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...
Principal investigator: Pranab Barman, MD Variations in our genetic makeup determine who we are, from hair and eye color to how we respond to drugs. Today, the growing field of personalized medicine looks to our DNA to tailor treatment so that we receive precise and appropriate care. An emerging offshoot, pharmacogenomics looks specifically at the connections between genetics and drug metabolism. Liver transplant recipients must take immunosuppressive medications for a lifetime to prevent organ rejection. Due to unique genetic profiles, though, one drug often does not fit all. The differences in how these medicines are absorbed by individual recipient’s intestines and then processed by the liver range from harmful to ineffective. Too high a dosage—potential kidney problems. Too low a dosage—potential rejection of the new organ. Given the shortage of donor livers in this country and the long wait list of recipients, ensuring the success of every liver transplant is critically important. Thanks to a grant from the Digestive Health Foundation, researchers in Northwestern Medicine’s Division of Gastroenterology and Hepatology will evaluate the impact of drug metabolizing genes on patient outcomes after liver transplant. Taking advantage of Northwestern Medicine’s extensive biobank, the investigators will study blood samples previously collected from 50 liver transplant recipients. They hope to better understand the links between genetics and drug metabolism for this specific patient population. Pranab Barman, MD, and his research team are conducting pharmacogenomic studies focusing on seven specific genes associated with drug metabolism. Analyzing genetic variations between patients, the researchers plan to identify how much the recipient intestine and donor liver independently contribute to metabolizing these crucial medications. The ability to...
