Clinical Investigation in Nonalcoholic Fatty Liver Disease and Nonalcoholic Steatohepatitis

Research Overview

Led by Kathleen Corey, MD, MPH, research in the lab for Clinical Investigations in Nonalcoholic Fatty Liver Disease (NAFLD) and Nonalcoholic Steatohepatitis (NASH) at Massachusetts General Hospital focuses on lipid metabolism in patients with steatosis and steatohepatitis (the progressive form of fatty liver disease where the liver becomes inflamed due to fat accumulation).

Finding Biomarkers and Diagnostics for NAFLD and NASH

The increase in the incidence of obesity has played an important role in the increasing prevalence of NAFLD, the most common cause of liver disease in the United States. More than one-third of Americans and 400 million people worldwide have obesity.

Obesity, which results from the establishment and defense of an elevated fat mass in the body, is associated with more than 65 demonstrated comorbidities, or additional disorders, including diabetes mellitus, cardiovascular disease and several forms of cancer.

Obesity affects multiple metabolic functions of the liver. It is associated with the development of NAFLD-associated steatosis (the abnormal retention of lipids such as fat in the cell) and inflammation, and promotes the progression of several other liver diseases, including hepatitis C and alcoholic liver disease.

Our research is also focused on the development of non-invasive biomarkers for NAFLD. Our goal is to identify clinical and biological indicators that will allow us to diagnose and monitor fatty liver disease without the need for invasive procedures such as liver biopsy. Our group has identified several novel biomarkers of nonalcoholic steatohepatitis (NASH), including non-high-density lipoprotein cholesterol, and is currently evaluating several other promising markers.

Obstructive Sleep Apnea

We are also studying the interaction between obstructive sleep apnea (OSA)—the partial blockage of the upper airway during sleep—and fatty liver disease.

Like fatty liver disease, OSA impacts millions of Americans and carries serious health consequences. Evidence suggests that the chronic intermittent hypoxia (deprivation of oxygen) caused by OSA results in lipid peroxidation (the unnatural breakdown of lipids in the liver), as well as steatosis and steatohepatitis.

Our work has demonstrated that lipid peroxidation, reflected by oxidized phospholipids (OxPL), is increased in patients with NASH and decreases with NASH regression. Thus, lipid peroxidation appears to mechanistically link OSA and NAFLD. However, this link has yet to be evaluated in humans.

In addition, our work has identified the absence of OSA as a strong predictor of normal liver histology in obese patients who would otherwise be at high risk for NAFLD. This suggests that obesity alone may not be sufficient for the development of NAFLD but requires a second risk factor such as OSA.

Our group is currently working to evaluate lipid peroxidation in individuals with OSA and NAFLD and determine if OSA treatment can help NAFLD.

Our lab also conducts numerous clinical trials, including studies for hepatitis B and C treatment, and post-transplant prevention of hepatitis C infection (HCV) in patients undergoing transplant for HCV infection.

Research Projects

• Evaluation of the prevalence and influence of obstructive sleep apnea on non-alcoholic fatty liver disease (NAFLD)
• Understanding lipid oxidation and metabolism in NAFLD
• The impact of weight loss surgery on NAFLD in adolescents
• Cardiovascular risk and NAFLD

Research Positions

No full-time research positions are currently available. Dr. Corey welcomes contact from trainees and researchers interested in clinical or outcomes research in non-alcoholic fatty liver disease.

Publications

Corey KE, Long M, Chung RT. Non-HDL Cholesterol is Predictive of Non-Alcoholic Steatohepatitis. Clinical Gastroenterology and Hepatology 2012

Sinha M, Stanley TL, Webb J, Scirica C, Corey K, Pratt J, et al. Metabolic Effects of Roux-en-Y Gastric Bypass in Obese Adolescents and Young Adults. J Pediatr Gastroenterol Nutr 2012.

Canavan C, Eisenburg J, Meng L, Corey K, Hur C. Ultrasound Elastography for Fibrosis Surveillance Is Cost Effective in Patients with Chronic Hepatitis C Virus in the UK. Dig Dis Sci 2013;58(9):2691-704

Corey KE, Misdraji J, Zheng H, et al. The Absence of Obstructive Sleep Apnea May Protect against Non-Alcoholic Fatty Liver in Patients Undergoing Bariatric Surgery. PLoS One;8(5):e62504.

Corey KE, Stanley MD TL, Misdraji JM et al., Non-Alcoholic Fatty Liver Disease is Highly Prevalent and Underdiagnosed in Obese Adolescents. Pediatric Obesity 2014

Corey KE, Chalasani N. Management of Dyslipidemia as a Cardiovascular Risk Factor in Individuals with Nonalcoholic Fatty Liver Disease. Clin Gastroenterol Hepatol 2014

Corey KE, Kaplan LM. Obesity and Liver Disease. The Epidemic of the 21st Century. Clinical Liver Disease February 2014

Samir A, Corey KE et al. Shear Wave Sonoelastography for the Estimation of Liver Fibrosis in Chronic Liver Disease: Determining Accuracy and Ideal Site for Measurement. In press Radiology 2014.

Corey KE, Misdraji J, Gelrud L, Zheng H, Chung RT, Krauss R.Nonalcoholic Steatohepatitis is Associated with an Atherogenic Lipoprotein Subfraction Profile. Lipids in Health and Disease 2014, 13:100 DOI: 10.1186/1476-511X-13-100

Wright AP and Corey, KE. Statin Therapy in Patients With Cirrhosis. Accepted for publication Frontline Gastroenterology. 2014