Dual Energy CT as a Noninvasive Method to Screen for Gastroesophageal Varices
Dual Energy CT as a Noninvasive Method to Screen for Gastroesophageal Varices
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.
 The study hypothesis is 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. A total of 50 adult patients presenting to UAB Endoscopy for surveillance
 endoscopy to detect and grade gastroesophageal varices will be enrolled.
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%. About 50% of patients with cirrhosis have varices, and
 30% have large varices (>5 mm) that are high risk for bleeding.

 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. 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. Conversely,
 patients with no varices or small varices (≤5 mm) continue surveillance efforts by endoscopy
 to monitor for development of large varices. 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. 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). 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 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. The primary objective
 is 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.
Inclusion Criteria:

 -  Adult patients with cirrhosis presenting to UAB Endoscopy for surveillance endoscopy
 to detect and grade gastroesophageal varices

 Exclusion Criteria:

 -  Inability to provide written informed consent

 -  History of bleeding gastroesophageal varices, variceal intervention or portosystemic
 shunt

 -  Prior liver transplant

 -  History of malignancy

 -  Severe chronic kidney disease with estimated glomerular filtration rate (GFR) < 30
 mL/min/1.73 m2

 -  Presence of acute kidney injury

 -  Prior iodinated contrast allergy

 -  Patient weight >300 lbs

 -  Multiphasic liver CT within 3 months of upper endoscopy

 -  Pregnancy

 -  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.