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Alan Hofmann (1931‐2021): A career well spent understanding bile acids

2021; Lippincott Williams & Wilkins; Volume: 75; Issue: 1 Linguagem: Inglês

10.1002/hep.32206

1527-3350

Keith D. Lindor, Paul A. Dawson, Michael Trauner,

Gallbladder and Bile Duct Disorders

Alan Hofmann has been a leader in the field of bile acids for much of his six-decade career. In his master's perspective published in Hepatology in 2009, Alan entitled his journey as: "Bile acids: trying to understand their chemistry and biology with the hope of helping patients." He clearly achieved those ambitious goals, driving forward our understanding of these complex molecules with a highly energetic, engaging, and encouraging manner that touched nearly every member of the bile acid field. Alan was born in Baltimore, Maryland in l931 and attended Johns Hopkins University for college and medical school. After completing his residency and a period as a clinical associate at the National Institutes of Health, Alan's career in bile acids began in earnest while working with Bengt Borgström in Sweden. At the University of Lund, Alan advanced our understanding of how bile acids function in the solubilization and absorption of fat. This was a particularly inspiring period for Alan and his early entry to the published literature included articles on this subject published in Nature and the Journal of Clinical Investigation. After returning from Sweden, Alan worked at the Rockefeller University in New York, the Mayo Clinic, and, since l977, at the University of California San Diego. He subsequently published over 800 articles and provided innumerable lectures around the world. His work focused on bile acid chemistry, the mixed micelle, bile acid metabolism and function, bile acids in the intestine, bile acids in cholestatic liver disease, bile acids in gallstone dissolution, and the therapeutic role of novel bile acid agonists and antagonists. In keeping with the theme of his master's perspective, Alan made important contributions to the development of new approved therapies for liver disease, including the bile acid sequestrant, colesevelam, the steroidal farnesoid x-receptor agonist, obeticholic acid, for treatment of primary biliary cholangitis, and the ileal bile acid transporter inhibitor, odevixibat, for treatment of primary familial intrahepatic cholestasis, and therapies in development such as the bile salt hydrolase-resistant bile acid analog, cholylsarcosine, as a potential bile acid replacement therapy for short bowel, 11C-cholylsarcosine for use in PET imaging, and the side chain shortened bile acid analog, norucholic acid (norursodeoxycholic acid). Alan was a highly visible standard bearer for bile acids in the national and international liver community, including as an organizer for the Kroc Foundation Conference on the Physical Chemistry of Bile and the Biennial Congresses on Bile Acid Research that were held in Cortina d'Amprezzo. In the early 1970s, Alan established a Biennial Bile Acid Meeting with Gustav Paumgartner, which is supported by the Falk Foundation and continues to this day. The Falk International Bile Acid Meetings have become the premiere venue for presentation of new discoveries and discussion of bile-acid–related research from labs around the world. Alan's unbroken record of attendance at the Annual Meeting of the American Association for the Study of Liver Diseases (AASLD) spanned almost 50 years, ending only in 2018 when health concerns began to limit his travel. Alan was past president of the AASLD in l984. He established a fellowship at his alma mater, Johns Hopkins University, and was honored with a named fellowship at the AASLD along with every important award in his field. These include the William Beaumont Prize and Friedenwald Medal, both from the American Gastroenterology Association, Distinguished Achievement Award from the AASLD, Distinguished Alumnus from the Mayo Clinic, and the Herbert Falk Medal, among dozens of other awards. Almost everyone active in the field of bile acids over the past 60 years was influenced by Alan and in a most positive way. A partial alphabetized list of mentees and collaborators includes E.H. Ahrens, Ulrich Beuers, Ulrich Bolder, Paul Dawson, Rudy Dazinger, Hermon Dowling, Peter Fickert, Scott Grundy, Devorah Gurantz, Lee Hagey, Neville Hoffman, Takashi Iida, Dietrich Keppler, Steven Kozmary, Matt Krasowski, Nicholas LaRusso, Jan Lillienau, Keith Lindor, Erwin Mosbach, Tim Northfield, Eamonn O'Máille, Kel Palmer, Rainer Poley, Aldo Roda, Steve Rossi, Solko Schalm, Juergen Schoelmerich, Leslie Schoenfield, Claudio Schteingart, Joseph Steinbach, Johnson Thistle, Huong-Thu Ton-Nu, Nhan Trang, Michael Trauner, Gerard van Berge Henegouwen, and Yong Bum Yoon. He was insightful, encouraging, and contributed as much as any one individual to inspire new generations of bile acid researchers. His tremendous personal engagement was vital to the strength of the bile acid field, and Alan played an important role in fostering a highly collaborative and supportive community of scientists and clinicians. Alan is survived by his wife, Heli, two children, Anthea Phillips and Cecelia McKenzie, two stepdaughters, Caroline and Isabel, and five grandchildren. His kindness, curiosity, and intellect will be dearly missed by all who knew him. Nothing to report.