A research program will be undertaken by the applicant, Michelle Lai, MD, MPH, in the Division of Gastroenterology at the Beth Israel Deaconess Medical Center (BIDMC). Dr. Lai has had substantial clinical research exposure during her medical school, residency and Gastroenterology fellowship, during which she showed impressive productivity and commitment to an academic career in patient oriented research. Drs. Nezam H. Afdhal and Detlef Schuppan, Associate Professors in the Division of Gastroenterology, BIDMC and Dr. John B. Wong, Professor of Medicine in the Division of Clinical Decision Making, Informatics and Telemedicine at the Tufts Medical Center will serve as mentors. Approximately 30 million Americans are affected with Nonalcoholic fatty liver disease (NAFLD) with spectrum of disease ranging from benign simple steatosis to the more concerning steatohepatitis (NASH). The limitations of the current gold standard of liver biopsy are well established.
The specific aims of the project are: 1 To characterize the extent to which non-invasive tests of liver fibrosis, metabolism, inflammation/apoptosis, and oxidative stress tests can help improve the ability of clinical predictors to differentiate NASH from simple steatosis in patients with NAFLD;2) To develop and validate a mathematical predictive instrument based on components identified above to predict risk of NASH versus simple steatosis;and 3) To examine the cost-effectiveness of alternative diagnostic approaches including liver biopsy, single predictors, and combinations of predictors including the multivariate model from Aim 2 to distinguish NASH versus simple steatosis. In addition to the research component, the applicant will undertake didactic courses at the Harvard School of Public health and the Tufts Sackler Graduate School of Biomedical Sciences. This will include formal training in decision analysis, prediction and predictive modeling, cost-effectiveness and cost-benefit analysis, pharmacoeconomics, data mining, database and genetics and genomics. The very substantial research, educational, and clinical resources of the BIDMC Gastroenterology Division and Liver Center, Harvard School of Public Health, Tufts Sackler School and Division of Clinical Decision Making will be committed to Dr. Lai to ensure successful attainment of the goals of this award.

Public Health Relevance

Limitations of liver biopsy have been well established. This study on noninvasive approaches differentiate simple steatosis from NASH is imperative given the scope of the epidemic. It will give a predictive instrument for NASH as well as answer health policy questions that will have a substantial impact on the national health care budget, clinical practice and on patient health.

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Mentored Patient-Oriented Research Career Development Award (K23)
Project #
Application #
Study Section
Diabetes, Endocrinology and Metabolic Diseases B Subcommittee (DDK)
Program Officer
Podskalny, Judith M,
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Beth Israel Deaconess Medical Center
United States
Zip Code
White, Phillip J; McGarrah, Robert W; Grimsrud, Paul A et al. (2018) The BCKDH Kinase and Phosphatase Integrate BCAA and Lipid Metabolism via Regulation of ATP-Citrate Lyase. Cell Metab 27:1281-1293.e7
Jiang, Z Gordon; Sandhu, Bynvant; Feldbr├╝gge, Linda et al. (2018) Serum Activity of Macrophage-Derived Adenosine Deaminase 2 Is Associated With Liver Fibrosis in Nonalcoholic Fatty Liver Disease. Clin Gastroenterol Hepatol 16:1170-1172
Jiang, Zhenghui G; Tapper, Elliot B; Kim, Misung et al. (2018) Genetic Determinants of Circulating Lipoproteins in Nonalcoholic Fatty Liver Disease. J Clin Gastroenterol 52:444-451
Tapper, Elliot B; Lai, Michelle (2016) Weight loss results in significant improvements in quality of life for patients with nonalcoholic fatty liver disease: A prospective cohort study. Hepatology 63:1184-9
Kim, Mi-Sung; Krawczyk, Sarah A; Doridot, Ludivine et al. (2016) ChREBP regulates fructose-induced glucose production independently of insulin signaling. J Clin Invest 126:4372-4386
Pimentel, Carolina F M G; Jiang, Zhenghui G; Otsubo, Takeshi et al. (2016) Poor Inter-test Reliability Between CK18 Kits as a Biomarker of NASH. Dig Dis Sci 61:905-12
Jiang, Zhenghui G; Tapper, Elliot B; Connelly, Margery A et al. (2016) Steatohepatitis and liver fibrosis are predicted by the characteristics of very low density lipoprotein in nonalcoholic fatty liver disease. Liver Int 36:1213-20
Tapper, Elliot B; Challies, Tracy; Nasser, Imad et al. (2016) The Performance of Vibration Controlled Transient Elastography in a US Cohort of Patients With Nonalcoholic Fatty Liver Disease. Am J Gastroenterol 111:677-84
Corey, Kathleen E; Lai, Michelle; Gelrud, Louis G et al. (2012) Non-high-density lipoprotein cholesterol as a biomarker for nonalcoholic steatohepatitis. Clin Gastroenterol Hepatol 10:651-6