Decreasing Risk of Life Saving TIPS Procedure in Liver Failure Patients

Principal Investigator: Lisa B. VanWagner MD, MS, Assistant Professor of Medicine (Gastroenterology and Hepatology) and Preventive Medicine (Epidemiology) Cirrhosis of the liver affects millions of Americans and leads to increased and life-threatening pressure in the blood vessels of the liver. One of the core treatments for this potentially deadly complication is a procedure called “TIPS.” While effectively reducing pressure in the liver, TIPS can result in heart failure in at least 20% of patients. The ability to identify patients at risk for cardiac dysfunction would allow clinicians to put into place targeted prevention strategies before and after TIPS. With that aim in mind, the VanWagner team is evaluating new imaging methods of the heart and liver to better understand how TIPS alters liver hemodynamics and changes cardiovascular structure, function, and flow in patients with cirrhosis undergoing TIPS. Study findings could lead to interventions to prevent the development of heart failure in this at-risk patient population, so more patients facing liver cirrhosis could safely receive the TIPS treatment while reducing the associated risk of heart...

Pediatric Liver Cell Response in Diseases that Cause Jaundice and Liver Failure

Principal Investigator: Alyssa Kriegermeier, MD Children with liver disease frequently suffer from jaundice caused by the poor flow of bile from the liver to the intestines—a disease state called cholestasis. Currently no treatments are available that effectively prevent liver failure due to pediatric cholestatic liver diseases. Lifesaving liver transplantation is often the only answer. Cells within the liver deal with the stress from cholestasis via stress-induced pathways known as the unfolded protein response (UPR). While the UPR has been studied in adult liver diseases, little is known about its activation in children. Dr. Kriegermeier previously demonstrated, in an animal model of primary sclerosing cholangitis (PSC), one form of cholestatic liver disease affecting children and adults (about 80 percent of whom also have inflammatory bowel disease (IBD- Crohn’s disease, ulcerative colitis, etc.)), that removing parts of the UPR affects disease progression. This study will seek to better understand the differences in adults and children within this cell stress response during times of cholestasis. Identifying new therapeutic targets will provide a springboard for developing treatments for these children that will hopefully prevent them from needing liver...

Novel Protective Mechanism against Liver Damage in Liver Transplant Patients

Principal Investigator: Xiaoying Liu, PhD The term cholestasis describes any condition that impairs normal bile flow from the liver into the bile ducts and then into the intestine. This disease state can cause chronic liver damage, cirrhosis, end-stage liver disease (requiring a liver transplant), and death. Cholestatic liver diseases include primary sclerosing cholangitis (PSC) and primary biliary cholangitis (PBC). Cholestasis also occurs frequently after liver transplantation, which can result in the need for repeat liver transplantation or death. Unfortunately, the molecular drivers of cholestasis are still poorly understood with few effective medical therapies. The liver unfolded protein response (UPR) is a molecular pathway that protects cells from injury. UPR has been demonstrated to be important in many liver diseases, although its role in cholestasis remains unknown. Dr. Liu intends to investigate the activation of the liver UPR pathways in liver transplant patients with cholestasis. Identifying new UPR protein and gene targets will ultimate aid in developing novel drug therapies and improving liver transplant...

Evaluating a novel endoscopic ultra sound-guided technique for tissue acquisition for diagnosing pancreatic tumors

Principal Investigator: Sri Komanduri, MD, MS, FASGE, AGAF; Co-Principal Investigator: Robert Schenck, MD The thought of potentially having cancer is stressful enough without undergoing an invasive biopsy to diagnose it and finding out that the procedure needs to be repeated due to inadequate sample collection. This project aims to optimize strategies for acquiring tissue samples to assist gastroenterologists (and pathologists) in diagnosing many diseases, including cancers. Relying on endoscopic ultrasound guidance, the two methods currently utilized are fine needle aspiration, which is the gold standard, and a new method called fine needle biopsy. Drs. Komanduri and Schenck are conducting the largest study to date to compare these different strategies. After collecting data from patients who have undergone one of these procedures over a five-year period, the investigator will perform advanced statistical modeling to determine the strategy that best optimizes patient outcomes (including obtaining accurate diagnoses and minimizing repeat invasive procedures) and costs. Once identified, this strategy will ultimately be implemented throughout the Northwestern Digestive Health Center to enhance patient...

Impact of an artificial liver shunt procedure for the treatment of high pressure in the vein that carries blood from the digestive organs to the liver on the function of the heart

Principal Investigator: Lisa B. VanWagner, MD The portal vein carries blood from digestive organs to the liver. Portal hypertension occurs when pressure increases within this vein due to blockage in blood flow through the liver. Cirrhosis, or scarring, of the liver is the most common cause.  This condition often results in fluid build-up in the abdomen and bleeding from veins in the esophagus that can impair quality of life and even lead to death due to intestinal bleeding or infection. An artificial shunt procedure known as TIPS (transjugular intrahepatic portosystemic shunt) helps reduce portal hypertension. It works by connecting two veins: the portal vein that carries blood from the digestive organs to the liver and the hepatic vein that carries blood from the liver to the right part of the heart. While the lifesaving procedure may cause heart failure in some patients because of increased blood flow directly to the heart, others experience improvement in heart function. However, predicting outcomes for these patients is currently unknown. Dr. VanWagner’s study aims to better understand changes in heart function after a TIPS procedure to better intervene and prevent heart failure in these at-risk...