The broad long-term objective of this study is to improve the management of patients with non-alcoholic fatty liver disease (NAFLD) by developing a non-invasive alternative to liver biopsy for the evaluation and monitoring of hepatic steatosis, necroinflammatory change, and fibrosis leading to cirrohsis using novel MR imaging (MRI) and MR spectroscopic (MRS) markers. NAFLD is increasingly recognized as an important clinical problem in both adults and children, fueled by the burgeoning obesity epidemic. Non-alcoholic steatohepatititis (NASH) is characterized by the presence of necroinflammatory changes in addition to simple steatois and carries an increased risk of progression to cirrhosis. The distinction of NASH from simple steatois is therefore of great interest, particularly given the emergence of potential therapies, but currently requires biopsy for both recognition and monitoring. The central hypothesis of this study is that analysis of non-invasive MRI markers of steatosis, inflammation and fibrosis will provide equivalent and/or additional diagnostic information to liver biopsy in patients with NAFLD.
The specific aims are: 1) determine if apparent diffusion coefficient (ADC) values derived from diffusion MR imaging and MR spectroscopic (MRS) markers (lipids, water, and choline containing compounds) correlate with the grade of necroinflammatory change in NASH;2) determine if ADC values and MRS markers correlate with the stage of fibrosis in NASH;3) determine if MRI (relative signal loss of liver on out-of-phase versus in-phase T1-weighted and with and without fat-suppression T2-weighted sequences) and MRS markers correlate with detection of steatosis in NAFLD;4) determine if MRI visceral fat area measurements correlate with histopathologic parameters of disease severity. A multidisciplinary prospective cohort study involving MR studies will be performed on 50 control subjects (healthy liver donors) and 150 consecutive eligible patients with NAFLD. All subjects will have liver biopsy as part of their clinical evaluation within 1 month of imaging. The patients will undergo an MRI examination including diffusion imaging, and MRS. Histopathologic variables will be correlated with MRI and MRS variables. The relevance of this research to public health is the improved management of NAFLD, which affects over two-thirds of the 60 million obese adults in the United States and is also increasing among children. Determination of MRI and MRS markers of hepatic complications of NAFLD would enable the non-invasive diagnosis, and monitoring of both disease progression and response to emerging therapeutic interventions.

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Research Project (R01)
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Medical Imaging Study Section (MEDI)
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Doo, Edward
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University of California San Francisco
Schools of Medicine
San Francisco
United States
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