Genetic Mapping Offers Unprecedented Prevention and Treatment of Bile Duct Disorder, PSC

THIS STUDY UTILIZES THE DHF BIOREPOSITORY Principal Investigator: Xiaoying Liu, PhD, Research Assistant Professor of Medicine (Gastroenterology and Hepatology), Northwestern Medicine, Northwestern Feinberg School of Medicine A rare liver disorder, primary sclerosing cholangitis (PSC) occurs when thickening of bile ducts block the normal, necessary flow of bile within the digestive system. Buildup of toxic bile acids can lead to irreversible liver cirrhosis, cancer, and the need for a risky, life-altering liver transplant. For unknown reasons, up to 70% of patients with PSC also have inflammatory bowel disease (IBD), especially ulcerative colitis. Today, effective treatments don’t yet exist to prevent this progressive and potentially fatal liver disease. Dr. Xiaoying Liu’s team is using this year’s DHF grant award to better understand the disease process of PSC in order to stop it from damaging the liver. The researchers are studying a molecular pathway called “unfolded protein response (UPR)” that springs into action to protect cells from toxicity in the liver. This exciting study stands on the shoulders of previously successful DHF funded research proving increased UPR pathway gene expression in post-liver transplant patients. Dr. Liu hopes to further delineate the protective role of UPR to create a first-in-the-world liver cell atlas in PSC to map cell signaling and cellular interactions. These studies offer important promise for identifying molecular targets to develop much needed new drug therapies for PSC...

Earlier Detection for Alcohol-Associated Liver Disease Can Save Lives

THIS STUDY UTILIZES THE DHF BIOREPOSITORY Principal Investigators: Amanda C. Cheung, MD, Assistant Professor of Medicine (Gastroenterology and Hepatology), Northwestern Medicine, Northwestern Feinberg School of Medicine Andres Duarte-Rojo, MD, PhD, Professor of Medicine (Gastroenterology and Hepatology) and Surgery (Organ Transplantation), Northwestern Medicine, Northwestern Feinberg School of Medicine A serious public health concern, excessive alcohol consumption causes almost 50% of liver disease deaths in the United States. Unfortunately, many patients with alcohol-associated liver (ALD) damage have late stage disease by the time they receive a diagnosis. A major liver transplant is often their only option for lifesaving treatment. Importantly, the relationship between amounts of alcohol consumed and damage to the liver is difficult to predict, with some patients (often women) developing liver scarring earlier with less alcohol consumption while others are able to drink more without significant health complications. To add to this challenge, no detection tests currently exist to identify early signs of liver scarring (fibrosis) in individuals with alcohol use disorder. This year, a DHF award is supporting Dr. Amanda Cheung’s team in identifying a biomarker for early fibrosis to improve ALD screening for at-risk individuals. A network of proteins and molecules surrounding cells, the extracellular matrix (ECM) may offer promise as an early warning system. Inflammation from ALD has been shown to damage the ECM, increasing detectable chemical changes, or “degradome,” that are precursors to developing irreversible fibrosis. Up to this point, limited studies have looked only at the degradome profiles in the blood of patients with liver fibrosis. In this new DHF study, Dr. Cheung’s team is investigating the degradome profiles of patients with ALD before...

Personalized Exercise Program Improves Survival Rate in Liver Transplant Patients

Principal Investigator: Daniela P. Ladner, MD, MPH, Interim Director, Comprehensive Transplant Center; Professor of Surgery (Organ Transplantation) and Medical Social Sciences, Northwestern University Feinberg School of Medicine Patients with poor physical conditioning who are diagnosed with cirrhosis frequently experience worse outcomes before and after receiving a liver transplant. Exercise helps reduce frailty and leads to better outcomes, but patients face a variety of financial and logistical barriers to the regular physical activity needed to maintain strength. Additionally, transplant teams often expect patients to optimize their physical health on their own with little guidance. The Ladner research team seeks to optimize patient outcomes through a practical and affordable approach to enhance physical conditioning in the pre- and post-liver transplant setting. The researchers are developing a simple and cost-effective intervention called LIFT (Liver FrailTY), which will include a full in-person strength assessment, an exercise program with smart phone guidance, and remote coaching. Regular and frequent check-ins will be essential to encouraging patients to achieve recommended levels of exercise. Dr. Ladner’s study will then measure the impact of LIFT on strength as well as on positive clinical outcomes, such as increased survival and fewer hospitalizations for patients facing liver...

Predicting Relapse in Liver Failure (Autoimmune Hepatitis) Patients for Personalized Treatment

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...

Diagnosing Life Threatening Liver Disease (GALD) in Newborns Improves Chance of Survival

Principal Investigator: Sarah Taylor, MD, Assistant Professor of Pediatrics (Gastroenterology, Hepatology, and Nutrition), Ann & Robert H. Lurie Children’s Hospital of Chicago, Northwestern Medicine, Feinberg School of Medicine  Gestational alloimmune liver disease (GALD) is the leading cause of liver failure in newborns. This disease occurs when maternal antibodies injure the liver of the fetus during pregnancy. Infants with GALD require prompt diagnosis and treatment at birth. Even with treatment, about 50% of infants with GALD do not survive. Quickly obtaining a precise and reliable diagnosis remains challenging. DHF’s grant is enabling Dr. Taylor’s lab to create histologic scoring criteria that can be easily disseminated to enable prompt and reliable diagnosis of GALD. Evaluating the ribonucleic acid (RNA) of livers from affected patients, the Taylor team hopes to identify new blood tests that will differentiate GALD from other causes of neonatal liver failure. Dr. Taylor’s research is fostering a better understanding of GALD’s disease process to help launch future research and the development of life-saving therapies for newborns facing this potentially deadly...