|Year : 2017 | Volume
| Issue : 2 | Page : 111-116
Measurement of liver and spleen stiffness by shear wave elastography as a noninvasive evaluation of esophageal varices in hepatitis C virus-related cirrhosis
Alaa E Mahmoud Hashim1, Mustafa M Shakweer2, Farid F Attia1, Hany M Awadallah1, Fathya M Elraaey1, Abdelhakam M Ibrahem1
1 Department of Tropical Medicine, Al-Azhar University, New Damietta, Egypt
2 Department of Radiodiagnosis, Al-Azhar University, New Damietta, Egypt
|Date of Submission||11-Aug-2017|
|Date of Acceptance||12-Sep-2017|
|Date of Web Publication||21-Nov-2017|
Abdelhakam M Ibrahem
Department of Tropical Medicine, Al-Azhar University, New Damietta
Source of Support: None, Conflict of Interest: None
Background Several noninvasive methods have been developed to predict esophageal varices (EVs) in patients with cirrhosis aiming to restrict endoscopic screening. Recently, two-dimensional shear wave elastography (2D-SWE) was evaluated for this purpose. The aim of this study was to evaluate the use of 2D-SWE for liver stiffness measurement (LSM) and spleen stiffness measurement (SSM) for prediction of EV presence and grading.
Patients and methods This study included 100 patients with hepatitis C virus cirrhosis who were subjected to upper endoscopy for detection and grading of EV as well as LS and SS measurements using 2D-SWE.
Results There was a significant difference between patients with and without EV regarding LS and SS (P<0.001). The measurement LS at cutoff of 16.2 kPa and SS at cutoff of 42.7 kPa by 2D-SWE predicted the presence of EV with sensitivity of 89.8 and 94.9%, respectively, and specificity of 57.6 and 87.9%, respectively. Moreover, at cutoffs of 19.6 and 51.5 kPa for LS and SS, respectively, the presence of high-risk EV was predicted with sensitivity of 77.5 and 85%, respectively, and specificity of 63.4 and 84.6%, respectively.
Conclusion The measurement of LS and SS by 2D-SWE predicted the presence of EV and high-risk EV in patients with cirrhosis, with more sensitivity and specificity for SS than LS.
Keywords: elastography, esophageal varices, liver stiffness, spleen stiffness
|How to cite this article:|
Mahmoud Hashim AE, Shakweer MM, Attia FF, Awadallah HM, Elraaey FM, Ibrahem AM. 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;15:111-6
|How to cite this URL:|
Mahmoud Hashim AE, Shakweer MM, Attia FF, Awadallah HM, Elraaey FM, Ibrahem AM. 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 [serial online] 2017 [cited 2020 Feb 26];15:111-6. Available from: http://www.azmj.eg.net/text.asp?2017/15/2/111/218855
| Introduction and aim|| |
Esophageal varices (EVs) are mainly induced by portal hypertension , which is one of the most common consequences of chronic liver disease . All patients with cirrhosis are recommended to undergo esophagogastroduodenoscopy (EGD) for identifying EVs. However, the invasive nature of EGD leads to health care costs and patient discomfort .
Several noninvasive methods have emerged to predict the presence and size of EVs, such as serum fibrosis markers, liver stiffness (LS), spleen stiffness (SS), LS-spleen diameter to platelet ratio score ,. The measurement of liver and SS by elastography has been suggested as a promising tool for predicting EV . Among elastographic methods, transient elastography has been studied the most . However, transient elastography has limited effectiveness, especially in patients with ascites and obesity .
Real-time SWE is a promising new type of shear wave-based ultrasound technique for measuring LS and SS with high reliability and reproducibility .
The aim of this study was to evaluate the use of two-dimensional shear wave elastography (2D-SWE) for LS and SS measurements in patients with posthepatitis C virus (HCV) liver cirrhosis; as a noninvasive procedure, the hepatosplenic SWE outcomes will be correlated with EV grading by EGD in the studied patients with cirrhosis.
| Patients and methods|| |
This is a descriptive, analytical, and controlled study that was carried out at the Inpatient Unit of Tropical Medicine Department of Al-Azhar University (New Damietta) during the period from December 2016 to July 2017. All the patients were subjected to the following after obtaining an informed written consent.
- Cases group: it included 100 patients with HCV cirrhosis at any stage. Patients with hepatocellular carcinoma, portal vein thrombosis, hematological diseases, previous endoscopic sclerotherapy or band ligation, or previous β-blockers intake were excluded. We had eight patients with unsuccessful measurements of LS and SS by 2D-SWE. Thus, data from 92 patients were analyzed.
- Control group: it included 25 controls with no history of liver disease, normal laboratory investigations, and normal abdominal ultrasound, submitted to a justified diagnostic EGD because of indications other than liver cirrhosis (e.g. dyspepsia that is not responding to medical treatment). All of them had successful stiffness measurements.
All patients were subjected to the following:
- Detailed history taking, full clinical examination with BMI calculation, and laboratory investigations [complete blood picture, serum albumin, serum bilirubin, serum alanine aminotransferase (ALT) and aspartate aminotransferase, international normalized ratio, viral markers, HCV RNA, and serum α-fetoprotein].
- Upper gastrointestinal endoscopy for detection and grading of EV for study cases.
- EV were classified as follow : grade 1: small straight varices; grade 2: enlarged tortuous varices, occupying less than one-third of the lumen; grade 3: large, coil-shaped varices, occupying more than one-third of the lumen; then we classified patients into patients with no EV, grade 1 EV and patients with grade 2 and grade 3 [defined as high-risk esophageal varice (HREV)] ,.
- Abdominal ultrasound and SWE measurements: using ultrasound device Aplio 500 system (Toshiba, Tokyo, Japan), the following techniques are used:
- Routine abdominal ultrasound with assessment of the size, border, echogenicity, and the presence of any focal lesion for liver and spleen.
- Liver stiffness measurement (LSM):
- The examination was performed in the right lobe of the liver through intercostal spaces, after at least 6 h of fasting while the patient lying supine with the right arm in maximal abduction and breathing normally, with holding the breath for few seconds during the acquisition.
- Special attention to avoid any focal lesion, cardiac movement, vessels, biliary tracts, or artifacts.
- Size of the 2D-SWE sample box was about 3×3 cm, with circular region of interest (ROI) inside it.
- The stiffness measurement was obtained by placing the ROI in the area where the shear waves propagated uniformly assessed by looking at propagation map ([Figure 1]).
|Figure 1 Liver stiffness in a controls. This figure shows the color map (left) and the propagation map (right) of the shear waves displayed together. The reliability of measurement was tested by the propagation map as the lines are parallel to each other and the intervals between them are constant; thus, the measurement is considered reliable. Using the region of interest, the stiffness was 5.8 kPa.|
Click here to view
- When no reliable propagation map could be obtained in consecutive acquisitions in a period of 10 min, LSMs were considered failures.
- The median value of 10 consecutive measurements was used for statistical analysis.
- Spleen stiffness measurement (SSM): measurements were performed through the left intercostal spaces with left arm maximally extended and applying the same quality criteria as stated for LSMs ([Figure 2]).
|Figure 2 Spleen stiffness in a patient with cirrhosis. This figure shows measurement of spleen stiffness in patients with cirrhosis using two-dimensional shear wave elastography showing yellow-red color map with wide parallel lines in propagation map; meaning that higher stiffness with reliable measurement. spleen stiffness here was 51.8 kP.|
Click here to view
The collected data were recognized, tabulated, and analyzed using appropriate tests. Continuous variables were expressed in term of mean and SD and ordinal and nominal categorical data were described as number and percentage. The receiver operating characteristic (ROC) curve was performed to determine cutoff values for the studied technique. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were determined. A P value less than 0.05 was considered statistically significant.
| Results|| |
In the present work, there was no significant difference between cases and controls regarding sex, age, and BMI, whereas we found significant difference in all ultrasound and laboratory parameters except ALT between the two groups ([Table 1]). The mean value of LS and SS in controls was 5.8±1.3 and 16.3±1.5 kPa, respectively, whereas the mean value of LS and SS in cases group was 23.8±10.1 and 51±18.1 kPa, respectively.
Among patients with cirrhosis, 33 (35.9%) of them had no varices and 59 (64.1%) had EVs. Among those with EVs, 19 (20.7%) patients had grade 1, 17 (18.4%) patients had grade 2, and 23 (25%) patients had grade 3. Moreover, seven (7.6%) patients who had gastric varices also had EVs.
There was no significant difference between patients with and without EVs regarding age, sex, BMI, portal vein diameter, platelets count, ALT, aspartate aminotransferase, and international normalized ratio. There was significant difference between patient with and without EVs regarding LS, SS, Child’s grade, spleen diameter, and serum albumin and bilirubin levels ([Table 2]).
|Table 2 Mean±SD in patients with esophageal varice and those without esophageal varice|
Click here to view
The mean value of LS in patients without EV was 18.6±5.4 kPa (range: 14–36.1), whereas for patients with EV, it was 28.1±10.4 kPa (range: 14.3–56). The mean value of SS in patients without EV was 34.1±9.2 kPa (range: 24.7–45.1), whereas for patients with EV, it was 61.2±14.2 kPa (range: 34.2–94.1).
Using a cutoff value of 16.2 kPa for SWE of liver, LS had sensitivity of 89.8%, specificity of 57.6%, PPV of 79.1%, and NPV of 76% for differentiating those with EV from those without EV ([Table 3]). The area under the receiver operating characteristic (AUROC) curve for LS was 0.775 ([Figure 3]). A cutoff value of 42.7 kPa for SWE of spleen showed sensitivity of 94.9%, specificity of 87.9%, PPV of 93.3%, and NPV of 90.6% for differentiating those with EV from those without EV ([Table 3]). The AUROC curve for SS was 0.946 ([Figure 4]).
|Table 3 Cutoff values for liver stiffness and spleen stiffness for prediction of esophageal varice and prediction of high-risk esophageal varice|
Click here to view
|Figure 3 Receiver operating characteristic curve for liver stiffness (AUROC=0.775). AUROC, area under the receiver operating characteristic.|
Click here to view
|Figure 4 Receiver operating characteristic curve for spleen stiffness (AUROC=0.946). AUROC, area under the receiver operating characteristic.|
Click here to view
We also found significant difference between patients with HREV and those without HREV regarding LS and SS (P<0.001). The mean values of LS and SS in patients without HREV were 19.6±5.6 and 40.4±12.1 kPa, respectively, whereas the mean values of LS and SS in patient with HREV were 29.3±12.1 and 65±15 kPa, respectively. Using a cutoff value of 19.6 kPa for SWE of liver, LS had sensitivity of 77.5%, specificity of 63.4%, PPV of 62%, and NPV of 78.6% to differentiate those with HREV from those without. A cutoff value of 51.5 kPa for SWE of spleen showed sensitivity of 85%, specificity of 84.6%, PPV of 81%, and NPV of 88% to differentiate those with HREV from those without HREV ([Table 3]).
SS is more sensitive and specific than LS in predicting the presence of EV and identifying those with HREV.
| Discussion|| |
The present study was performed to evaluate the performance of LS and SS measured by 2D-SWE for noninvasive assessment of EV in patients with HCV-related cirrhosis.
The reported measurements values for LS and SS using the 2D-SWE yielded variable results with the use of different ultrasound systems. Up to our knowledge, there are no previous studies that measured LS or SS using 2D-SWE of Toshiba (Aplio 500) ultrasound system for prediction of EV. So, we are going to compare our results with another ultrasound systems using 2D-SWE.
The mean value of LS among our control group was 5.8±1.3 kPa, which was similar to the results of Yoon et al.  (4.56±1.44 kPa) and Franchi-Abella et al.  (6.53±1.38 kPa). The mean value of SS among controls was 16.3±1.5 kPa, which was similar to the results of Pawlus et al.  (16.6±2.5 kPa) and Leung et al.  (17.3±2.6 kPa).
In our patients with cirrhosis, failure rate of LSM and SSM was 8% owing to inability of the patients to hold the breath (5%) and high BMI of more than 36 (3%). According to European Federation of Societies for Ultrasound in Medicine and Biology guidelines, failure occurs up to 10% of cases reported in the published series . Elkrief et al.  reported success rate of 97 and 97% for LSM and SSM, respectively, whereas Procopet et al.  reported success rates for LSM and SSM of 99 and 66%, respectively. Obesity and poor breath hold are well known causes for elastographic measurements failure ,.
The mean value of LS in our patients with cirrhosis was 23.8±10.1 kPa, whereas for SS, it was 51±18.1 kPa. Other studies have reported variable results. Procopet et al.  had median value of LS 22.7±13.4 kPa and for SS 33.7±11.6 kPa. Jansen et al.  found median value of LS 28.7±20.1 kPa and for SS 35.5±22.9 kPa. Higher mean value of SS in our study can be explained by more decompensated patients, in addition to the wide range of SS in our study (24.7–94.1 kPa).
In our study, 59 (64.1%) patients had EV. We found significant difference in LS and SS between patients with and without EV. A cutoff value of 16.2 kPa for LS showed 89.8% sensitivity, 57.6% specificity, 79.1% PPV, and 76% NPV for prediction of the presence of EV (AUROC: 0.775). A cutoff value 42.7 kPa for SS showed 94.9% sensitivity, 87.9% specificity, 93.3% PPV, and 90.6% NPV for prediction of the presence of EV, with AUROC of 0.946.
Regarding the role of 2D-SWE in prediction of the presence of EV, we found only three studies ,,.
Grgurevic et al.  conducted a study on 87 patients with cirrhosis (mainly alcoholic and HCV), and 54 of them had EV. A cutoff value of 19.7 kPa for LS had a sensitivity of 83.3% and specificity of 66.6% for prediction of the presence of EV. A cutoff value 30.3 kPa for SS had a sensitivity of 79.6% and specificity of 75.8% for the prediction of presence of EV.
Kim et al.  conducted a study on 103 patients with compensated cirrhosis (mainly hepatitis B virus and alcoholic), and 40 of them had EV. A cutoff point of 13.9 kPa had a sensitivity of 75% and specificity of 88% for prediction of EV (AUROC: 0.887).
Stefanescu et al.  conducted a study on 73 patients with cirrhosis. A cutoff point of LS for prediction of EV was 19 kPa, with AUROC of 0.753, whereas 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 European Federation of Societies for Ultrasound in Medicine and Biology guidelines, systems that use the same technique but were developed by different manufacturers had different values owing to different methods to measure the shear wave’s speed . Second, our study included patients with compensated and decompensated cirrhosis whereas other studies had patients with compensated cirrhosis only. Third, other studies included different etiologies of cirrhosis, whereas we included HCV-related cirrhosis only.
To identify patients with HREV, we had 40 (43.4%) patients with HREV (grades 2 and 3 EV), with significant difference in LS and SS between patients with and without HREV.
A cutoff value of 19.6 kPa for LS showed 77.5% sensitivity, 63.4% specificity, 62% PPV, and 78.6% NPV for prediction of HREV. A cutoff value of 51.5 kPa for SS showed 85% sensitivity, 84.6% specificity, 81% PPV, and 88% NPV for prediction of HREV.
Regarding the role of 2D-SWE in prediction of HREV, we found only two studies ,.
Elkrief et al.  conducted a study on 79 patients with cirrhosis, and 51 (65%) of them had HREV. Neither LS nor SS differed between patients without and those with HREV. A cutoff value of 24.7 kPa for LS showed a sensitivity of 82% and specificity of 44% for prediction of HREV. For SS, a cutoff value of 32.3 had a sensitivity of 48% and specificity of 71% for prediction of HREV.
Kim et al.  did a study on 103 patients with compensated cirrhosis, and 13 (12.6%) of them had HREV. LS significantly differed between patients without and those with HREV. A cutoff point of 16.1 kPa for LS had a sensitivity of 84.6% and specificity of 85.6% for prediction of HREV.
The present study concluded that SS is more sensitive and specific than LS in prediction of the presence of EV as well as HREV.
These results agreed with a recent meta-analysis that evaluated the diagnostic performance of LSM and SSM for detecting EV using different elastographic techniques including 1892 patients. The summary sensitivity of SS and LS was 88 and 83%, respectively, while the specificity of SS and LS was 78 and 66%, respectively. For detecting HREV, the summary sensitivity of SS and LS was 83 and 82%, respectively, whereas the specificity of SS and LS was 57 and 52%, respectively .
Our study agreed with the previous meta-analysis that SS is superior for EV prediction than LS. In addition, the present study had reported better sensitivity and specificity of SS than the pooled sensitivity and specificity for the meta-analysis (including different elastographic techniques).
We should take into consideration that comparing results obtained by the different elastography techniques is challenging because terminology, reported parameters, shear wave frequency, and other technical factors are not standardized .
| Conclusion|| |
The measurement of LS and SS by 2D-SWE is a valuable noninvasive parameter for prediction of EV presence and grading in patients with HCV-related cirrhosis. SS has more sensitivity and specificity than LS in prediction of EV and identifying HREV. Furthermore, longitudinal studies are needed to confirm our data to reduce the endoscopic burden in the patients with cirrhosis.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Rosoøowski M, Hartleb M, Marek T, Milewski J, Linke K, Wallner G et al.
Therapeutic and prophylactic management of bleeding from esophageal and gastric varices: recommendations of the Working Group of the National Consultant for Gastroenterology. Prz Gastroenterol 2014; 9:63–68.
Garcia-Tsao G, Sanyal AJ, Grace ND. Prevention and management of gastroesophageal varices and variceal hemorrhage in cirrhosis. Hepatology 2007; 46:922–938.
Berzigotti A, Bosch J, Boyer TD. Use of noninvasive markers of portal hypertension and timing of screening endoscopy for gastro-esophageal varices in patients with chronic liver disease. Hepatology 2014; 59:729–731.
De Franchis R, Dell’Era A. Invasive and noninvasive methods to diagnose portal hypertension and esophageal varices. Clin Liver Dis 2014; 18:293–302.
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 (Baltimore) 2015; 94:e179.
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.
De Franchis R, Baveno VIF. Expanding consensus in portal hypertension: report of the Baveno VI Consensus Workshop: stratifying risk and individualizing care for portal hypertension. J Hepatol 2015; 63:743–752.
Castéra L, Foucher J, Bernard PH, Carvalho F, Allaix D, Merrouche W et al.
Pitfalls of liver stiffness measurement: a 5-year prospective study of 13,369 examinations. Hepatology 2010; 51:828–835.
Ferraioli G, Tinelli C, Zicchetti M, Above E, Poma G, Di Gregorio M, Filice C. Reproducibility of real-time shear wave elastography in the evaluation of liver elasticity. Eur J Radiol 2012; 81:3102–3106.
De Franchis R. Revising consensus in portal hypertension: report of the Baveno V consensus workshop on methodology of diagnosis and therapy in portal hypertension. J Hepatol 2010; 53:762–768.
Bota S, Sporea I, Sirli R, Focsa M, Popescu A, Danila M, Strain M. Can ARFI elastography predict the presence of significant esophageal varices in newly diagnosed cirrhotic patients? Ann Hepatol 2012; 11:519–525.
Calvaruso V, Di Marco V, Bronte F, Conte E, Bastard C, Simone F, Craxi A. High spleen stiffness is related to presence of esophageal varices in patients with HCV cirrhosis. J Hepatol 2012; 56:S409.
Yoon JH, Lee JM, Han JK, Cho BI. Shear wave elastography for liver stiffness measurement in clinical sonographic examinations: evaluation of intraobserver reproducibility, technical failure, and unreliable stiffness measurements. J Ultrasound Med 2014; 33:437–447.
Franchi-Abella S, Corno L, Gonzales E, Antoni G, Fabre M, Ducot B et al.
Feasibility and diagnostic accuracy of supersonic shear-wave elastography for the assessment of liver stiffness and liver fibrosis in children: a pilot study of 96 patients. Radiology 2016; 278:554–562.
Pawluś A, Inglot MS, Szymańska K, Kaczorowski K, Markiewicz BD, Kaczorowska A et al.
Shear wave elastography of the spleen: evaluation of spleen stiffness in healthy volunteers. Abdom Radiol 2016; 41:2169–2174.
Leung VYF, Shen J, Wong VWS, Abrigo J, Wong GLH, Chim AML. Quantitative elastography of liver fibrosis and spleen stiffness in chronic hepatitis B carriers: comparison of shear-wave elastography and transient elastography with liver biopsy correlation. Radiology 2013; 269:910–918.
Dietrich CF, Bamber J, Berzigotti A, Bota S, Cantisani V, Castera L et al.
EFSUMB guidelines and recommendations on the clinical use of liver ultrasound elastography, Update 2017 (Long Version). Ultraschall Med 2017; 38:e16–e47.
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.
Procopet B, Berzigotti A, Abraldes JG, Turon F, Hernandez-Gea V, García-Pagán JC, Bosch J. Real-time shear-wave elastography: applicability, reliability and accuracy for clinically significant portal hypertension. J Hepatol 2015; 62:1068–1075.
Cassinotto C, Boursier J, De Lédinghen V, Lebigot J, Lapuyade B, Cales P et al.
Liver stiffness in nonalcoholic fatty liver disease: a comparison of Supersonic Shear Imaging, FibroScan and ARFI with liver biopsy. Hepatology 2016; 63:1817–1827
Jansen C, Bogs C, Verlinden W, Thiele M, Möller P, Görtzen J et al.
Algorithm to rule out clinically significant portal hypertension combining Shear-wave elastography of liver and spleen: a prospective multicentre study. Gut 2016; 65:1057–1058.
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.
Kim TY, Kim TY, Kim Y, Lim S, Jeong WK, Sohn JH. Diagnostic performance of shear wave elastography for predicting esophageal varices in patients with compensated liver cirrhosis. J Ultrasound Med 2016; 35:1373–1381.
Stefanescu H, Allegretti G, Salvatore V, Piscaglia F. Bidimensional shear wave ultrasound elastography with supersonic imaging to predict presence of esophageal varices in cirrhosis. Liver Int 2017; 37:1405.
Ma X, Wang L, Wu H, Feng Y, Han X, Bu H, Zhu Q. Spleen stiffness is superior to liver stiffness for predicting esophageal varices in chronic liver disease: a meta-analysis. PLoS One 2016; 11:e0165786.
Barr RG, Ferraioli G, Palmeri ML, Goodman ZD, Garcia-Tsao G, Rubin J et al.
Elastography assessment of liver fibrosis: society of radiologists in ultrasound consensus conference statement. Radiology 2015; 276:845–861.
[Figure 1], [Figure 2], [Figure 3], [Figure 4]
[Table 1], [Table 2], [Table 3]
|This article has been cited by|
||Shear wave elastography in assessment of liver stiffness and prediction of gastro-esophageal varices in patients with liver cirrhosis
| ||Mohammed Zaki,Mohammed Hazem,Mahmoud Elsamman |
| ||Egyptian Journal of Radiology and Nuclear Medicine. 2019; 50(1) |
|[Pubmed] | [DOI]|
||Usefulness of noninvasive methods including assessment of liver stiffness by 2-dimensional shear wave elastography for predicting esophageal varices
| ||Hae Won Yoo,Young Seok Kim,Sang Gyune Kim,Jeong-Ju Yoo,Soung Won Jeong,Jae Young Jang,Sae Hwan Lee,Hong Soo Kim,Young Don Kim,Gab Jin Cheon,Baekgyu Jun,Boo Sung Kim |
| ||Digestive and Liver Disease. 2019; |
|[Pubmed] | [DOI]|