ([Figure 1]).
|Figure 1 Receiver operating characteristic curve of virtual touch tissue quantification to predict esophageal varices.|
Click here to view
| Discussion|| |
It is strongly advised that all cirrhotic patients perform esophagogastroduodenoscopy for OV identification. The high invasiveness of esophagogastroduodenoscopy, however, contributes to healthcare expense and patient anxiety .
In order to estimate the existence and size of OV, several noninvasive methods have evolved, like fibrosis serum marker, liver stiffness (LS), SS, and LS-spleen diameter to platelet ratio score .
The hepatic and SS assessment using elastography has been suggested as a promising tool for predicting EV .
In the current trial, significant differences were noted between three groups regarding spleen, spleen diameter, splenic stiffness, ascites, and OV by abdominal ultrasound and upper endoscopy (as 27.5% and 65% cases in group I had ascites and OV versus no cases in groups II and III as P <0.001). Also, significant increases were noted in groups A than B and C in splenic diameter and splenic stiffness (P1<0.001, <0.001; P2<0.001, <0.001, respectively), but insignificant differences have been observed between groups B and C (P3=0.965, 0.390, respectively).
In accordance with Bota et al. , they enrolled 82 participants (15 normal, 57 cirrhosis cases, and 10 with varying degrees of hepatic fibrosis) who reported considerable differences between SS and liver cirrhosis in nonhepatic cases (P<0.001)
Similar findings were reported by Kim et al. , as they found that the spleen diameter was also higher in cases with varices than in those without varices (P <0.001).
Also, in accordance with us, Mahmoud Hashim and colleagues found that there were significant differences among cases with and without OV as regards to splenic diameter and SS. The mean value of SS in cases without EV was 34.1±9.2 kPa (range: 24.7–45.1), whereas for cases with EV, it was 61.2±14.2 kPa (range: 34.2–94.1) .
In the study by Zaki and colleagues, by abdominal ultrasound, in more than 76% of cases, splenic enlargement was found, 80% moderate, and 10% mild without a case of enormous splenic enlargement. In 45 cases of cirrhotic disease, ascites were present. In 32 cirrhotic cases, upper GIT endoscopy revealed the presence of gastroesophageal varicose veins. OV was found in 26 cases, and gastric varices were present in six cases. In 28 cirrhotic cases, no EV could be identified 
The spleen size above 15 cm was found to be a complementary indicator of varices by Tag-Aden et al. .
In this study, according to OV grades in group A, there were five cases with grade I, nine cases with grade II, five cases with grade III, and seven cases with grade IV.
Also, in accordance with us, Mahmoud Hashim and colleagues found that among those with OV, 19 (20.7%) cases had grade 1, 17 (18.4%) cases had grade 2, and 23 (25%) cases had grade 3. Moreover, seven (7.6%) cases who had gastric varices also had OV .
Likewise, Colecchia and colleagues measured SS with hepatitis C virus-induced cirrhosis in 100 consecutive instances. Fifty-three (53%) of the 100 cases had varices. Of these, 27 cases (51%) had OV grade I, 20 (38%) had OV grade II, and six (11%) had OV grade III. .
In Kim and colleagues, a prospective retrospective study, endoscopic examination of OV was carried out for a total of 125 cirrhotic instances. Endoscopic analysis showed variceal existence in 77 (61.6%) cases, with varices F1, F2, and F3 in 25 (20.0%), 37 (29.6%), and 15 (12.0%) cases, respectively .
In this study, strong positive significant correlations were noted among OV grades and point shear-wave (VTTQ/ARFI) (r=0.904, P<0.001).
As demonstrated in the trial by Fierbinteanu-Braticevici et al. , significant correlations were noted among ARFI and the presence of OV in cirrhotic cases.
In harmony with this finding, Takuma et al.  found that SS assessed by shear-wave elastography reported a considerable correlation with the severity of OV.
In their subsequent study, Takuma et al.  found that both SS and hepatic stiffness assessed by the VTTQ scan were linearly correlated with varice grading, and the coefficients of correlations among SS and HVPG were considerably more than those among LS and HVPG.
Similarly, 145 newly diagnosed cirrhotic cases were included in the analysis by Bota et al. , and the LS and SS tested by VTTQ elastography were statistically significantly higher in cases with substantial OV relative to those without OV or grade 1 OV
Mahmoud Hashim et al.  also found a significant difference between cases with high-risk esophageal varices (HREV) and those without HREV according to LS and SS (P<0.001).
Bota and colleagues, on the other hand, do not find VTTQ to be a useful tool in the assessment of OV life and gravity. There were no major variations between the mean SS for cases with and without OV (P=0.16) and even for cases with miscellaneous OV grades (grade I vs. grade II, P=0.88; grade I vs. grade III, P=0.46; and grade II vs. grade III, P=0.37) .
There were no major variations in APRI in cases with varices relative to those without varices, according to Kim et al. .
Elkrief and colleagues conducted a study on 79 cases with cirrhosis, and 51 (65%) of them had HREV. According to LS and SS, no differences were observed between cases with and without HREV .
Additionally, VTTQ, a recent alternative research that tests tissue elasticity and its efficacy in obese or ascetic cases, is one of the most studied elastography methods ,. In this study, at cutoff greater than 2.9 of VTTQ to predict OV, sensitivity was 100, specificity was 93.24, PPV was 83.9, NPV was 100, AUC was 0.972, and P value was less than 0.001.
The PV of LS and SS evaluated by VTTQ for detection of substantial OV was evaluated by Vermehren et al. , and the area under the receiver operating characteristic (AUROC) curves were close to those observed in this study.
Also, the study of Fierbinteanu-Braticevici and colleagues showed no substantial variations among the optimum ARFI cutoff values in the prediction of varices, AUROC=0.972, in the identification of cases with varices requiring treatment. The VTTQ/ARFI cutoff values to exclude and include the variceal bleeding risk were less than 3.20 and less than 3.80 ms/s, respectively. The predictive negative value is notable for a cutoff value of 3.20 m/s (99%) to remove cases of varices requiring treatment .
Regarding VTTQ, it had 96.4% sensitivity, 92% specificity, 96.4% VPP, 92% VPN, and 95% precision for cirrhosis prediction for a cutoff value of 1.8 m/s .
Similarly, in the report by Takuma et al. , SS measurements using VTTQ elastography in HCV cases were successful in variceal detection (optimal SS cutoff of 3.18 m/s with 98.4% NPV, 98.5% sensitivity and 75% accuracy) and prediction of the high-risk variceal existence (optimal SS cutoff of 3.30 m/s with 99.4% NPV, 98.9% sensitivity, and 72.2% accuracy).
In the study by Bota and colleagues, the VTTQ technique had a good predictive value with 85.2% sensitivity, 91.7% specificity, and 87.1% accuracy (AUROC=0.91) for the diagnosis of cirrhosis. The accuracy improved when we combined SS with LS, but the frequency of EV or variceal bleeding could not be predicted .
A meta-analysis by Xiao et al.  reported that the mean AUCs for APRI and FIB-4 were 0.72 and 0.76, respectively, for substantial fibrotic detection.
The SS evaluated by means of ARFI was considered by Bota and colleagues. The best SS cutoff value was greater than 2.55 m/s (AUROC: 0.578, P=0.004, 96.7% sensitivity, 21% specificity, 47.6% PPV, 89.4% NPV, and 53.1% accuracy) for predicting substantial EV .
The study included 135 cirrhosis cases and SS estimated the existence of OV with 75.2 percent accuracy for a cutoff value greater than 52.5 kPa. According to Stefanescu et al. , the existence of OV was predicted at 72.2% precision for an LS value greater than 28 kPa.
Grgurevic and colleagues conducted a study on 87 cases with cirrhosis (mainly alcoholic and HCV), and 54 of them had OV. A cutoff value 30.3 kPa for SS had a sensitivity of 79.6% and specificity of 75.8% for the detection of OV existence .
Stefanescu and colleagues conducted a trial on 73 cirrhotic cases. A cutoff point for SS was 38 kPa, with AUROC of 0.747 .
Differences between the results can be explained by many factors. First, we used a different SWE system that had not been used before for EV prediction. According to the guidelines of the European Federation of Societies for Ultrasound in Medicine and Biology, devices using an identical technical approach but manufactured by various companies had various traits due to various processes for calculating the speed of the shear-wave. Second, our research included cases of compensated and decompensated cirrhosis, while other studies only included cases of compensated cirrhosis. Third, other research included only HCV-related cirrhosis, while we included various etiologies of cirrhosis.
| Conclusions|| |
Our research will help to identify splenic stiffness as a reliable tool and a limitless method for gastroenterologists to be utilized in cirrhotic population evaluation and to minimize the number of endoscopic tests. The measurement of SS by SWE is a valuable noninvasive parameter for prediction of EV presence and grading in cases with HCV-related cirrhosis. We assume, however, that ARFI measurement of SS is an ideal tool to be used in clinical practice for the screening of cirrhotic cases to detect the existence, seriousness, and bleeding risk of OV to alleviate variceal hemorrhage-related healthcare expenses.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Gao L, Meng F, Cheng J, Li H, Han J, Zhang W. Prediction of oesophageal varices in patients with primary biliary cirrhosis by non-invasive markers. Arch Med Sci 2017; 13:370.
Kovacs TO, Jensen DM. Varices: esophageal, gastric, and rectal. Clin Liver Dis 2019; 23:625–642.
Bell JA, Kaye TL, Guthrie JA. Imaging the liver and biliary tract. Medicine 2019; 39:511–517.
Adeyemi O, Burke K, Winston C, Markham S, Taussig D, Go B et al.
Fibrosis surveillance by transient elastography in patients with untreated hepatitis C infection. Open Forum Infect Dis 2018; 5:652.
Berzigotti A, Bosch J, Boyer TD. Use of noninvasive markers of portal hypertension and timing of screening endoscopy for gastroesophageal varices in patients with chronic liver disease. Hepatology 2014; 59:729–731.
Deng H, Qi X, Guo X. Diagnostic accuracy of APRI, AAR, FIB-4, FI, King, Lok, Forns, and FibroIndex scores in predicting the presence of esophageal varices in liver cirrhosis: a systematic review and meta-analysis. Medicine 2015; 94.
Colecchia A, Montrone L, Scaioli E, Bacchi–Reggiani ML, Colli A, Casazza G et al.
Measurement of spleen stiffness to evaluate portal hypertension and the presence of esophageal varices in patients with HCV-related cirrhosis. Gastroenterology 2012; 143:646–654.
Bota S, Sporea I, Şirli R, Popescu A, Dănilă M, Şendroiu M et al.
Spleen assessment by Acoustic Radiation Force Impulse Elastography (ARFI) for prediction of liver cirrhosis and portal hypertension. Med Ultrasond 2010; 12:213–217.
Kim HY, Jin EH, Kim W, Lee JY, Woo H, Oh S et al.
The role of spleen stiffness in determining the severity and bleeding risk of esophageal varices in cirrhotic patients. Medicine 2015; 94:94.
Mahmoud Hashim A, Shakweer M, Attia F, Awadallah H, Elraaey F, Ibrahem A. Measurement of liver and spleen stiffness by shear wave elastography as a noninvasive evaluation of esophageal varices in hepatitis C virus-related cirrhosis. Al-Azhar Assiut Med J 2017; 15:111–116. [Full text]
Zaki M, Hazem M, Elsamman M. Shear wave elastography in assessment of liver stiffness and prediction of gastro-esophageal varices in patients with liver cirrhosis. Egypt J Radiol Nucl 2019; 50:16.
Tag-Adeen M, Alsenbesy M, Ghweil AA, Elrazek MAHA, Elgohary EA, Sallam MM et al.
Liver stiffness measurement and spleen diameter as predictors for the presence of esophageal varices in chronic hepatitis C patients. Medicine 2017; 96:e8621.
Fierbinteanu-Braticevici C, Tribus L, Peagu R, Petrisor A, Baicus C, Cretoiu D et al.
Spleen stiffness as predictor of esophageal varices in cirrhosis of different etiologies. Sci Rep 2019; 9:1–7.
Takuma Y, Nouso K, Morimoto Y, Tomokuni J, Sahara A, Toshikuni N et al.
Measurement of spleen stiffness by acoustic radiation force impulse imaging identifies cirrhotic patients with esophageal varices. Gastroenterology 2013; 144:92–101.
Takuma Y, Nouso K, Morimoto Y, Tomokuni J, Sahara A, Takabatake H et al.
Portal hypertension in patients with liver cirrhosis: diagnostic accuracy of spleen stiffness. Radiology 2016; 279:609–619.
Bota S, Sporea I, Sirli R, Focsa M, Popescu A, Danila M et al.
Can ARFI elastography predict the presence of significant esophageal varices in newly diagnosed cirrhotic patients? Ann Hepatol 2012; 11:519–525.
Elkrief L, Rautou PE, Ronot M, Lambert S, Dioguardi Burgio M, Francoz C et al.
Prospective comparison of spleen and liver stiffness by using shear-wave and transient elastography for detection of portal hypertension in cirrhosis. Radiology 2015;275:589-598.
Takuma Y, Morimoto Y, Takabatake H, Toshikuni N, Tomokuni J, Sahara A et al.
Measurement of spleen stiffness with acoustic radiation force impulse imaging predicts mortality and hepatic decompensation in patients with liver cirrhosis. Clin Gastroenterol Hepatol 2017; 15:1782–1790.
Vermehren J, Polta A, Zimmermann O, Herrmann E, Poynard T, Hofmann WP et al.
Comparison of acoustic radiation force impulse imaging with transient elastography for the detection of complications in patients with cirrhosis. Liver Int. 2012; 32:852–858.
Sporea I, Şirli R, Popescu A, Danilă M. Acoustic Radiation Force Impulse (ARFI)-a new modality for the evaluation of liver fibrosis. Med Ultrasond 2010; 12: 26–31.
Xiao G, Yang J, Yan L. Comparison of diagnostic accuracy of aspartate aminotransferase to platelet ratio index and fibrosis-4 index for detecting liver fibrosis in adult patients with chronic hepatitis B virus infection: a systemic review and meta-analysis. Hepatology 2015; 61:292–302.
Stefanescu H, Grigorescu M, Lupsor M, Procopet B, Maniu A, Badea R. Spleen stiffness measurement using Fibroscan for the noninvasive assessment of esophageal varices in liver cirrhosis patients. J Gastroenterol Hepatol 2011; 26:164–170.
Grgurević I, Bokun T, Mustapić S, Trkulja V, Heinzl R, Banić M et al.
Real-time two-dimensional shear wave ultrasound elastography of the liver is a reliable predictor of clinical outcomes and the presence of esophageal varices in patients with compensated liver cirrhosis. Croat Med J 2015; 56:470–481.
Stefanescu H, Allegretti G, Salvatore V, Piscaglia F. Bidimensional shear wave ultrasound elastography with supersonic imaging to predict presence of oesophageal varices in cirrhosis. Liver Int 2017; 37:1405-.
[Table 1], [Table 2], [Table 3], [Table 4]