Dual Energy CT as a Noninvasive Method to Screen for Gastroesophageal Varices
Phase: NA
Conditions: Gastroesophageal Varices
Sponsor: University of Alabama at Birmingham

 
 
Dual Energy CT as a Noninvasive Method to Screen for 
Gastroesophageal Varices 
 
Study Protocol & Statistical Analysis Plan 
 
NCT03910413    
 
 
Date of Last Protocol Approval 
02/22/2023 
 
 
Andrew Smith MD PhD 
Vice Chair of Clinical Research and Associate Professor 
Director of Human Imaging Shared Facility (HISF) 
Chief of Body CT 
Oncologic and Abdominal Radiologist 
University of Alabama at Birmingham 
Birmingham, AL 35294 
 
 
 
 
 
 
 
 
 
 
 
 

Dual Energy CT as a Noninvasive Method to Screen for Gastroesophageal Varices 
 
 
Principal Investigator: 
Andrew Smith MD PhD 
Vice Chair of Clinical Research and Associate Professor 
Director of Human Imaging Shared Facility (HISF) 
Chief of Body CT 
Oncologic and Abdominal Radiologist 
UAB Department of Radiology  
JTN 452, 619 19th Street South 
Birmingham AL 35249-6830 
(769) 610-6235 (cell) 
Email: andrewdennissmith@uabmc.edu 
 
Original Protocol:  
 
4/01/2019 
 
 
1. STUDY DESIGN / SUMMARY:  
 
Cirrhosis leads to portal hypertension and development of gastroesophageal varices, which are the 
most common cause for bleeding in cirrhosis and a major cause of death. The American Association for 
the Study of Liver Disease (AASLD) recommends screening endoscopy every 2 years to evaluate for 
gastroesophageal varices, and annual surveillance for those with small varices on endoscopy.  
Unfortunately, endoscopy is costly, requires sedation, is poorly tolerated, is subject to high inter-observer 
variability, and is associated with risks that include bleeding, esophageal injury and aspiration. 
Noninvasive methods for evaluation of gastroesophageal varices are needed. CT is noninvasive, rapid, 
less expensive than endoscopy, requires no sedation, provides a quantitative measure of the size of the 
varices, and allows for assessment of para-esophageal varices, varices in other body locations, ascites, 
other signs of portal hypertension, patency of liver vasculature, and detection, diagnosis and staging of 
hepatocellular carcinoma. Single-Energy CT (SECT) has relatively high accuracy in prospective studies 
for detection of any and large varices but is associated with suboptimal contrast opacification of 
gastroesophageal varices. Dual-Energy CT with the GE scanners with GSI Xtream (DECT) improves the 
contrast-to-noise ratio by 60% compared to SECT and is currently standard of care at UAB for evaluation 
of cirrhosis. The primary objective of this study is to determine the accuracy of DECT for detecting any 
varices and high-risk varices. We hypothesize that the accuracy (AUROC) of DECT will be >0.90 and 
>0.95 for detecting any and high-risk varices in a prospective pilot study (N=50) that uses endoscopy as 
the reference standard. This will be a single-center pilot observational prospective IRB-approved study. 
We will enroll 50 adult patients presenting to UAB Endoscopy for surveillance endoscopy to detect and 
grade gastroesophageal varices. 
 
 
2. BACKGROUND AND RATIONALLE 
 
Cirrhosis leads to portal hypertension and development of gastroesophageal varices, which are the 
most common cause for bleeding in cirrhosis and a major cause of death. Bleeding varices have a 6-
week mortality of 15%-25%.1,2 About 50% of patients with cirrhosis have varices, and 30% have large 
varices (>5 mm) that are high risk for bleeding.3 
The American Association for the Study of Liver Disease (AASLD) recommends screening 
endoscopy every 2 years to evaluate for varices, and annual surveillance for those with small varices on 
endoscopy.4 Patients at a high risk of bleeding with large varices, small varices and red wale signs (an 
endoscopic finding), or small varices and decompensated cirrhosis proceed to treatment such as 
prophylactic band ligation and beta blockers.5,6,7  Conversely, patients with no varices or small varices 
(≤5 mm) continue surveillance efforts by endoscopy to monitor for development of large varices.3,7,8 
Unfortunately, endoscopy is costly, requires sedation, is poorly tolerated, is subject to high inter-observer 

variability, cannot detect other signs or portal hypertension or para-esophageal varices that are at risk for 
future bleeding events, and is associated with risks that include bleeding, esophageal injury and 
aspiration.9 Many of these factors contribute to poor patient compliance with AASLD recommendations.  
Noninvasive methods for detecting, grading, and risk stratification of esophageal varices are needed. 
Imaging tests such as ultrasound elastography to measure liver stiffness have been proposed as a 
method to predict the presence of varices but have insufficient accuracy to eliminate the need for 
endoscopy.10  An ideal biomarker to screen for esophageal varices would be part of the routine standard 
of care of patients with cirrhosis, noninvasive, rapid, less expense than endoscopy, highly accurate, 
highly reproducible, and would require no sedation, provide a quantitative measure of the size of the 
varices, provide a mechanisms to assess the risk of future bleeding, allow for an assessment for other 
signs of portal hypertension, and provide other benefits to the patient (e.g. detect ascites and HCC and 
assess liver vasculature). 
Computed tomography (CT) is standard of care to screen for HCC. CT is noninvasive, rapid, less 
expensive than endoscopy, requires no sedation, provides a quantitative measure of the size of the 
varices, and allows for assessment of para-esophageal varices, varices in other body locations, ascites, 
other signs of portal hypertension, patency of liver vasculature, and detection, diagnosis and staging of 
HCC. Conventional Single-Energy CT (SECT) has relatively high accuracy in prospective studies for 
detection of any and large varices and has higher inter-observer agreement than endoscopy (kappa 0.56 
vs. 0.36, respectively).11 Major deficiencies in SECT include relatively suboptimal contrast opacification of 
gastroesophageal varices, inconsistent accuracy that is dependent upon SECT image acquisition 
technique, and suboptimal stratification of the risk of bleeding (e.g. inability to detect red wale sign) 
compared to endoscopy.  
Dual-Energy CT (DECT) improves the contrast-to-noise ratio by 60% compared to SECT. DECT also 
improves visualization by taking advantage of the markedly increased attenuation of iodine at photon 
energy levels just above the iodine K edge (33 keV). Using material decomposition techniques, DECT 
can map the concentration of iodine on a voxel by voxel basis which, combined with higher contrast to 
noise resolution on these same type of images, improves the conspicuity of enhancing structures. DECT 
is routinely used at the University of Alabama at Birmingham (UAB) to screen for HCC in cirrhotic 
patients. 
While DECT has been shown to improve image quality and portal venography compared to SECT, 
the accuracy of DECT for screening for varices has not been reported. 
 
 
3. OBJECTIVES 
 
 
3.1 
Primary Objective 
 
To determine the accuracy of dual energy CT for detecting any varices and high-risk varices 
in patients with cirrhosis presenting for upper gastrointestinal endoscopy. 
 
3.2 
Secondary Objectives 
 
3.2.1 To assess inter-observer agreement for the detection of any varices and high-risk varices 
on dual energy CT. 
 
3.2.2 To compare the accuracy of grade of varices on CT to grade of varices on endoscopy for 
predicting gastroesophageal variceal bleeding at 2 years.  
 
3.2.3 To develop and compare the accuracy of multivariate statistical models designed to 
predict 2-year risk of bleeding gastroesophageal varices, both without and with dual 
energy CT findings. 
 
3.2.4 To predict 2-year liver-related events using the variceal grade on DECT, LSN score and 
MELD score. 

 
4. PARTICIPANT SELECTION 
 
     This will be a single-center pilot observational prospective IRB-approved study. We will enroll 50 adult 
patients presenting to UAB Endoscopy for surveillance endoscopy to detect and grade gastroesophageal 
varices and follow up with patients for at least 2 years. These patients will present to the Highlands 
Gastroenterology Endoscopy Center or to the Kirklin Clinic Gastroenterology Endoscopy Center and will 
be seen by sub-investigator Omar Massoud MD, a hepatologist and gastroenterologist. Approximately 8 
to 10 patients per week are expected to meet final inclusion criteria, and we anticipate that we will 
approach 100 patients about study participation to accomplish 50 recruited patients over 9 months.  
 
4.1 
Inclusion Criteria 
 
Adult patients with cirrhosis presenting to UAB Endoscopy for surveillance endoscopy to 
detect and grade gastroesophageal varices 
 
4.2 
Exclusion Criteria 
 
4.2.1 Inability to provide written informed consent 
 
4.2.2 History of bleeding gastroesophageal varices, variceal intervention or portosystemic shunt 
 
4.2.3 Prior liver transplant 
 
4.2.4 History of malignancy 
 
4.2.5 Severe chronic kidney disease with estimated glomerular filtration rate (GFR) < 30 
mL/min/1.73 m2 
 
4.2.6 Presence of acute kidney injury 
 
4.2.7 Prior iodinated contrast allergy 
 
4.2.8 Patient weight >300 lbs 
 
4.2.9 Multiphasic liver CT within 3 months of upper endoscopy 
 
4.2.10 Pregnancy 
 
4.3 
Inclusion of all races and ethnic groups are eligible for this trial. There is no bias towards age 
or race in this trial. The trial is open the accrual of women and men. 
 
 
5. RECRUITMENT AND SCREENING 
 
5.1 
Recruitment Process 
 
Patients presenting to the Highlands Gastroenterology Endoscopy Center or to the Kirklin Clinic 
Gastroenterology Endoscopy Center will initially be approached by the hepatologist (Omar Massoud 
MD, sub-investigator who routinely performs surveillance endoscopy procedures) to ask if the patient 
would be interested in the study. If the patient is interested, the study coordinator will meet with the 
patient prior to endoscopy, answer questions, review the inclusion/exclusion criteria, and obtain 
informed consent. The study coordinator will review the labs, order any missing research study labs, 
and schedule the DECT exam. The patients will be directed to our outpatient facilities at Leeds or 

Gardendale, as both centers have a Dual Energy GE Revolution CT with GSI Xtream (DECT). After 
imaging, the patient will be given a $75 incentive for their time, and the patient will be discharged. 
Patients will provide consent for a follow up interview to evaluate for liver-related events, particularly 
bleeding varices. The study coordinator will arrange the interview and record all data in a secure 
web-based REDCap research database. 
 
5.2 
Screening Process 
 
The study coordinator will screen the endoscopy schedule daily to look for potentially eligible 
patients. The study coordinator will inform the gastroenterologist of potentially eligible patients.  
 
 
6. PROTOCOL PROCEDURES, METHODS, AND DURATION (LAYMAN’S DESCRIPTION) 
 
After confirmation of patient eligibility, the study coordinator will obtain written informed consent. 
The informed consent process may take up to 45 minutes. The study coordinator will review the labs, 
order any missing research study labs to calculate the FIB-4 index and MELD score, and schedule 
the DECT exam at a time that is convenient for the patient but within 2 weeks of the endoscopy. 
Women of childbearing potential will receive either a blood draw or urine pregnancy test to make sure 
they are not pregnant. Baseline clinical and laboratory data will be gathered by the study coordinator 
and entered into a REDCap database.  
The patient will undergo the upper gastrointestinal (GI) endoscopy procedure and recovery per 
standard of care. The endoscopy results (e.g. grade of esophageal varices) will be entered into the 
REDCap database. After the post-endoscopy procedure recovery period and prior to discharge, the 
study coordinator will complete a questionnaire with the patient to capture the patient’s experience 
and document any complications related to the upper GI endoscopy. The questionnaire will take 15 
minutes to complete. The questionnaire data will be entered into the REDCap database. The patient 
will be provided with the date and time of the scheduled DECT study, which may be on the same day 
as the endoscopy or within 2 weeks from endoscopy. The patients will be scheduled for DECT at 
Leeds or Gardendale, as both Imaging Centers have a Dual Energy GE Revolution CT with GSI 
Xtream, which is needed for this study. The patient will be discharged per standard of care, and the 
questionnaire data will be entered into the REDCap database by the study coordinator. 
One the day of the DECT imaging, the patient will have nothing by mouth to eat or drink for 4 
hours prior to the DECT exam. The patient will check in at the imaging center for their scheduled 
DECT exam. An intravenous line will be placed by the technologist, and the patient will undergo 
DECT imaging with intravenous iodinated contrast. CT imaging will be obtained in the late arterial 
phase using bolus tracking and in the portal venous phase using a dual energy CT approach. In 
order to reduce radiation dose, the noncontrast and delayed phases (present in a routine 4-phase 
liver CT) will not be obtained. The time from check in to completion of the imaging study is expected 
to be 45 minutes. After imaging, the study coordinator will complete a questionnaire with the patient 
to capture the patient’s experience and document any complications related to the CT imaging 
procedure. The questionnaire will take 15 minutes to complete. The patient will be given a $75 gift 
card incentive for their time, and the patient will be discharged. The questionnaire data will be 
entered into the REDCap database.  
The patients will be contacted by phone by the study coordinator at 1- and 2-years post 
endoscopy to capture information on complications of cirrhosis, particularly bleeding episodes and 
treatment of high-risk gastroesophageal varices. The phone interview is expected to take 15 minutes 
to complete. If the patient has a visit to the hepatologist, the interview may alternatively be conducted 
at that time per patient preference. The electronic medical records will also be searched for 
complication of cirrhosis and bleeding episodes. The study coordinator will conduct the interviews 
and record all data in a REDCap database. The patients will be discharged from the study after the 2 
year follow up interview.  
 
 

7. RISKS 
 
7.1 
Breach of Confidentiality – There is an unlikely potential risk of a breach of confidentiality.  
 
7.2 
Intravenous (IV) Catheter Placement - Participants may experience pain, bruising or bleeding 
at the IV catheter site. There is a very small risk for developing an infection.  
 
7.3 
Contrast Injection – Patients will receive FDA-approved iodinated contrast (dye) through an 
IV-line during the dual energy CT scan. The contrast is essential for improving visualization of 
varices. There is a small risk of IV-line infiltration. Immediately following injection, patients 
may feel a mild warm feeling that will go away in a few seconds. Uncommon side effects 
include physiologic reactions and allergic-like reactions such as abnormal heart rate, nausea, 
dry mouth, itching, hives, cough, or shortness of breath. Very rarely, people can experience 
life-threatening allergic reactions to iodinated contrast. The CT contrast dye can rarely cause 
kidney injury in patients who already have severe kidney disease. 
 
7.4 
Radiation – Study participants will be exposed to radiation from the DECT imaging. There is 
an extremely low risk that the radiation may cause cancer or other radiation effects years after 
the study. Exposure to the radiation through this study is not part of routine healthcare. 
 
7.5 
Risk of an Unexpected Imaging Finding – There is a risk that an unexpected imaging finding 
could be detected. In many cases, these are of benefit to the patient, such as detection of a 
unexpected cancer. In some cases, the unexpected finding may be indeterminate, such as a 
renal mass that is not clearly benign or malignant. Indeterminate findings may need additional 
workup that will not be covered as a part of this study. 
 
 
8. PRECAUTIONS / MINIMIZATION OF RISKS 
 
Participants will be monitored by study personnel for risks—physical, psychological, social, 
economic, and/or legal—that participants may encounter during their participation in this study 
or as a result of DECT imaging and data collection required in this protocol.  
 
8.1 
Breach of Confidentiality – The research team is experienced and will utilize best practices to 
avoid a breach of confidentiality.  The risk of confidentially will be minimized by collecting only 
the data that is required by the study, labeling all data forms and samples with a coded 
identifier, and maintaining all study records in locked files or password-protected computer 
files. 
 
8.2 
Intravenous (IV) Catheter Placement - The radiology technologists are experienced with IV-
line placement and will utilize best practices to minimize pain and avoid bruising, bleeding, 
and infection. 
 
8.3 
Contrast Injection – A power injector will be used to assist with detecting IV-line infiltration. 
The radiology technologists are trained to manage physiologic and allergic-like reactions, and 
there is a physician available for more severe reactions. Kidney function will be tested in all 
participants through a blood draw prior to the receiving the contrast. Patients who have had a 
prior allergic reaction or have severe kidney disease cannot participate in this study. All 
patients will be monitored for reactions during this study. 
 
8.4 
Radiation – The total radiation exposure is expected to be 16 mSv, equivalent to about 2.6 
years of exposure to natural background radiation. Background radiation is radiation normally 
received from sources such as cosmic rays and natural radioactivity in building materials and 
the ground. Exposure to the radiation through this study is not part of routine healthcare. The 

amount of radiation exposure has been minimized by the research doctors. For example, a 
normal liver CT for evaluation of cirrhosis includes 4 different scans of the liver, but this 
research scan only include 2 scans of the liver and therefore half the amount of radiation. 
 
8.5 
Risk of an Unexpected Imaging Finding – All of the research DECT liver CTs will be 
interpreted by a radiologist, a physician with expertise in CT imaging. A formal report will be 
placed permanently in the electronic medical records. Clinically significant unexpected 
imaging findings will be communicated by phone with the gastroenterologist, per standard of 
care at UAB.   
 
 
9. BENEFITS 
 
The dual energy CT scan will be interpreted by a radiologist, a physician with expertise in CT 
imaging. A formal report will be placed permanently in the electronic medical records. It is possible 
that the radiologist may detect liver cancer or another important but unexpected finding. Clinically 
significant unexpected imaging findings will be communicated by phone with the gastroenterologist 
per standard of care at UAB. The gastroenterologist will discuss these findings with the participants. 
 
 
10. ALTERNATIVES 
 
This is not a treatment study. The alternative is to not participate in this study. 
 
 
11. DATA AND IMAGE ANALYSIS 
 
11.1 
Clinical Evaluation:  
     
Baseline clinical and laboratory 
data (Table 1) will be gathered by 
the study coordinator and entered 
into a password-restricted and 
secure web-based REDCap 
database. Data from the post-
endoscopy and post-DECT 
questionnaires will be entered into 
the REDCap database.  
 
 
11.2 
Endoscopy Evaluation: 
 
All patients will undergo standard of care upper gastrointestinal endoscopy in The Kirklin Clinic or 
Highlands Hospital endoscopy suites for surveillance of gastroesophageal varices. The endoscopists 
will report the grade of esophageal varices: grade 0 = none, grade 1 = small (≤5 mm), and grade 2 = 
large (>5 mm). The endoscopists will also record the presence or absence of a red wale or red spot 
sign, presence or absence of gastric varices, presence or absence of signs of portal gastropathy, 
presence or absence of gastritis, duodenitis, or a gastric or duodenal ulcer, and presence or absence 
of active bleeding (and location if present). The hepatologist will also be contacted to confirm the 
substage of cirrhosis, which includes the information from the surveillance endoscopy. 
 
11.3 
Image Evaluation:  
 
11.3.1 DECT Image Acquisition: 
Table 2. Relevant Clinical and Laboratory Data  
• Demographics: age, gender, race, ethnicity, body mass index 
• Comorbidities:  Charlson comorbidity index 
• Cirrhosis etiology: AH, HBV, HCV, NAFLD, cryptogenic, 
autoimmune, and other 
• Baseline cirrhosis substage: compensated without varices, 
compensated with varices, and decompensated 
• Baseline serum labs: total bili, AST, ALT, albumin, INR, 
platelets, creatinine, calculated MELD and FIB-4 scores 
• Study procedure date: date of endoscopy and DECT 
• Procedure complications: From DECT or endoscopy 
• 2-year follow up to track liver-related events: ascites, hepatic 
encephalopathy, bleeding varices, intervention for varices, TIPS, 
liver transplant, HCC, or death 

 
Study participants will undergo DECT imaging of the liver in the late arterial and in the portal 
venous phases. The late arterial phase will be performed with bolus tracking and occur 20 seconds 
after triggering. The portal venous phase will also be performed with bolus tracking and occur 40 
seconds after triggering. Both phases will utilize our standard-of-care DECT image acquisition 
protocol. Imaging will be performed per standard of care, with the patient in the supine position with 
arms above the head. No oral contrast will be administered. Noncontrast and delayed phase 
imaging will not be performed to reduce the radiation dose.  
 
11.3.2 DECT Image Evaluation: 
 
The DECT images will be interpreted according to our standard of care with a dictated report by 
a board-certified abdominal radiologist. The radiologist interpreting the study will be asked to 
interpret the study using a structured reporting template that includes the grade of esophageal 
varices, presence or absence of other varices, presence or absence and stage of HCC, severity of 
ascites, and patency of liver vasculature. The structured report template is currently in use by 
multiple abdominal faculty and can be easily acquired by any abdominal radiologist at UAB through 
Powerscribe, our routine dictation reporting system.  
Each DECT study will be de-identified per standard technique using OsiriX. A coded identifier 
will be applied to each image, and the images will be stored on OsiriX and on a secure password-
restricted Server Message Block (SMB), a virtual hard drive established for Radiology Clinical 
Research that has restricted access to defined users. Study personnel will use the Liver Surface 
Nodularity (LSN) Software to measure the LSN score on all patients, while remaining blinded to the 
clinical data. Dr. Smith or Dr. Morgan will review all of the exported images and confirm a 
satisfactory measurement for each patient, with revising of measurements that are not satisfactory. 
 
11.3.3 Inter-observer Analysis: 
 
After all patients are recruited (N=50), a designated co-investigator will set up reading session for 
the other radiology co-investigators (N=4 radiology residents and N=4 radiology faculty). A training 
video will be prepared and used to instruct the readers on how to view the images, conduct the 
reading sessions, and record the data in a REDCap.  
Each reader will interpret the images independently in timed reading sessions, while blinded to 
clinical data. The most important data point will be the grade of esophageal varices, though readers 
will also evaluate for presence or absence of other varices, presence or absence and stage of HCC, 
severity of ascites, and patency of liver vasculature. 
 
 
12. 2-YEAR FOLLOW UP: 
 
The primary purpose of screening for gastroesophageal varices is to prevent future variceal 
bleeding and the associated high mortality. Detection of bleeding events is therefore a critical 
component of the study. The patients will be contacted by phone by the study coordinator at 1- and 
2-years post endoscopy to capture information on complications of cirrhosis, particularly bleeding 
episodes and treatment of high-risk gastroesophageal varices. If the patient has a visit to the 
hepatologist, the interview may alternatively be conducted at that time per patient preference. The 
electronic medical records will also be searched for complication of cirrhosis and bleeding episodes. 
The study coordinator will conduct the interviews and record all data in a REDCap database. The 
patients will be discharged from the study after the 2 year follow up interview.  
 
 
 

 
13. STATISTICAL CONSIDERATION: 
 
13.1 Sample size justification 
 
Yufeng Li PhD (co-investigator and biostatistician) will conduct and supervise all statistical analyses.  
This is a prospective study to determine the accuracy of dual energy CT for detecting any varices and 
high-risk varices in patients with cirrhosis presenting for upper gastrointestinal endoscopy. The endpoint 
of the primary objective is accuracy which is determined by the Area Under the Curve (AUC) using 
Recursive Operating Characteristics (ROC) analysis (AUROC).  Based on published studies 1,2,3 in 
patients with detected gastroesophageal varices, we will observe 32%, 32%, and 36% with no, small, 
and large varices, respectively. In order to test the hypothesis: the accuracy (AUROC) of DECT will be 
>0.90 for detecting any and high-risk varices in a prospective pilot study that uses endoscopy as the 
reference standard, we plan to enroll 50 patients such that we will have 16/50, 16/50, and 18/50 with no, 
small, and large varices.  This size of the study will have >95% power to detect any varices, e.g. 
(16+18)/50 small and large varices with AUC >=0.90 comparing to null hypotheses of AUC=0.5 (not 
detect any) using a one-sided z-test at a significance level of 0.05 controlled false positive rates at 1%.  
  
13.2 Statistical analysis plan 
 
Patient and imaging characteristics will be summarized and compared using appropriate 
summary statistics, e.g. mean and standard deviation for continuous variables, frequency and 
percentage for categorical variables, and extensive exploratory data analysis and data visualizations 
will be utilized to assess diagnostics, identify outliers, and validate assumptions.  
Receiver operating characteristic (ROC) analysis will be used in Aim1 to estimate the accuracy of 
DECT for differentiating no varices from any varices and for differentiating no and small varices from 
large varices in Aim 1. Sensitivity, specificity, accuracy, and AUC along with their two-sided 95% CI 
will be presented separately. The grade of varices (0, 1, 2) on DECT will be correlated with the grade 
of varices on endoscopy (0, 1, 2) using weighted Kappa coefficient for categorical data (Aim 2.2).   
The MIXED effect model will be used in Aim 2.1 to estimate the ICC for the inter-observer 
agreement for the detection of any varices and high-risk varices on dual energy CT. Reader 
experience and subject will be the two random effects in the model used for interobserver variability. 
The intraclass correlation coefficient (ICC) will be defined as the ratio between subject variance and 
the sum of variances for subject, reader experience and error term. ICC values will be characterized 
as very poor (0 to <0.20), poor (0.20 to <0.40), moderate (0.40 to <0.60), good (0.60 to <0.80), and 
very good (0.80 to 1.00).   
Time to development of bleeding varices (or hepatic event) will be modeled in Aim 2.3 using Cox 
proportional hazards models with clustered sandwich estimators to account for within and between 
cluster correlations. Cause specific proportional subhazards analysis while accounting for competing 
risks (e.g. gastroesophageal banding) and adjusting for covariates will be utilized to assess the 
association between endoscopic findings and DECT findings and time to developing individual vs. 
any hepatic complications. 
A combination of variceal grade on DECT, LSN score and MELD score will have equal or greater 
accuracy for predicting 2-year liver-related events than a combination of endoscopic findings and 
MELD score. This analysis will be exploratory in Aim 2.4, but a trend may be evident and justify 
further investigation. Competing risks analysis will be used to assess the association of variceal 
grade on DECT, LSN score and MELD scores with development of liver-related events, with specific 
attention to 2-year variceal bleeding events. Cumulative Incidence Function (CIF) will be used to 
estimate the marginal probability of a liver-related event as a function of its cause-specific probability 
and overall survival probability.  
 
All analysis will be carried out using SAS v 9.4.