Principal Investigator: Daniel Ganger, MD; Co-Principal Investigator: Justin R. Boike, MD Chronic liver disease remains a significant burden on society, despite the ability to treat and cure hepatitis C. With the growing obesity epidemic in the United States, fatty liver disease will soon overtake hepatitis C as the primary cause of chronic liver disease and cirrhosis. While liver transplantation offers a cure, it is not an option for many individuals who face complications of cirrhosis such excessive fluid retention and internal bleeding. Transjugular intrahepatic portosystemic shunt (TIPS) procedures offer an effective tool for treating these complications. In some patients, though, TIPS can worsen liver failure and sometimes cause debilitating confusion called hepatic encephalopathy. It is believed that excessive shunting of blood flow from the liver may be the culprit. In this study, the researchers will study the ability of a new laboratory test to measure the percentage of blood shunted away from the liver to better predict those patients at greatest risk for hepatic encephalopathy after a TIPS procedure. This tool could dramatically help guide the use of TIPS and promote earlier use of TIPS in low-risk...
Principal Investigator: Nikhilesh Mazumder, MD, MPH Severe damage to the liver can profoundly affect a variety of body systems. Patients with cirrhosis suffer from excess fluid in the legs, abdomen, and chest. Medications can reduce fluid buildup but dosing is not an exact science. Inaccurate dosing can harm the kidneys, cause confusion, and even land patients in the hospital. To avoid these complications, clinicians rely on a multitude of blood and imaging tests that often require expensive equipment, drawing blood, or specially trained staff. Dr. Mazumder’s team seeks to simplify the process by testing the benefit of a decades-old technique called the Valsalva maneuver in combination with a finger photoplethysmography device (similar to a noninvasive bedside pulse oximeter). Patients hold their breath for 10 seconds, and the device measures changes in blood flow to the finger. Safely and successfully tested in individuals with heart problems to predict levels of fluid overload, the...
Principal Investigator: Richard M. Green, MD A chronic bile duct and liver disease, Primary Sclerosing Cholangitis (PSC) affects more than 50,000 Americans and can progress to cirrhosis, liver failure, and bile duct cancer. Currently, the only effective therapy is liver transplantation. Better understanding the pathogenesis of PSC is urgently needed to develop new therapies. In recent cell culture and animal studies, Dr. Green and his colleagues focused on a protective cell signaling pathway: the unfolded protein response (UPR). They found that the UPR is activated when bile flow is impaired, and mice lacking UPR genes in their liver are highly susceptible to injury from bile duct obstruction. Now moving forward with the first human investigations examining UPR, Dr. Green aims to determine how it is activated in the bile ducts of patients with PSC. The team plans to study bile duct tissues obtained during endoscopic procedures performed for bile duct obstruction. The identification of “protective” genes and proteins could lead to new drug targets and, ultimately, the development of novel medical...
Principal Investigator: Daniel R. Ganger, MD Many babies born with heart problems grow up and mature well into adulthood thanks to modern surgical advancements. In fact, one million adults currently live with some form of congenital heart disease in the United States alone. A rare congenital heart condition, single ventricle disease usually requires surgical intervention early on, with most children undergoing a common surgery known as the Fontan procedure. While it helps these young patients to overcome their heart problem, unfortunately the Fontan procedure can lead to liver problems—from cirrhosis and liver cancer to even liver failure—over time. Even with this knowledge, current hepatic laboratory testing, imaging tools, and/or liver biopsies are woefully inaccurate predictors of the development of serious liver disease. Awarded a grant from the Digestive Health Foundation, Northwestern Medicine investigators see a potential solution to providing effective screening and treatment for this chronically-ill population: the HepQuant-SHUNT test. Safe and non-invasive, the HepQuant-SHUNT test has shown promise by yielding easily reproducible and accurate measurements of liver function. In studies involving Hepatitis C patients, the novel test has begun demonstrating its strength for predicting important hepatic clinical outcomes, including liver-related death. Outdoing the results of the current gold standard of care, invasive liver biopsy, the HepQuant-SHUNT test may offer a more accurate as well as tolerable test for patients. GI and hepatology faculty member Daniel R. Granger, MD and chief medical resident Alexander Lemmer, MD, hope to determine if the HepQuant liver function test can accurately predict significant hepatic clinical outcomes in the post-Fontan population. Recruiting a total of 50 Fontan patients (ages 18-65) from Northwestern Memorial Hospital...
