Principal Investigator: Josh Levitsky, MD, Professor of Medicine (Gastroenterology and Hepatology), Medical Education and Surgery (Organ Transplantation), Northwestern University Feinberg School of Medicine Autoimmune hepatitis (AIH) occurs when the body’s immune system attacks its own liver cells, causing long term scarring and damage to the liver. No one knows precisely what causes autoimmune hepatitis (AIH), but it is diagnosed more frequently in patients with other autoimmune diseases (e.g., celiac disease, ulcerative colitis, rheumatoid arthritis, etc.) and in women, and often begins in adolescence or young adulthood. Standard treatment focuses on suppressing the immune system with medications, yet immunosuppressants have many potentially harmful side effects. General recommendations call for patients to stop taking the medications when they are no longer needed. Unfortunately, without them, most patients soon relapse and risk more liver injury. Currently, tracking relapses requires taking a biopsy of the liver—a very invasive procedure—and looking at it under the microscope. The Levisky lab believes that measuring levels of biomarkers in the blood may offer a less invasive window into the liver than a traditional biopsy, giving physicians the ability to predict AIH relapse before the liver incurs any damage. This project offers the potential for better monitoring of patients with AIH. It also may shape the future of personalized treatments to individualize immunosuppressant therapy by using simple, cost effective blood draws rather than riskier liver...
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...
Principal Investigator: Josh Levitsky, MD | Co-Principal Investigator: Imran Nizamuddin, MD Primary sclerosing cholangitis (PSC) causes chronic inflammation of the bile ducts and, over time, potential liver failure. What triggers PSC and how it is strongly linked to ulcerative colitis (UC) remains unclear. One theory is that a “leaky gut” allows toxic compounds from the intestines to erroneously enter the liver. Dr. Levitsky’s team intends to test this theory by measuring intestinal permeability in PSC patients. Intestinal permeability (leakiness) can be studied by comparing absorption of different simple sugar solutions. Study participants will drink several sugar solutions to compare absorption and elimination in the urine. Researchers anticipate that the sugar levels in the urine will be different between patients with PSC, patients with PSC and ulcerative colitis, and healthy patients. If this occurs, the team will evaluate therapies, such as antibiotics, to assess their impact on the “leaky gut.” This project may serve as an initial step toward developing personalized treatment options for patients who currently don’t have any therapeutic options—currently a high unmet need in the field of...
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: 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...
