3 Clinical Trials for Various Conditions
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.
The goal of this research is to validate novel non-invasive Magnetic resonance imaging (MRI) biomarkers to detect Gastroesophageal varices (GEV) in patients with cirrhosis, including fractional flow change in the portal vein and elevated azygos flow. End-stage liver disease (cirrhosis) is characterized by advanced fibrosis, liver failure, and portal hypertension. There are many causes of cirrhosis, including viral hepatitis, alcohol abuse, and perhaps most importantly, non-alcoholic fatty liver disease (NAFLD) and its aggressive subset, non-alcoholic steatohepatitis (NASH). 3 million new cases of end-stage liver disease (cirrhosis) are expected over the next decade. In cirrhosis, portosystemic collaterals that shunt blood away from the liver develop due to increased portal pressure. Gastroesophageal varices (GEV) are the most clinically relevant because they can cause fatal internal bleeding. GEV bleeding carries \~20% mortality at 6 weeks, and \~34% overall mortality. Identification of at-risk varices, prior to bleeding, is of paramount importance to initiate primary prophylaxis. To identify and treat at-risk patients, current guidelines recommend regular esophagogastroduodenoscopy (EGD) and variceal band ligation. Detection of high-risk GEV is key to initiating primary prophylaxis, which can reduce mortality by 50-70%. However, endoscopy is invasive and often unnecessary when no treatment is required. Therefore, the American Association for the Study of Liver Diseases has identified the development of "non-invasive markers that predict the presence of high-risk varices" as a major unmet need.
The natural history of cirrhosis has a symptomatic and asymptomatic stage. The symptoms include the development of ascites, hepatic encephalopathy, or variceal bleeding. The development of portal hypertension represents a critical transition point in the natural history of cirrhosis, contributing to, or directly responsible for all of these events. It is defined by an increase in intrahepatic vascular resistance to portal venous inflow, with the subsequent development of collateral vessels, such as esophageal or gastric varices. As portal pressures rise over time, however, the resulting increase in variceal size and wall tension translates into an increasing likelihood of rupture and bleeding, leading to death in about 30% of patients. Over the last twenty years, data have emerged regarding the role of tumor necrosis factor (TNFα) in portal hypertension from animal models as well as in vitro experiments. Portal hypertension is a condition characterized by vasodilatation and a hyperdynamic circulation, driven by relative overproduction of nitric oxide23. In animal trials using inhibitors of TNF it has been shown to decrease the development of the hyperdynamic circulatory state and portal pressure.24-25 Based on these data, investigators have examined the role of TNF inhibition with thalidomide. Significant improvement in blocking the development of the hyperdynamic circulation and portal pressures was demonstrated.26 Human trials have also show the efficacy of thalidomide in reducing portal pressures. In that these trials have shown promising results further investigation is