This application addresses broad Challenge Area (05) Comparative Effectiveness Research and specific Challenge Topic, 05-EB-101* - Comparative Effectiveness of Advanced Imaging Procedures. Advances in cross-sectional imaging have revolutionized the medical care provided to individuals with disabling medical conditions. Chronic liver disease and cirrhosis, however, remains a major public health problem within the U.S. population culminating in over 40,000 deaths and $1 billion in health care expenditures annually. The major process responsible for this burden of disease is progressive hepatic fibrosis, which traditionally has been diagnosed by liver biopsy. However, the strict reliance on liver biopsy for detecting hepatic fibrosis is hampered by inherent problems related to sampling error, increased cost, and reduced patient acceptance. In turn, noninvasive methods for detecting hepatic fibrosis have been developed yet their utility in clinical situations remains inadequately established. In the present application, we propose to examine the comparative effectiveness of novel quantitative elasticity imaging techniques and serum marker fibrosis panels for detecting clinically significant hepatic fibrosis measured by liver biopsy among human subjects with chronic liver disease. Our specific aims are to 1) prospectively identify and compare the diagnostic accuracies of quantitative elasticity imaging techniques (MRE and transient elastography) with direct and indirect serum fibrosis marker panels and 2) to determine the clinical effectiveness of quantitative elasticity imaging techniques, serum marker panels, and liver biopsy among 150 subjects with chronic hepatitis C, nonalcoholic fatty liver disease, and alcoholic liver disease. In this application, we also intend to determine the reproducibility of quantitative elasticity imaging in a subgroup of individual subjects, and to identify the optimal diagnostic threshold values for detecting stages F2-F4 hepatic fibrosis by elasticity imaging. The impact of noninvasive testing methods and liver biopsy on clinical decision making and patient-related outcomes will include assessments of procedure-related adverse events, false-positive and false-negative test rates compared to liver biopsy, the potential number of liver biopsies saved with noninvasive testing, cost shifting based on utilization of diagnostic test modalities, and patient preference for individual diagnostic tests. Furthermore, the current study design will allow us to also directly identify and evaluate health-related outcomes and resource utilization beyond the grant period. The resources generated for this project will also facilitate future, highly cost-efficient analyses as new data emerge to support novel aspects of comparative effectiveness. The proposed work is Innovative because it extends groundbreaking, NIH-funded work that seeks to shift current paradigms in the diagnosis of hepatic fibrosis utilizing novel methodologies. The Significance of the proposed research is that it addresses an important problem in the field, and the scientific knowledge gained from this research should yield novel, informative data on the comparative effectiveness of diagnostic testing methods for hepatic fibrosis. In turn, the Potential Impact on health is considered to be broad, as these approaches could accelerate the development and testing of innovative pharmacologic therapies for hepatic fibrosis which affects a growing number of persons in this country. In addition to completing the proposed research, the Economic Impact from this award will result in the ability to hire and retain qualified study personnel for completing the project within a 2 year time frame. The funding will ensure continued employment for established individuals and provide new job opportunities for talented individuals with an inclination toward science. Finally, the proposed grant is designed specifically to deliver results within a 2 year period.