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...
Introducing a groundbreaking research technology, the The Digestive Health Foundation became a founding supporter in 2017 of a powerful new resource for digestive health medical research: The Digestive Health Foundation BioRepository. As one of only a few GI biorepositories of its kind in the world, the DHF BioRepository stores, organizes, and makes accessible (digitally, in real time) blood and tissue samples from patients and family members diagnosed with one or more of the digestive disorders treated at the Northwestern Medicine Digestive Health Center. Digestive disease research using the DHF BioRepository will leverage the latest advances in information technology with cutting-edge biologic and molecular research techniques to better understand gastrointestinal diseases and to help develop better treatment options for patients. Across GI sub-specialties, from liver and pancreatic cancers, esophageal diseases/swallowing disorders, inflammatory bowel disease (Crohn’s Disease and ulcerative colitis), GERD, IBS, bariatric surgery, nutritional issues, and many more, the extensive and growing patient network at Northwestern Medicine provides a diverse and valuable resource of participants. After a patient chooses to participate, Northwestern Medicine directly links the patient’s anonymized electronic medical record, physiologic diagnostic test results, imaging results, and patient-directed quality of life indicators to a tissue bank that will include: samples obtained during endoscopy (biopsies), blood, urine, and stool. The DHF BioRepository’s depth of capacity will enable physician scientists around the world to pursue large scale research studies into the mechanisms of digestive diseases. Discoveries about the natural history and progression of digestive disease is providing the insight necessary to develop new diagnostic tools, better treatments, and eventual cures for digestive disease patients and future generations. — The Digestive Health...
Principal Investigator: Mary Rinella, MD The most common cause of liver injury in the United States, non-alcoholic fatty liver disease (NAFLD) occurs when extra fat builds up in liver cells. A serious offshoot of NAFLD, nonalcoholic steatohepatitis (NASH) can cause the liver to become inflamed. Those who develop NASH often require a liver transplant. Even after liver transplant, these patients face an uphill battle. They remain at particularly high risk of NASH recurrence, which can lead to graft failure and even death. Currently painful and invasive needle biopsies are the only way to diagnose and stage NASH. As NASH reoccurs, byproducts of the disease process appear in the blood that may provide important clues to disease progression. Supported by a grant from the Digestive Health Foundation, Mary Rinella, MD, a gastroenterology and hepatology faculty member and her co-investigators hope to develop a blood-based alternative by identifying biomarkers that can accurately indicate the onset or recurrence of NASH. The investigators will focus on patients who have undergone liver transplantation at Northwestern Memorial Hospital from 1987 to present. Their pilot study will look at participants from the “Mini-Liver” cohort: patients who have had liver biopsy after transplantation, several of whom have recurrent NASH. Plasma samples are collected from all patients in this group and immediately stored at the time of biopsy for future reference and research studies. Dr. Rinella’s study will involve the use of a validated blood serum-based biomarker panel test (OWLiver assay) that has shown great promise in diagnosing NASH in the non-transplant setting to test the existing biobanked plasma samples. The researchers will also review clinical data drawn...
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...
