Declaration of personal interests: The authors wish to acknowledge the contributions of our co-investigators, study coordinators and staff at each of the participating institutions as follows: University of Colorado School of Medicine, Denver, CO: (Contract N01-DK-9-2327, Grant M01RR-00051) Marcelo Kugelmas, MD, Carol McKinley, RN, Brenda Easley, RN, Shannon Lauriski, BS, Stephanie Shea, BA, Michelle Jaramillo. University of California – Irvine, Irvine, CA: (Contract N01-DK-9-2320, Grant M01RR-00827) Muhammad Sheikh, MD, Norah Milne, MD, Choon Park, RN, William Rietkerk, Richard Kesler-West, M. Mazen Jamal, MD, MPH; Virginia Commonwealth University Health System, Richmond, VA: (Contract N01-DK-9-2322, Grant M01RR-00065) Charlotte Hofmann, RN, Paula Smith, RN; New England Research Institutes, Watertown, MA: (Contract N01-DK-9-2328) Michael C. Doherty, MA, Kristin K Snow, ScD, Marina Mihova, MHA; National Institute of Diabetes and Digestive and Kidney Diseases, Division of Digestive Diseases and Nutrition, Bethesda, MD: James E. Everhart, MD, Jay H. Hoofnagle, MD, Leonard Seeff, MD. Data and Safety Monitoring Board Members: (Chair) Gary L. Davis, MD, Guadalupe Garcia-Tsao, MD, Michael Kutner, PhD, Stanley M. Lemon, MD, Robert P. Perillo, MD. Declaration of funding interests: This study was supported by the National Institute of Diabetes & Digestive & Kidney Diseases (contract numbers are listed below). Additional support was provided by the National Institute of Allergy and Infectious Diseases, the National Cancer Institute, the National Center for Minority Health and Health Disparities and by General Clinical Research Center grants from the National Center for Research Resources, National Institutes of Health (grant numbers are listed below). Additional funding to conduct this study was supplied by Metabolic Solutions, Inc. and by Hoffmann-La Roche, Inc., through a Cooperative Research and Development Agreement with the National Institutes of Health. Financial relationships of the authors with Hoffmann-La Roche, Inc., are as follows: G. T. Everson, M. L. Shiffman, T. R. Morgan and R. K. Sterling are consultants, on the speaker’s bureau and receive research support. J. C. Hoefs is on the speaker’s bureau. Financial relationships of the authors with Metabolic Solutions are: G. T. Everson, M. L. Shiffman, R. K. Sterling and T. R. Morgan received research support and D. A. Wagner is employed, has equity and has intellectual property rights. G. T. Everson and UCHSC have filed US Patent Application No. 60/647,689, ‘Methods for Diagnosis and Intervention of Hepatic Disorders’, 26 January 2005 and International Application Number PCT/US2006/003132 as published under the Patent Cooperation Treaty, World Intellectual Property Organization, International Patent Classification A61K 49/00 (2006.01), International Publication Number WO 2006/081521 A2, 3 August 2006 (03.08.2006). The authors J. L. DeSanto, T. M. Curto and E. C. Wright had no financial relationships to disclose. Contract and grants supporting this study included: University of Colorado School of Medicine, Denver, CO: (Contract N01-DK-9-2327, Grant M01RR-00051), University of California - Irvine, Irvine, CA: (Contract N01-DK-9-2320, Grant M01RR-00827), Virginia Commonwealth University Health System, Richmond, VA: (Contract N01-DK-9-2322, Grant M01RR-00065), and New England Research Institutes, Watertown, MA: (Contract N01-DK-9-2328).