A Phase 3 Trial of Seladelpar in Primary Biliary Cholangitis.

Autor:	Hirschfield GM; From the Toronto Centre for Liver Disease, Division of Gastroenterology and Hepatology, University Health Network, Toronto General Hospital, Toronto (G.M.H.); the Division of Gastroenterology and Hepatology, University of California Davis School of Medicine, Sacramento (C.L.B.), and CymaBay Therapeutics, Newark (K.Y., Y.-J.C., D.B.C., C.A.M.) - both in California; the University of Texas Southwestern Medical School, Dallas (M.J.M.), and the Departments of Medicine and Surgery, Baylor College of Medicine, Houston (J.M.V.) - both in Texas; the Department of Gastroenterology and Hepatology, University Hospital Zurich, University of Zurich, Zurich, Switzerland (A.E.K.); Liver Institute Northwest, Seattle (K.V.K.); the Division of Digestive Health and Liver Diseases, University of Miami, Miami (C.L.); the Liver Autoimmunity Unit, Hospital Italiano de Buenos Aires, Buenos Aires (A.V.); Centro de Investigación y Gastroenterología, Mexico City (A.L.L.G.C.); the Department of Basic Medical Sciences, Faculty of Public Health in Bytom, Medical University of Silesia, Bytom, Poland (E.J.); the Gastroenterology Institute, Tel Aviv Sourasky Medical Center, Israel and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel (E.Z.); the Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University, College of Medicine, Seongnam, South Korea (S.-H.J.); the Department of Gastroenterology, School of Medicine, Recep Tayyip Erdoğan University, Rize, Turkey (Y.Y.); Barts Liver Centre, Blizard Institute, Queen Mary University of London, London (Y.K.); the Reference Center for Inflammatory Biliary Diseases and Autoimmune Hepatitis, French Network for Rare Liver Disease in Children and Adults FILFOIE, European Reference Network RARE-LIVER, Saint-Antoine Hospital and Research Center, Assistance Publique-Hôpitaux de Paris, Sorbonne University, Paris (C.C.); Liver Centre Hamburg at Ifi-Institute, Hamburg, Germany (P.B.); the Division of Gastroenterology, Center for Autoimmune Liver Diseases, Department of Medicine and Surgery, University of Milan-Bicocca, and the European Reference Network on Hepatological Diseases (ERN RARE-LIVER), Fondazione IRCCS San Gerardo dei Tintori - both in Monza, Italy (P.I.); the Liver Unit, Hospital Clínic Barcelona, Fundació de Recerca Clínic Barcelona-Institut d'Investigacions Biomèdiques August Pi i Sunyer, CIBEREHD, European Reference Network on Hepatological Diseases (ERN-LIVER), University of Barcelona, Barcelona (M.C.L.H.); and Saberg Clinical Research, the Hague, the Netherlands (S.B.). Dr. Hirschfield is the Lily and Terry Horner Chair in Autoimmune Liver Disease Research at Toronto General Hospital., Bowlus CL; From the Toronto Centre for Liver Disease, Division of Gastroenterology and Hepatology, University Health Network, Toronto General Hospital, Toronto (G.M.H.); the Division of Gastroenterology and Hepatology, University of California Davis School of Medicine, Sacramento (C.L.B.), and CymaBay Therapeutics, Newark (K.Y., Y.-J.C., D.B.C., C.A.M.) - both in California; the University of Texas Southwestern Medical School, Dallas (M.J.M.), and the Departments of Medicine and Surgery, Baylor College of Medicine, Houston (J.M.V.) - both in Texas; the Department of Gastroenterology and Hepatology, University Hospital Zurich, University of Zurich, Zurich, Switzerland (A.E.K.); Liver Institute Northwest, Seattle (K.V.K.); the Division of Digestive Health and Liver Diseases, University of Miami, Miami (C.L.); the Liver Autoimmunity Unit, Hospital Italiano de Buenos Aires, Buenos Aires (A.V.); Centro de Investigación y Gastroenterología, Mexico City (A.L.L.G.C.); the Department of Basic Medical Sciences, Faculty of Public Health in Bytom, Medical University of Silesia, Bytom, Poland (E.J.); the Gastroenterology Institute, Tel Aviv Sourasky Medical Center, Israel and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel (E.Z.); the Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University, College of Medicine, Seongnam, South Korea (S.-H.J.); the Department of Gastroenterology, School of Medicine, Recep Tayyip Erdoğan University, Rize, Turkey (Y.Y.); Barts Liver Centre, Blizard Institute, Queen Mary University of London, London (Y.K.); the Reference Center for Inflammatory Biliary Diseases and Autoimmune Hepatitis, French Network for Rare Liver Disease in Children and Adults FILFOIE, European Reference Network RARE-LIVER, Saint-Antoine Hospital and Research Center, Assistance Publique-Hôpitaux de Paris, Sorbonne University, Paris (C.C.); Liver Centre Hamburg at Ifi-Institute, Hamburg, Germany (P.B.); the Division of Gastroenterology, Center for Autoimmune Liver Diseases, Department of Medicine and Surgery, University of Milan-Bicocca, and the European Reference Network on Hepatological Diseases (ERN RARE-LIVER), Fondazione IRCCS San Gerardo dei Tintori - both in Monza, Italy (P.I.); the Liver Unit, Hospital Clínic Barcelona, Fundació de Recerca Clínic Barcelona-Institut d'Investigacions Biomèdiques August Pi i Sunyer, CIBEREHD, European Reference Network on Hepatological Diseases (ERN-LIVER), University of Barcelona, Barcelona (M.C.L.H.); and Saberg Clinical Research, the Hague, the Netherlands (S.B.). Dr. Hirschfield is the Lily and Terry Horner Chair in Autoimmune Liver Disease Research at Toronto General Hospital., Mayo MJ; From the Toronto Centre for Liver Disease, Division of Gastroenterology and Hepatology, University Health Network, Toronto General Hospital, Toronto (G.M.H.); the Division of Gastroenterology and Hepatology, University of California Davis School of Medicine, Sacramento (C.L.B.), and CymaBay Therapeutics, Newark (K.Y., Y.-J.C., D.B.C., C.A.M.) - both in California; the University of Texas Southwestern Medical School, Dallas (M.J.M.), and the Departments of Medicine and Surgery, Baylor College of Medicine, Houston (J.M.V.) - both in Texas; the Department of Gastroenterology and Hepatology, University Hospital Zurich, University of Zurich, Zurich, Switzerland (A.E.K.); Liver Institute Northwest, Seattle (K.V.K.); the Division of Digestive Health and Liver Diseases, University of Miami, Miami (C.L.); the Liver Autoimmunity Unit, Hospital Italiano de Buenos Aires, Buenos Aires (A.V.); Centro de Investigación y Gastroenterología, Mexico City (A.L.L.G.C.); the Department of Basic Medical Sciences, Faculty of Public Health in Bytom, Medical University of Silesia, Bytom, Poland (E.J.); the Gastroenterology Institute, Tel Aviv Sourasky Medical Center, Israel and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel (E.Z.); the Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University, College of Medicine, Seongnam, South Korea (S.-H.J.); the Department of Gastroenterology, School of Medicine, Recep Tayyip Erdoğan University, Rize, Turkey (Y.Y.); Barts Liver Centre, Blizard Institute, Queen Mary University of London, London (Y.K.); the Reference Center for Inflammatory Biliary Diseases and Autoimmune Hepatitis, French Network for Rare Liver Disease in Children and Adults FILFOIE, European Reference Network RARE-LIVER, Saint-Antoine Hospital and Research Center, Assistance Publique-Hôpitaux de Paris, Sorbonne University, Paris (C.C.); Liver Centre Hamburg at Ifi-Institute, Hamburg, Germany (P.B.); the Division of Gastroenterology, Center for Autoimmune Liver Diseases, Department of Medicine and Surgery, University of Milan-Bicocca, and the European Reference Network on Hepatological Diseases (ERN RARE-LIVER), Fondazione IRCCS San Gerardo dei Tintori - both in Monza, Italy (P.I.); the Liver Unit, Hospital Clínic Barcelona, Fundació de Recerca Clínic Barcelona-Institut d'Investigacions Biomèdiques August Pi i Sunyer, CIBEREHD, European Reference Network on Hepatological Diseases (ERN-LIVER), University of Barcelona, Barcelona (M.C.L.H.); and Saberg Clinical Research, the Hague, the Netherlands (S.B.). Dr. Hirschfield is the Lily and Terry Horner Chair in Autoimmune Liver Disease Research at Toronto General Hospital., Kremer AE; From the Toronto Centre for Liver Disease, Division of Gastroenterology and Hepatology, University Health Network, Toronto General Hospital, Toronto (G.M.H.); the Division of Gastroenterology and Hepatology, University of California Davis School of Medicine, Sacramento (C.L.B.), and CymaBay Therapeutics, Newark (K.Y., Y.-J.C., D.B.C., C.A.M.) - both in California; the University of Texas Southwestern Medical School, Dallas (M.J.M.), and the Departments of Medicine and Surgery, Baylor College of Medicine, Houston (J.M.V.) - both in Texas; the Department of Gastroenterology and Hepatology, University Hospital Zurich, University of Zurich, Zurich, Switzerland (A.E.K.); Liver Institute Northwest, Seattle (K.V.K.); the Division of Digestive Health and Liver Diseases, University of Miami, Miami (C.L.); the Liver Autoimmunity Unit, Hospital Italiano de Buenos Aires, Buenos Aires (A.V.); Centro de Investigación y Gastroenterología, Mexico City (A.L.L.G.C.); the Department of Basic Medical Sciences, Faculty of Public Health in Bytom, Medical University of Silesia, Bytom, Poland (E.J.); the Gastroenterology Institute, Tel Aviv Sourasky Medical Center, Israel and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel (E.Z.); the Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University, College of Medicine, Seongnam, South Korea (S.-H.J.); the Department of Gastroenterology, School of Medicine, Recep Tayyip Erdoğan University, Rize, Turkey (Y.Y.); Barts Liver Centre, Blizard Institute, Queen Mary University of London, London (Y.K.); the Reference Center for Inflammatory Biliary Diseases and Autoimmune Hepatitis, French Network for Rare Liver Disease in Children and Adults FILFOIE, European Reference Network RARE-LIVER, Saint-Antoine Hospital and Research Center, Assistance Publique-Hôpitaux de Paris, Sorbonne University, Paris (C.C.); Liver Centre Hamburg at Ifi-Institute, Hamburg, Germany (P.B.); the Division of Gastroenterology, Center for Autoimmune Liver Diseases, Department of Medicine and Surgery, University of Milan-Bicocca, and the European Reference Network on Hepatological Diseases (ERN RARE-LIVER), Fondazione IRCCS San Gerardo dei Tintori - both in Monza, Italy (P.I.); the Liver Unit, Hospital Clínic Barcelona, Fundació de Recerca Clínic Barcelona-Institut d'Investigacions Biomèdiques August Pi i Sunyer, CIBEREHD, European Reference Network on Hepatological Diseases (ERN-LIVER), University of Barcelona, Barcelona (M.C.L.H.); and Saberg Clinical Research, the Hague, the Netherlands (S.B.). Dr. Hirschfield is the Lily and Terry Horner Chair in Autoimmune Liver Disease Research at Toronto General Hospital., Vierling JM; From the Toronto Centre for Liver Disease, Division of Gastroenterology and Hepatology, University Health Network, Toronto General Hospital, Toronto (G.M.H.); the Division of Gastroenterology and Hepatology, University of California Davis School of Medicine, Sacramento (C.L.B.), and CymaBay Therapeutics, Newark (K.Y., Y.-J.C., D.B.C., C.A.M.) - both in California; the University of Texas Southwestern Medical School, Dallas (M.J.M.), and the Departments of Medicine and Surgery, Baylor College of Medicine, Houston (J.M.V.) - both in Texas; the Department of Gastroenterology and Hepatology, University Hospital Zurich, University of Zurich, Zurich, Switzerland (A.E.K.); Liver Institute Northwest, Seattle (K.V.K.); the Division of Digestive Health and Liver Diseases, University of Miami, Miami (C.L.); the Liver Autoimmunity Unit, Hospital Italiano de Buenos Aires, Buenos Aires (A.V.); Centro de Investigación y Gastroenterología, Mexico City (A.L.L.G.C.); the Department of Basic Medical Sciences, Faculty of Public Health in Bytom, Medical University of Silesia, Bytom, Poland (E.J.); the Gastroenterology Institute, Tel Aviv Sourasky Medical Center, Israel and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel (E.Z.); the Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University, College of Medicine, Seongnam, South Korea (S.-H.J.); the Department of Gastroenterology, School of Medicine, Recep Tayyip Erdoğan University, Rize, Turkey (Y.Y.); Barts Liver Centre, Blizard Institute, Queen Mary University of London, London (Y.K.); the Reference Center for Inflammatory Biliary Diseases and Autoimmune Hepatitis, French Network for Rare Liver Disease in Children and Adults FILFOIE, European Reference Network RARE-LIVER, Saint-Antoine Hospital and Research Center, Assistance Publique-Hôpitaux de Paris, Sorbonne University, Paris (C.C.); Liver Centre Hamburg at Ifi-Institute, Hamburg, Germany (P.B.); the Division of Gastroenterology, Center for Autoimmune Liver Diseases, Department of Medicine and Surgery, University of Milan-Bicocca, and the European Reference Network on Hepatological Diseases (ERN RARE-LIVER), Fondazione IRCCS San Gerardo dei Tintori - both in Monza, Italy (P.I.); the Liver Unit, Hospital Clínic Barcelona, Fundació de Recerca Clínic Barcelona-Institut d'Investigacions Biomèdiques August Pi i Sunyer, CIBEREHD, European Reference Network on Hepatological Diseases (ERN-LIVER), University of Barcelona, Barcelona (M.C.L.H.); and Saberg Clinical Research, the Hague, the Netherlands (S.B.). Dr. Hirschfield is the Lily and Terry Horner Chair in Autoimmune Liver Disease Research at Toronto General Hospital., Kowdley KV; From the Toronto Centre for Liver Disease, Division of Gastroenterology and Hepatology, University Health Network, Toronto General Hospital, Toronto (G.M.H.); the Division of Gastroenterology and Hepatology, University of California Davis School of Medicine, Sacramento (C.L.B.), and CymaBay Therapeutics, Newark (K.Y., Y.-J.C., D.B.C., C.A.M.) - both in California; the University of Texas Southwestern Medical School, Dallas (M.J.M.), and the Departments of Medicine and Surgery, Baylor College of Medicine, Houston (J.M.V.) - both in Texas; the Department of Gastroenterology and Hepatology, University Hospital Zurich, University of Zurich, Zurich, Switzerland (A.E.K.); Liver Institute Northwest, Seattle (K.V.K.); the Division of Digestive Health and Liver Diseases, University of Miami, Miami (C.L.); the Liver Autoimmunity Unit, Hospital Italiano de Buenos Aires, Buenos Aires (A.V.); Centro de Investigación y Gastroenterología, Mexico City (A.L.L.G.C.); the Department of Basic Medical Sciences, Faculty of Public Health in Bytom, Medical University of Silesia, Bytom, Poland (E.J.); the Gastroenterology Institute, Tel Aviv Sourasky Medical Center, Israel and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel (E.Z.); the Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University, College of Medicine, Seongnam, South Korea (S.-H.J.); the Department of Gastroenterology, School of Medicine, Recep Tayyip Erdoğan University, Rize, Turkey (Y.Y.); Barts Liver Centre, Blizard Institute, Queen Mary University of London, London (Y.K.); the Reference Center for Inflammatory Biliary Diseases and Autoimmune Hepatitis, French Network for Rare Liver Disease in Children and Adults FILFOIE, European Reference Network RARE-LIVER, Saint-Antoine Hospital and Research Center, Assistance Publique-Hôpitaux de Paris, Sorbonne University, Paris (C.C.); Liver Centre Hamburg at Ifi-Institute, Hamburg, Germany (P.B.); the Division of Gastroenterology, Center for Autoimmune Liver Diseases, Department of Medicine and Surgery, University of Milan-Bicocca, and the European Reference Network on Hepatological Diseases (ERN RARE-LIVER), Fondazione IRCCS San Gerardo dei Tintori - both in Monza, Italy (P.I.); the Liver Unit, Hospital Clínic Barcelona, Fundació de Recerca Clínic Barcelona-Institut d'Investigacions Biomèdiques August Pi i Sunyer, CIBEREHD, European Reference Network on Hepatological Diseases (ERN-LIVER), University of Barcelona, Barcelona (M.C.L.H.); and Saberg Clinical Research, the Hague, the Netherlands (S.B.). Dr. Hirschfield is the Lily and Terry Horner Chair in Autoimmune Liver Disease Research at Toronto General Hospital., Levy C; From the Toronto Centre for Liver Disease, Division of Gastroenterology and Hepatology, University Health Network, Toronto General Hospital, Toronto (G.M.H.); the Division of Gastroenterology and Hepatology, University of California Davis School of Medicine, Sacramento (C.L.B.), and CymaBay Therapeutics, Newark (K.Y., Y.-J.C., D.B.C., C.A.M.) - both in California; the University of Texas Southwestern Medical School, Dallas (M.J.M.), and the Departments of Medicine and Surgery, Baylor College of Medicine, Houston (J.M.V.) - both in Texas; the Department of Gastroenterology and Hepatology, University Hospital Zurich, University of Zurich, Zurich, Switzerland (A.E.K.); Liver Institute Northwest, Seattle (K.V.K.); the Division of Digestive Health and Liver Diseases, University of Miami, Miami (C.L.); the Liver Autoimmunity Unit, Hospital Italiano de Buenos Aires, Buenos Aires (A.V.); Centro de Investigación y Gastroenterología, Mexico City (A.L.L.G.C.); the Department of Basic Medical Sciences, Faculty of Public Health in Bytom, Medical University of Silesia, Bytom, Poland (E.J.); the Gastroenterology Institute, Tel Aviv Sourasky Medical Center, Israel and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel (E.Z.); the Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University, College of Medicine, Seongnam, South Korea (S.-H.J.); the Department of Gastroenterology, School of Medicine, Recep Tayyip Erdoğan University, Rize, Turkey (Y.Y.); Barts Liver Centre, Blizard Institute, Queen Mary University of London, London (Y.K.); the Reference Center for Inflammatory Biliary Diseases and Autoimmune Hepatitis, French Network for Rare Liver Disease in Children and Adults FILFOIE, European Reference Network RARE-LIVER, Saint-Antoine Hospital and Research Center, Assistance Publique-Hôpitaux de Paris, Sorbonne University, Paris (C.C.); Liver Centre Hamburg at Ifi-Institute, Hamburg, Germany (P.B.); the Division of Gastroenterology, Center for Autoimmune Liver Diseases, Department of Medicine and Surgery, University of Milan-Bicocca, and the European Reference Network on Hepatological Diseases (ERN RARE-LIVER), Fondazione IRCCS San Gerardo dei Tintori - both in Monza, Italy (P.I.); the Liver Unit, Hospital Clínic Barcelona, Fundació de Recerca Clínic Barcelona-Institut d'Investigacions Biomèdiques August Pi i Sunyer, CIBEREHD, European Reference Network on Hepatological Diseases (ERN-LIVER), University of Barcelona, Barcelona (M.C.L.H.); and Saberg Clinical Research, the Hague, the Netherlands (S.B.). Dr. Hirschfield is the Lily and Terry Horner Chair in Autoimmune Liver Disease Research at Toronto General Hospital., Villamil A; From the Toronto Centre for Liver Disease, Division of Gastroenterology and Hepatology, University Health Network, Toronto General Hospital, Toronto (G.M.H.); the Division of Gastroenterology and Hepatology, University of California Davis School of Medicine, Sacramento (C.L.B.), and CymaBay Therapeutics, Newark (K.Y., Y.-J.C., D.B.C., C.A.M.) - both in California; the University of Texas Southwestern Medical School, Dallas (M.J.M.), and the Departments of Medicine and Surgery, Baylor College of Medicine, Houston (J.M.V.) - both in Texas; the Department of Gastroenterology and Hepatology, University Hospital Zurich, University of Zurich, Zurich, Switzerland (A.E.K.); Liver Institute Northwest, Seattle (K.V.K.); the Division of Digestive Health and Liver Diseases, University of Miami, Miami (C.L.); the Liver Autoimmunity Unit, Hospital Italiano de Buenos Aires, Buenos Aires (A.V.); Centro de Investigación y Gastroenterología, Mexico City (A.L.L.G.C.); the Department of Basic Medical Sciences, Faculty of Public Health in Bytom, Medical University of Silesia, Bytom, Poland (E.J.); the Gastroenterology Institute, Tel Aviv Sourasky Medical Center, Israel and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel (E.Z.); the Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University, College of Medicine, Seongnam, South Korea (S.-H.J.); the Department of Gastroenterology, School of Medicine, Recep Tayyip Erdoğan University, Rize, Turkey (Y.Y.); Barts Liver Centre, Blizard Institute, Queen Mary University of London, London (Y.K.); the Reference Center for Inflammatory Biliary Diseases and Autoimmune Hepatitis, French Network for Rare Liver Disease in Children and Adults FILFOIE, European Reference Network RARE-LIVER, Saint-Antoine Hospital and Research Center, Assistance Publique-Hôpitaux de Paris, Sorbonne University, Paris (C.C.); Liver Centre Hamburg at Ifi-Institute, Hamburg, Germany (P.B.); the Division of Gastroenterology, Center for Autoimmune Liver Diseases, Department of Medicine and Surgery, University of Milan-Bicocca, and the European Reference Network on Hepatological Diseases (ERN RARE-LIVER), Fondazione IRCCS San Gerardo dei Tintori - both in Monza, Italy (P.I.); the Liver Unit, Hospital Clínic Barcelona, Fundació de Recerca Clínic Barcelona-Institut d'Investigacions Biomèdiques August Pi i Sunyer, CIBEREHD, European Reference Network on Hepatological Diseases (ERN-LIVER), University of Barcelona, Barcelona (M.C.L.H.); and Saberg Clinical Research, the Hague, the Netherlands (S.B.). Dr. Hirschfield is the Lily and Terry Horner Chair in Autoimmune Liver Disease Research at Toronto General Hospital., Ladrón de Guevara Cetina AL; From the Toronto Centre for Liver Disease, Division of Gastroenterology and Hepatology, University Health Network, Toronto General Hospital, Toronto (G.M.H.); the Division of Gastroenterology and Hepatology, University of California Davis School of Medicine, Sacramento (C.L.B.), and CymaBay Therapeutics, Newark (K.Y., Y.-J.C., D.B.C., C.A.M.) - both in California; the University of Texas Southwestern Medical School, Dallas (M.J.M.), and the Departments of Medicine and Surgery, Baylor College of Medicine, Houston (J.M.V.) - both in Texas; the Department of Gastroenterology and Hepatology, University Hospital Zurich, University of Zurich, Zurich, Switzerland (A.E.K.); Liver Institute Northwest, Seattle (K.V.K.); the Division of Digestive Health and Liver Diseases, University of Miami, Miami (C.L.); the Liver Autoimmunity Unit, Hospital Italiano de Buenos Aires, Buenos Aires (A.V.); Centro de Investigación y Gastroenterología, Mexico City (A.L.L.G.C.); the Department of Basic Medical Sciences, Faculty of Public Health in Bytom, Medical University of Silesia, Bytom, Poland (E.J.); the Gastroenterology Institute, Tel Aviv Sourasky Medical Center, Israel and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel (E.Z.); the Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University, College of Medicine, Seongnam, South Korea (S.-H.J.); the Department of Gastroenterology, School of Medicine, Recep Tayyip Erdoğan University, Rize, Turkey (Y.Y.); Barts Liver Centre, Blizard Institute, Queen Mary University of London, London (Y.K.); the Reference Center for Inflammatory Biliary Diseases and Autoimmune Hepatitis, French Network for Rare Liver Disease in Children and Adults FILFOIE, European Reference Network RARE-LIVER, Saint-Antoine Hospital and Research Center, Assistance Publique-Hôpitaux de Paris, Sorbonne University, Paris (C.C.); Liver Centre Hamburg at Ifi-Institute, Hamburg, Germany (P.B.); the Division of Gastroenterology, Center for Autoimmune Liver Diseases, Department of Medicine and Surgery, University of Milan-Bicocca, and the European Reference Network on Hepatological Diseases (ERN RARE-LIVER), Fondazione IRCCS San Gerardo dei Tintori - both in Monza, Italy (P.I.); the Liver Unit, Hospital Clínic Barcelona, Fundació de Recerca Clínic Barcelona-Institut d'Investigacions Biomèdiques August Pi i Sunyer, CIBEREHD, European Reference Network on Hepatological Diseases (ERN-LIVER), University of Barcelona, Barcelona (M.C.L.H.); and Saberg Clinical Research, the Hague, the Netherlands (S.B.). Dr. Hirschfield is the Lily and Terry Horner Chair in Autoimmune Liver Disease Research at Toronto General Hospital., Janczewska E; From the Toronto Centre for Liver Disease, Division of Gastroenterology and Hepatology, University Health Network, Toronto General Hospital, Toronto (G.M.H.); the Division of Gastroenterology and Hepatology, University of California Davis School of Medicine, Sacramento (C.L.B.), and CymaBay Therapeutics, Newark (K.Y., Y.-J.C., D.B.C., C.A.M.) - both in California; the University of Texas Southwestern Medical School, Dallas (M.J.M.), and the Departments of Medicine and Surgery, Baylor College of Medicine, Houston (J.M.V.) - both in Texas; the Department of Gastroenterology and Hepatology, University Hospital Zurich, University of Zurich, Zurich, Switzerland (A.E.K.); Liver Institute Northwest, Seattle (K.V.K.); the Division of Digestive Health and Liver Diseases, University of Miami, Miami (C.L.); the Liver Autoimmunity Unit, Hospital Italiano de Buenos Aires, Buenos Aires (A.V.); Centro de Investigación y Gastroenterología, Mexico City (A.L.L.G.C.); the Department of Basic Medical Sciences, Faculty of Public Health in Bytom, Medical University of Silesia, Bytom, Poland (E.J.); the Gastroenterology Institute, Tel Aviv Sourasky Medical Center, Israel and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel (E.Z.); the Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University, College of Medicine, Seongnam, South Korea (S.-H.J.); the Department of Gastroenterology, School of Medicine, Recep Tayyip Erdoğan University, Rize, Turkey (Y.Y.); Barts Liver Centre, Blizard Institute, Queen Mary University of London, London (Y.K.); the Reference Center for Inflammatory Biliary Diseases and Autoimmune Hepatitis, French Network for Rare Liver Disease in Children and Adults FILFOIE, European Reference Network RARE-LIVER, Saint-Antoine Hospital and Research Center, Assistance Publique-Hôpitaux de Paris, Sorbonne University, Paris (C.C.); Liver Centre Hamburg at Ifi-Institute, Hamburg, Germany (P.B.); the Division of Gastroenterology, Center for Autoimmune Liver Diseases, Department of Medicine and Surgery, University of Milan-Bicocca, and the European Reference Network on Hepatological Diseases (ERN RARE-LIVER), Fondazione IRCCS San Gerardo dei Tintori - both in Monza, Italy (P.I.); the Liver Unit, Hospital Clínic Barcelona, Fundació de Recerca Clínic Barcelona-Institut d'Investigacions Biomèdiques August Pi i Sunyer, CIBEREHD, European Reference Network on Hepatological Diseases (ERN-LIVER), University of Barcelona, Barcelona (M.C.L.H.); and Saberg Clinical Research, the Hague, the Netherlands (S.B.). Dr. Hirschfield is the Lily and Terry Horner Chair in Autoimmune Liver Disease Research at Toronto General Hospital., Zigmond E; From the Toronto Centre for Liver Disease, Division of Gastroenterology and Hepatology, University Health Network, Toronto General Hospital, Toronto (G.M.H.); the Division of Gastroenterology and Hepatology, University of California Davis School of Medicine, Sacramento (C.L.B.), and CymaBay Therapeutics, Newark (K.Y., Y.-J.C., D.B.C., C.A.M.) - both in California; the University of Texas Southwestern Medical School, Dallas (M.J.M.), and the Departments of Medicine and Surgery, Baylor College of Medicine, Houston (J.M.V.) - both in Texas; the Department of Gastroenterology and Hepatology, University Hospital Zurich, University of Zurich, Zurich, Switzerland (A.E.K.); Liver Institute Northwest, Seattle (K.V.K.); the Division of Digestive Health and Liver Diseases, University of Miami, Miami (C.L.); the Liver Autoimmunity Unit, Hospital Italiano de Buenos Aires, Buenos Aires (A.V.); Centro de Investigación y Gastroenterología, Mexico City (A.L.L.G.C.); the Department of Basic Medical Sciences, Faculty of Public Health in Bytom, Medical University of Silesia, Bytom, Poland (E.J.); the Gastroenterology Institute, Tel Aviv Sourasky Medical Center, Israel and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel (E.Z.); the Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University, College of Medicine, Seongnam, South Korea (S.-H.J.); the Department of Gastroenterology, School of Medicine, Recep Tayyip Erdoğan University, Rize, Turkey (Y.Y.); Barts Liver Centre, Blizard Institute, Queen Mary University of London, London (Y.K.); the Reference Center for Inflammatory Biliary Diseases and Autoimmune Hepatitis, French Network for Rare Liver Disease in Children and Adults FILFOIE, European Reference Network RARE-LIVER, Saint-Antoine Hospital and Research Center, Assistance Publique-Hôpitaux de Paris, Sorbonne University, Paris (C.C.); Liver Centre Hamburg at Ifi-Institute, Hamburg, Germany (P.B.); the Division of Gastroenterology, Center for Autoimmune Liver Diseases, Department of Medicine and Surgery, University of Milan-Bicocca, and the European Reference Network on Hepatological Diseases (ERN RARE-LIVER), Fondazione IRCCS San Gerardo dei Tintori - both in Monza, Italy (P.I.); the Liver Unit, Hospital Clínic Barcelona, Fundació de Recerca Clínic Barcelona-Institut d'Investigacions Biomèdiques August Pi i Sunyer, CIBEREHD, European Reference Network on Hepatological Diseases (ERN-LIVER), University of Barcelona, Barcelona (M.C.L.H.); and Saberg Clinical Research, the Hague, the Netherlands (S.B.). Dr. Hirschfield is the Lily and Terry Horner Chair in Autoimmune Liver Disease Research at Toronto General Hospital., Jeong SH; From the Toronto Centre for Liver Disease, Division of Gastroenterology and Hepatology, University Health Network, Toronto General Hospital, Toronto (G.M.H.); the Division of Gastroenterology and Hepatology, University of California Davis School of Medicine, Sacramento (C.L.B.), and CymaBay Therapeutics, Newark (K.Y., Y.-J.C., D.B.C., C.A.M.) - both in California; the University of Texas Southwestern Medical School, Dallas (M.J.M.), and the Departments of Medicine and Surgery, Baylor College of Medicine, Houston (J.M.V.) - both in Texas; the Department of Gastroenterology and Hepatology, University Hospital Zurich, University of Zurich, Zurich, Switzerland (A.E.K.); Liver Institute Northwest, Seattle (K.V.K.); the Division of Digestive Health and Liver Diseases, University of Miami, Miami (C.L.); the Liver Autoimmunity Unit, Hospital Italiano de Buenos Aires, Buenos Aires (A.V.); Centro de Investigación y Gastroenterología, Mexico City (A.L.L.G.C.); the Department of Basic Medical Sciences, Faculty of Public Health in Bytom, Medical University of Silesia, Bytom, Poland (E.J.); the Gastroenterology Institute, Tel Aviv Sourasky Medical Center, Israel and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel (E.Z.); the Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University, College of Medicine, Seongnam, South Korea (S.-H.J.); the Department of Gastroenterology, School of Medicine, Recep Tayyip Erdoğan University, Rize, Turkey (Y.Y.); Barts Liver Centre, Blizard Institute, Queen Mary University of London, London (Y.K.); the Reference Center for Inflammatory Biliary Diseases and Autoimmune Hepatitis, French Network for Rare Liver Disease in Children and Adults FILFOIE, European Reference Network RARE-LIVER, Saint-Antoine Hospital and Research Center, Assistance Publique-Hôpitaux de Paris, Sorbonne University, Paris (C.C.); Liver Centre Hamburg at Ifi-Institute, Hamburg, Germany (P.B.); the Division of Gastroenterology, Center for Autoimmune Liver Diseases, Department of Medicine and Surgery, University of Milan-Bicocca, and the European Reference Network on Hepatological Diseases (ERN RARE-LIVER), Fondazione IRCCS San Gerardo dei Tintori - both in Monza, Italy (P.I.); the Liver Unit, Hospital Clínic Barcelona, Fundació de Recerca Clínic Barcelona-Institut d'Investigacions Biomèdiques August Pi i Sunyer, CIBEREHD, European Reference Network on Hepatological Diseases (ERN-LIVER), University of Barcelona, Barcelona (M.C.L.H.); and Saberg Clinical Research, the Hague, the Netherlands (S.B.). Dr. Hirschfield is the Lily and Terry Horner Chair in Autoimmune Liver Disease Research at Toronto General Hospital., Yilmaz Y; From the Toronto Centre for Liver Disease, Division of Gastroenterology and Hepatology, University Health Network, Toronto General Hospital, Toronto (G.M.H.); the Division of Gastroenterology and Hepatology, University of California Davis School of Medicine, Sacramento (C.L.B.), and CymaBay Therapeutics, Newark (K.Y., Y.-J.C., D.B.C., C.A.M.) - both in California; the University of Texas Southwestern Medical School, Dallas (M.J.M.), and the Departments of Medicine and Surgery, Baylor College of Medicine, Houston (J.M.V.) - both in Texas; the Department of Gastroenterology and Hepatology, University Hospital Zurich, University of Zurich, Zurich, Switzerland (A.E.K.); Liver Institute Northwest, Seattle (K.V.K.); the Division of Digestive Health and Liver Diseases, University of Miami, Miami (C.L.); the Liver Autoimmunity Unit, Hospital Italiano de Buenos Aires, Buenos Aires (A.V.); Centro de Investigación y Gastroenterología, Mexico City (A.L.L.G.C.); the Department of Basic Medical Sciences, Faculty of Public Health in Bytom, Medical University of Silesia, Bytom, Poland (E.J.); the Gastroenterology Institute, Tel Aviv Sourasky Medical Center, Israel and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel (E.Z.); the Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University, College of Medicine, Seongnam, South Korea (S.-H.J.); the Department of Gastroenterology, School of Medicine, Recep Tayyip Erdoğan University, Rize, Turkey (Y.Y.); Barts Liver Centre, Blizard Institute, Queen Mary University of London, London (Y.K.); the Reference Center for Inflammatory Biliary Diseases and Autoimmune Hepatitis, French Network for Rare Liver Disease in Children and Adults FILFOIE, European Reference Network RARE-LIVER, Saint-Antoine Hospital and Research Center, Assistance Publique-Hôpitaux de Paris, Sorbonne University, Paris (C.C.); Liver Centre Hamburg at Ifi-Institute, Hamburg, Germany (P.B.); the Division of Gastroenterology, Center for Autoimmune Liver Diseases, Department of Medicine and Surgery, University of Milan-Bicocca, and the European Reference Network on Hepatological Diseases (ERN RARE-LIVER), Fondazione IRCCS San Gerardo dei Tintori - both in Monza, Italy (P.I.); the Liver Unit, Hospital Clínic Barcelona, Fundació de Recerca Clínic Barcelona-Institut d'Investigacions Biomèdiques August Pi i Sunyer, CIBEREHD, European Reference Network on Hepatological Diseases (ERN-LIVER), University of Barcelona, Barcelona (M.C.L.H.); and Saberg Clinical Research, the Hague, the Netherlands (S.B.). Dr. Hirschfield is the Lily and Terry Horner Chair in Autoimmune Liver Disease Research at Toronto General Hospital., Kallis Y; From the Toronto Centre for Liver Disease, Division of Gastroenterology and Hepatology, University Health Network, Toronto General Hospital, Toronto (G.M.H.); the Division of Gastroenterology and Hepatology, University of California Davis School of Medicine, Sacramento (C.L.B.), and CymaBay Therapeutics, Newark (K.Y., Y.-J.C., D.B.C., C.A.M.) - both in California; the University of Texas Southwestern Medical School, Dallas (M.J.M.), and the Departments of Medicine and Surgery, Baylor College of Medicine, Houston (J.M.V.) - both in Texas; the Department of Gastroenterology and Hepatology, University Hospital Zurich, University of Zurich, Zurich, Switzerland (A.E.K.); Liver Institute Northwest, Seattle (K.V.K.); the Division of Digestive Health and Liver Diseases, University of Miami, Miami (C.L.); the Liver Autoimmunity Unit, Hospital Italiano de Buenos Aires, Buenos Aires (A.V.); Centro de Investigación y Gastroenterología, Mexico City (A.L.L.G.C.); the Department of Basic Medical Sciences, Faculty of Public Health in Bytom, Medical University of Silesia, Bytom, Poland (E.J.); the Gastroenterology Institute, Tel Aviv Sourasky Medical Center, Israel and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel (E.Z.); the Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University, College of Medicine, Seongnam, South Korea (S.-H.J.); the Department of Gastroenterology, School of Medicine, Recep Tayyip Erdoğan University, Rize, Turkey (Y.Y.); Barts Liver Centre, Blizard Institute, Queen Mary University of London, London (Y.K.); the Reference Center for Inflammatory Biliary Diseases and Autoimmune Hepatitis, French Network for Rare Liver Disease in Children and Adults FILFOIE, European Reference Network RARE-LIVER, Saint-Antoine Hospital and Research Center, Assistance Publique-Hôpitaux de Paris, Sorbonne University, Paris (C.C.); Liver Centre Hamburg at Ifi-Institute, Hamburg, Germany (P.B.); the Division of Gastroenterology, Center for Autoimmune Liver Diseases, Department of Medicine and Surgery, University of Milan-Bicocca, and the European Reference Network on Hepatological Diseases (ERN RARE-LIVER), Fondazione IRCCS San Gerardo dei Tintori - both in Monza, Italy (P.I.); the Liver Unit, Hospital Clínic Barcelona, Fundació de Recerca Clínic Barcelona-Institut d'Investigacions Biomèdiques August Pi i Sunyer, CIBEREHD, European Reference Network on Hepatological Diseases (ERN-LIVER), University of Barcelona, Barcelona (M.C.L.H.); and Saberg Clinical Research, the Hague, the Netherlands (S.B.). Dr. Hirschfield is the Lily and Terry Horner Chair in Autoimmune Liver Disease Research at Toronto General Hospital., Corpechot C; From the Toronto Centre for Liver Disease, Division of Gastroenterology and Hepatology, University Health Network, Toronto General Hospital, Toronto (G.M.H.); the Division of Gastroenterology and Hepatology, University of California Davis School of Medicine, Sacramento (C.L.B.), and CymaBay Therapeutics, Newark (K.Y., Y.-J.C., D.B.C., C.A.M.) - both in California; the University of Texas Southwestern Medical School, Dallas (M.J.M.), and the Departments of Medicine and Surgery, Baylor College of Medicine, Houston (J.M.V.) - both in Texas; the Department of Gastroenterology and Hepatology, University Hospital Zurich, University of Zurich, Zurich, Switzerland (A.E.K.); Liver Institute Northwest, Seattle (K.V.K.); the Division of Digestive Health and Liver Diseases, University of Miami, Miami (C.L.); the Liver Autoimmunity Unit, Hospital Italiano de Buenos Aires, Buenos Aires (A.V.); Centro de Investigación y Gastroenterología, Mexico City (A.L.L.G.C.); the Department of Basic Medical Sciences, Faculty of Public Health in Bytom, Medical University of Silesia, Bytom, Poland (E.J.); the Gastroenterology Institute, Tel Aviv Sourasky Medical Center, Israel and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel (E.Z.); the Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University, College of Medicine, Seongnam, South Korea (S.-H.J.); the Department of Gastroenterology, School of Medicine, Recep Tayyip Erdoğan University, Rize, Turkey (Y.Y.); Barts Liver Centre, Blizard Institute, Queen Mary University of London, London (Y.K.); the Reference Center for Inflammatory Biliary Diseases and Autoimmune Hepatitis, French Network for Rare Liver Disease in Children and Adults FILFOIE, European Reference Network RARE-LIVER, Saint-Antoine Hospital and Research Center, Assistance Publique-Hôpitaux de Paris, Sorbonne University, Paris (C.C.); Liver Centre Hamburg at Ifi-Institute, Hamburg, Germany (P.B.); the Division of Gastroenterology, Center for Autoimmune Liver Diseases, Department of Medicine and Surgery, University of Milan-Bicocca, and the European Reference Network on Hepatological Diseases (ERN RARE-LIVER), Fondazione IRCCS San Gerardo dei Tintori - both in Monza, Italy (P.I.); the Liver Unit, Hospital Clínic Barcelona, Fundació de Recerca Clínic Barcelona-Institut d'Investigacions Biomèdiques August Pi i Sunyer, CIBEREHD, European Reference Network on Hepatological Diseases (ERN-LIVER), University of Barcelona, Barcelona (M.C.L.H.); and Saberg Clinical Research, the Hague, the Netherlands (S.B.). Dr. Hirschfield is the Lily and Terry Horner Chair in Autoimmune Liver Disease Research at Toronto General Hospital., Buggisch P; From the Toronto Centre for Liver Disease, Division of Gastroenterology and Hepatology, University Health Network, Toronto General Hospital, Toronto (G.M.H.); the Division of Gastroenterology and Hepatology, University of California Davis School of Medicine, Sacramento (C.L.B.), and CymaBay Therapeutics, Newark (K.Y., Y.-J.C., D.B.C., C.A.M.) - both in California; the University of Texas Southwestern Medical School, Dallas (M.J.M.), and the Departments of Medicine and Surgery, Baylor College of Medicine, Houston (J.M.V.) - both in Texas; the Department of Gastroenterology and Hepatology, University Hospital Zurich, University of Zurich, Zurich, Switzerland (A.E.K.); Liver Institute Northwest, Seattle (K.V.K.); the Division of Digestive Health and Liver Diseases, University of Miami, Miami (C.L.); the Liver Autoimmunity Unit, Hospital Italiano de Buenos Aires, Buenos Aires (A.V.); Centro de Investigación y Gastroenterología, Mexico City (A.L.L.G.C.); the Department of Basic Medical Sciences, Faculty of Public Health in Bytom, Medical University of Silesia, Bytom, Poland (E.J.); the Gastroenterology Institute, Tel Aviv Sourasky Medical Center, Israel and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel (E.Z.); the Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University, College of Medicine, Seongnam, South Korea (S.-H.J.); the Department of Gastroenterology, School of Medicine, Recep Tayyip Erdoğan University, Rize, Turkey (Y.Y.); Barts Liver Centre, Blizard Institute, Queen Mary University of London, London (Y.K.); the Reference Center for Inflammatory Biliary Diseases and Autoimmune Hepatitis, French Network for Rare Liver Disease in Children and Adults FILFOIE, European Reference Network RARE-LIVER, Saint-Antoine Hospital and Research Center, Assistance Publique-Hôpitaux de Paris, Sorbonne University, Paris (C.C.); Liver Centre Hamburg at Ifi-Institute, Hamburg, Germany (P.B.); the Division of Gastroenterology, Center for Autoimmune Liver Diseases, Department of Medicine and Surgery, University of Milan-Bicocca, and the European Reference Network on Hepatological Diseases (ERN RARE-LIVER), Fondazione IRCCS San Gerardo dei Tintori - both in Monza, Italy (P.I.); the Liver Unit, Hospital Clínic Barcelona, Fundació de Recerca Clínic Barcelona-Institut d'Investigacions Biomèdiques August Pi i Sunyer, CIBEREHD, European Reference Network on Hepatological Diseases (ERN-LIVER), University of Barcelona, Barcelona (M.C.L.H.); and Saberg Clinical Research, the Hague, the Netherlands (S.B.). Dr. Hirschfield is the Lily and Terry Horner Chair in Autoimmune Liver Disease Research at Toronto General Hospital., Invernizzi P; From the Toronto Centre for Liver Disease, Division of Gastroenterology and Hepatology, University Health Network, Toronto General Hospital, Toronto (G.M.H.); the Division of Gastroenterology and Hepatology, University of California Davis School of Medicine, Sacramento (C.L.B.), and CymaBay Therapeutics, Newark (K.Y., Y.-J.C., D.B.C., C.A.M.) - both in California; the University of Texas Southwestern Medical School, Dallas (M.J.M.), and the Departments of Medicine and Surgery, Baylor College of Medicine, Houston (J.M.V.) - both in Texas; the Department of Gastroenterology and Hepatology, University Hospital Zurich, University of Zurich, Zurich, Switzerland (A.E.K.); Liver Institute Northwest, Seattle (K.V.K.); the Division of Digestive Health and Liver Diseases, University of Miami, Miami (C.L.); the Liver Autoimmunity Unit, Hospital Italiano de Buenos Aires, Buenos Aires (A.V.); Centro de Investigación y Gastroenterología, Mexico City (A.L.L.G.C.); the Department of Basic Medical Sciences, Faculty of Public Health in Bytom, Medical University of Silesia, Bytom, Poland (E.J.); the Gastroenterology Institute, Tel Aviv Sourasky Medical Center, Israel and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel (E.Z.); the Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University, College of Medicine, Seongnam, South Korea (S.-H.J.); the Department of Gastroenterology, School of Medicine, Recep Tayyip Erdoğan University, Rize, Turkey (Y.Y.); Barts Liver Centre, Blizard Institute, Queen Mary University of London, London (Y.K.); the Reference Center for Inflammatory Biliary Diseases and Autoimmune Hepatitis, French Network for Rare Liver Disease in Children and Adults FILFOIE, European Reference Network RARE-LIVER, Saint-Antoine Hospital and Research Center, Assistance Publique-Hôpitaux de Paris, Sorbonne University, Paris (C.C.); Liver Centre Hamburg at Ifi-Institute, Hamburg, Germany (P.B.); the Division of Gastroenterology, Center for Autoimmune Liver Diseases, Department of Medicine and Surgery, University of Milan-Bicocca, and the European Reference Network on Hepatological Diseases (ERN RARE-LIVER), Fondazione IRCCS San Gerardo dei Tintori - both in Monza, Italy (P.I.); the Liver Unit, Hospital Clínic Barcelona, Fundació de Recerca Clínic Barcelona-Institut d'Investigacions Biomèdiques August Pi i Sunyer, CIBEREHD, European Reference Network on Hepatological Diseases (ERN-LIVER), University of Barcelona, Barcelona (M.C.L.H.); and Saberg Clinical Research, the Hague, the Netherlands (S.B.). Dr. Hirschfield is the Lily and Terry Horner Chair in Autoimmune Liver Disease Research at Toronto General Hospital., Londoño Hurtado MC; From the Toronto Centre for Liver Disease, Division of Gastroenterology and Hepatology, University Health Network, Toronto General Hospital, Toronto (G.M.H.); the Division of Gastroenterology and Hepatology, University of California Davis School of Medicine, Sacramento (C.L.B.), and CymaBay Therapeutics, Newark (K.Y., Y.-J.C., D.B.C., C.A.M.) - both in California; the University of Texas Southwestern Medical School, Dallas (M.J.M.), and the Departments of Medicine and Surgery, Baylor College of Medicine, Houston (J.M.V.) - both in Texas; the Department of Gastroenterology and Hepatology, University Hospital Zurich, University of Zurich, Zurich, Switzerland (A.E.K.); Liver Institute Northwest, Seattle (K.V.K.); the Division of Digestive Health and Liver Diseases, University of Miami, Miami (C.L.); the Liver Autoimmunity Unit, Hospital Italiano de Buenos Aires, Buenos Aires (A.V.); Centro de Investigación y Gastroenterología, Mexico City (A.L.L.G.C.); the Department of Basic Medical Sciences, Faculty of Public Health in Bytom, Medical University of Silesia, Bytom, Poland (E.J.); the Gastroenterology Institute, Tel Aviv Sourasky Medical Center, Israel and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel (E.Z.); the Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University, College of Medicine, Seongnam, South Korea (S.-H.J.); the Department of Gastroenterology, School of Medicine, Recep Tayyip Erdoğan University, Rize, Turkey (Y.Y.); Barts Liver Centre, Blizard Institute, Queen Mary University of London, London (Y.K.); the Reference Center for Inflammatory Biliary Diseases and Autoimmune Hepatitis, French Network for Rare Liver Disease in Children and Adults FILFOIE, European Reference Network RARE-LIVER, Saint-Antoine Hospital and Research Center, Assistance Publique-Hôpitaux de Paris, Sorbonne University, Paris (C.C.); Liver Centre Hamburg at Ifi-Institute, Hamburg, Germany (P.B.); the Division of Gastroenterology, Center for Autoimmune Liver Diseases, Department of Medicine and Surgery, University of Milan-Bicocca, and the European Reference Network on Hepatological Diseases (ERN RARE-LIVER), Fondazione IRCCS San Gerardo dei Tintori - both in Monza, Italy (P.I.); the Liver Unit, Hospital Clínic Barcelona, Fundació de Recerca Clínic Barcelona-Institut d'Investigacions Biomèdiques August Pi i Sunyer, CIBEREHD, European Reference Network on Hepatological Diseases (ERN-LIVER), University of Barcelona, Barcelona (M.C.L.H.); and Saberg Clinical Research, the Hague, the Netherlands (S.B.). Dr. Hirschfield is the Lily and Terry Horner Chair in Autoimmune Liver Disease Research at Toronto General Hospital., Bergheanu S; From the Toronto Centre for Liver Disease, Division of Gastroenterology and Hepatology, University Health Network, Toronto General Hospital, Toronto (G.M.H.); the Division of Gastroenterology and Hepatology, University of California Davis School of Medicine, Sacramento (C.L.B.), and CymaBay Therapeutics, Newark (K.Y., Y.-J.C., D.B.C., C.A.M.) - both in California; the University of Texas Southwestern Medical School, Dallas (M.J.M.), and the Departments of Medicine and Surgery, Baylor College of Medicine, Houston (J.M.V.) - both in Texas; the Department of Gastroenterology and Hepatology, University Hospital Zurich, University of Zurich, Zurich, Switzerland (A.E.K.); Liver Institute Northwest, Seattle (K.V.K.); the Division of Digestive Health and Liver Diseases, University of Miami, Miami (C.L.); the Liver Autoimmunity Unit, Hospital Italiano de Buenos Aires, Buenos Aires (A.V.); Centro de Investigación y Gastroenterología, Mexico City (A.L.L.G.C.); the Department of Basic Medical Sciences, Faculty of Public Health in Bytom, Medical University of Silesia, Bytom, Poland (E.J.); the Gastroenterology Institute, Tel Aviv Sourasky Medical Center, Israel and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel (E.Z.); the Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University, College of Medicine, Seongnam, South Korea (S.-H.J.); the Department of Gastroenterology, School of Medicine, Recep Tayyip Erdoğan University, Rize, Turkey (Y.Y.); Barts Liver Centre, Blizard Institute, Queen Mary University of London, London (Y.K.); the Reference Center for Inflammatory Biliary Diseases and Autoimmune Hepatitis, French Network for Rare Liver Disease in Children and Adults FILFOIE, European Reference Network RARE-LIVER, Saint-Antoine Hospital and Research Center, Assistance Publique-Hôpitaux de Paris, Sorbonne University, Paris (C.C.); Liver Centre Hamburg at Ifi-Institute, Hamburg, Germany (P.B.); the Division of Gastroenterology, Center for Autoimmune Liver Diseases, Department of Medicine and Surgery, University of Milan-Bicocca, and the European Reference Network on Hepatological Diseases (ERN RARE-LIVER), Fondazione IRCCS San Gerardo dei Tintori - both in Monza, Italy (P.I.); the Liver Unit, Hospital Clínic Barcelona, Fundació de Recerca Clínic Barcelona-Institut d'Investigacions Biomèdiques August Pi i Sunyer, CIBEREHD, European Reference Network on Hepatological Diseases (ERN-LIVER), University of Barcelona, Barcelona (M.C.L.H.); and Saberg Clinical Research, the Hague, the Netherlands (S.B.). Dr. Hirschfield is the Lily and Terry Horner Chair in Autoimmune Liver Disease Research at Toronto General Hospital., Yang K; From the Toronto Centre for Liver Disease, Division of Gastroenterology and Hepatology, University Health Network, Toronto General Hospital, Toronto (G.M.H.); the Division of Gastroenterology and Hepatology, University of California Davis School of Medicine, Sacramento (C.L.B.), and CymaBay Therapeutics, Newark (K.Y., Y.-J.C., D.B.C., C.A.M.) - both in California; the University of Texas Southwestern Medical School, Dallas (M.J.M.), and the Departments of Medicine and Surgery, Baylor College of Medicine, Houston (J.M.V.) - both in Texas; the Department of Gastroenterology and Hepatology, University Hospital Zurich, University of Zurich, Zurich, Switzerland (A.E.K.); Liver Institute Northwest, Seattle (K.V.K.); the Division of Digestive Health and Liver Diseases, University of Miami, Miami (C.L.); the Liver Autoimmunity Unit, Hospital Italiano de Buenos Aires, Buenos Aires (A.V.); Centro de Investigación y Gastroenterología, Mexico City (A.L.L.G.C.); the Department of Basic Medical Sciences, Faculty of Public Health in Bytom, Medical University of Silesia, Bytom, Poland (E.J.); the Gastroenterology Institute, Tel Aviv Sourasky Medical Center, Israel and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel (E.Z.); the Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University, College of Medicine, Seongnam, South Korea (S.-H.J.); the Department of Gastroenterology, School of Medicine, Recep Tayyip Erdoğan University, Rize, Turkey (Y.Y.); Barts Liver Centre, Blizard Institute, Queen Mary University of London, London (Y.K.); the Reference Center for Inflammatory Biliary Diseases and Autoimmune Hepatitis, French Network for Rare Liver Disease in Children and Adults FILFOIE, European Reference Network RARE-LIVER, Saint-Antoine Hospital and Research Center, Assistance Publique-Hôpitaux de Paris, Sorbonne University, Paris (C.C.); Liver Centre Hamburg at Ifi-Institute, Hamburg, Germany (P.B.); the Division of Gastroenterology, Center for Autoimmune Liver Diseases, Department of Medicine and Surgery, University of Milan-Bicocca, and the European Reference Network on Hepatological Diseases (ERN RARE-LIVER), Fondazione IRCCS San Gerardo dei Tintori - both in Monza, Italy (P.I.); the Liver Unit, Hospital Clínic Barcelona, Fundació de Recerca Clínic Barcelona-Institut d'Investigacions Biomèdiques August Pi i Sunyer, CIBEREHD, European Reference Network on Hepatological Diseases (ERN-LIVER), University of Barcelona, Barcelona (M.C.L.H.); and Saberg Clinical Research, the Hague, the Netherlands (S.B.). Dr. Hirschfield is the Lily and Terry Horner Chair in Autoimmune Liver Disease Research at Toronto General Hospital., Choi YJ; From the Toronto Centre for Liver Disease, Division of Gastroenterology and Hepatology, University Health Network, Toronto General Hospital, Toronto (G.M.H.); the Division of Gastroenterology and Hepatology, University of California Davis School of Medicine, Sacramento (C.L.B.), and CymaBay Therapeutics, Newark (K.Y., Y.-J.C., D.B.C., C.A.M.) - both in California; the University of Texas Southwestern Medical School, Dallas (M.J.M.), and the Departments of Medicine and Surgery, Baylor College of Medicine, Houston (J.M.V.) - both in Texas; the Department of Gastroenterology and Hepatology, University Hospital Zurich, University of Zurich, Zurich, Switzerland (A.E.K.); Liver Institute Northwest, Seattle (K.V.K.); the Division of Digestive Health and Liver Diseases, University of Miami, Miami (C.L.); the Liver Autoimmunity Unit, Hospital Italiano de Buenos Aires, Buenos Aires (A.V.); Centro de Investigación y Gastroenterología, Mexico City (A.L.L.G.C.); the Department of Basic Medical Sciences, Faculty of Public Health in Bytom, Medical University of Silesia, Bytom, Poland (E.J.); the Gastroenterology Institute, Tel Aviv Sourasky Medical Center, Israel and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel (E.Z.); the Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University, College of Medicine, Seongnam, South Korea (S.-H.J.); the Department of Gastroenterology, School of Medicine, Recep Tayyip Erdoğan University, Rize, Turkey (Y.Y.); Barts Liver Centre, Blizard Institute, Queen Mary University of London, London (Y.K.); the Reference Center for Inflammatory Biliary Diseases and Autoimmune Hepatitis, French Network for Rare Liver Disease in Children and Adults FILFOIE, European Reference Network RARE-LIVER, Saint-Antoine Hospital and Research Center, Assistance Publique-Hôpitaux de Paris, Sorbonne University, Paris (C.C.); Liver Centre Hamburg at Ifi-Institute, Hamburg, Germany (P.B.); the Division of Gastroenterology, Center for Autoimmune Liver Diseases, Department of Medicine and Surgery, University of Milan-Bicocca, and the European Reference Network on Hepatological Diseases (ERN RARE-LIVER), Fondazione IRCCS San Gerardo dei Tintori - both in Monza, Italy (P.I.); the Liver Unit, Hospital Clínic Barcelona, Fundació de Recerca Clínic Barcelona-Institut d'Investigacions Biomèdiques August Pi i Sunyer, CIBEREHD, European Reference Network on Hepatological Diseases (ERN-LIVER), University of Barcelona, Barcelona (M.C.L.H.); and Saberg Clinical Research, the Hague, the Netherlands (S.B.). Dr. Hirschfield is the Lily and Terry Horner Chair in Autoimmune Liver Disease Research at Toronto General Hospital., Crittenden DB; From the Toronto Centre for Liver Disease, Division of Gastroenterology and Hepatology, University Health Network, Toronto General Hospital, Toronto (G.M.H.); the Division of Gastroenterology and Hepatology, University of California Davis School of Medicine, Sacramento (C.L.B.), and CymaBay Therapeutics, Newark (K.Y., Y.-J.C., D.B.C., C.A.M.) - both in California; the University of Texas Southwestern Medical School, Dallas (M.J.M.), and the Departments of Medicine and Surgery, Baylor College of Medicine, Houston (J.M.V.) - both in Texas; the Department of Gastroenterology and Hepatology, University Hospital Zurich, University of Zurich, Zurich, Switzerland (A.E.K.); Liver Institute Northwest, Seattle (K.V.K.); the Division of Digestive Health and Liver Diseases, University of Miami, Miami (C.L.); the Liver Autoimmunity Unit, Hospital Italiano de Buenos Aires, Buenos Aires (A.V.); Centro de Investigación y Gastroenterología, Mexico City (A.L.L.G.C.); the Department of Basic Medical Sciences, Faculty of Public Health in Bytom, Medical University of Silesia, Bytom, Poland (E.J.); the Gastroenterology Institute, Tel Aviv Sourasky Medical Center, Israel and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel (E.Z.); the Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University, College of Medicine, Seongnam, South Korea (S.-H.J.); the Department of Gastroenterology, School of Medicine, Recep Tayyip Erdoğan University, Rize, Turkey (Y.Y.); Barts Liver Centre, Blizard Institute, Queen Mary University of London, London (Y.K.); the Reference Center for Inflammatory Biliary Diseases and Autoimmune Hepatitis, French Network for Rare Liver Disease in Children and Adults FILFOIE, European Reference Network RARE-LIVER, Saint-Antoine Hospital and Research Center, Assistance Publique-Hôpitaux de Paris, Sorbonne University, Paris (C.C.); Liver Centre Hamburg at Ifi-Institute, Hamburg, Germany (P.B.); the Division of Gastroenterology, Center for Autoimmune Liver Diseases, Department of Medicine and Surgery, University of Milan-Bicocca, and the European Reference Network on Hepatological Diseases (ERN RARE-LIVER), Fondazione IRCCS San Gerardo dei Tintori - both in Monza, Italy (P.I.); the Liver Unit, Hospital Clínic Barcelona, Fundació de Recerca Clínic Barcelona-Institut d'Investigacions Biomèdiques August Pi i Sunyer, CIBEREHD, European Reference Network on Hepatological Diseases (ERN-LIVER), University of Barcelona, Barcelona (M.C.L.H.); and Saberg Clinical Research, the Hague, the Netherlands (S.B.). Dr. Hirschfield is the Lily and Terry Horner Chair in Autoimmune Liver Disease Research at Toronto General Hospital., McWherter CA; From the Toronto Centre for Liver Disease, Division of Gastroenterology and Hepatology, University Health Network, Toronto General Hospital, Toronto (G.M.H.); the Division of Gastroenterology and Hepatology, University of California Davis School of Medicine, Sacramento (C.L.B.), and CymaBay Therapeutics, Newark (K.Y., Y.-J.C., D.B.C., C.A.M.) - both in California; the University of Texas Southwestern Medical School, Dallas (M.J.M.), and the Departments of Medicine and Surgery, Baylor College of Medicine, Houston (J.M.V.) - both in Texas; the Department of Gastroenterology and Hepatology, University Hospital Zurich, University of Zurich, Zurich, Switzerland (A.E.K.); Liver Institute Northwest, Seattle (K.V.K.); the Division of Digestive Health and Liver Diseases, University of Miami, Miami (C.L.); the Liver Autoimmunity Unit, Hospital Italiano de Buenos Aires, Buenos Aires (A.V.); Centro de Investigación y Gastroenterología, Mexico City (A.L.L.G.C.); the Department of Basic Medical Sciences, Faculty of Public Health in Bytom, Medical University of Silesia, Bytom, Poland (E.J.); the Gastroenterology Institute, Tel Aviv Sourasky Medical Center, Israel and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel (E.Z.); the Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University, College of Medicine, Seongnam, South Korea (S.-H.J.); the Department of Gastroenterology, School of Medicine, Recep Tayyip Erdoğan University, Rize, Turkey (Y.Y.); Barts Liver Centre, Blizard Institute, Queen Mary University of London, London (Y.K.); the Reference Center for Inflammatory Biliary Diseases and Autoimmune Hepatitis, French Network for Rare Liver Disease in Children and Adults FILFOIE, European Reference Network RARE-LIVER, Saint-Antoine Hospital and Research Center, Assistance Publique-Hôpitaux de Paris, Sorbonne University, Paris (C.C.); Liver Centre Hamburg at Ifi-Institute, Hamburg, Germany (P.B.); the Division of Gastroenterology, Center for Autoimmune Liver Diseases, Department of Medicine and Surgery, University of Milan-Bicocca, and the European Reference Network on Hepatological Diseases (ERN RARE-LIVER), Fondazione IRCCS San Gerardo dei Tintori - both in Monza, Italy (P.I.); the Liver Unit, Hospital Clínic Barcelona, Fundació de Recerca Clínic Barcelona-Institut d'Investigacions Biomèdiques August Pi i Sunyer, CIBEREHD, European Reference Network on Hepatological Diseases (ERN-LIVER), University of Barcelona, Barcelona (M.C.L.H.); and Saberg Clinical Research, the Hague, the Netherlands (S.B.). Dr. Hirschfield is the Lily and Terry Horner Chair in Autoimmune Liver Disease Research at Toronto General Hospital.
Jazyk:	angličtina
Zdroj:	The New England journal of medicine [N Engl J Med] 2024 Feb 29; Vol. 390 (9), pp. 783-794. Date of Electronic Publication: 2024 Feb 21.
DOI:	10.1056/NEJMoa2312100
Abstrakt:	Background: Effective treatments for patients with primary biliary cholangitis are limited. Seladelpar, a peroxisome proliferator-activated receptor delta agonist, has potential benefits. Methods: In this phase 3, 12-month, double-blind, placebo-controlled trial, we randomly assigned (in a 2:1 ratio) patients who had had an inadequate response to or who had a history of unacceptable side effects with ursodeoxycholic acid to receive oral seladelpar at a dose of 10 mg daily or placebo. The primary end point was a biochemical response, which was defined as an alkaline phosphatase level less than 1.67 times the upper limit of the normal range, with a decrease of 15% or more from baseline, and a normal total bilirubin level at month 12. Key secondary end points were normalization of the alkaline phosphatase level at month 12 and a change in the score on the pruritus numerical rating scale (range, 0 [no itch] to 10 [worst itch imaginable]) from baseline to month 6 among patients with a baseline score of at least 4 (indicating moderate-to-severe pruritus). Results: Of the 193 patients who underwent randomization and treatment, 93.8% received ursodeoxycholic acid as standard-of-care background therapy. A greater percentage of the patients in the seladelpar group than in the placebo group had a biochemical response (61.7% vs. 20.0%; difference, 41.7 percentage points; 95% confidence interval [CI], 27.7 to 53.4, P<0.001). Normalization of the alkaline phosphatase level also occurred in a greater percentage of patients who received seladelpar than of those who received placebo (25.0% vs. 0%; difference, 25.0 percentage points; 95% CI, 18.3 to 33.2, P<0.001). Seladelpar resulted in a greater reduction in the score on the pruritus numerical rating scale than placebo (least-squares mean change from baseline, -3.2 vs. -1.7; least-squares mean difference, -1.5; 95% CI, -2.5 to -0.5, P = 0.005). Adverse events were reported in 86.7% of the patients in the seladelpar group and in 84.6% in the placebo group, and serious adverse events in 7.0% and 6.2%, respectively. Conclusions: In this trial involving patients with primary biliary cholangitis, the percentage of patients who had a biochemical response and alkaline phosphatase normalization was significantly greater with seladelpar than with placebo. Seladelpar also significantly reduced pruritus among patients who had moderate-to-severe pruritus at baseline. The incidence and severity of adverse events were similar in the two groups. (Funded by CymaBay Therapeutics; RESPONSE ClinicalTrials.gov number, NCT04620733; EudraCT number, 2020-004348-27.). (Copyright © 2024 Massachusetts Medical Society.)
Databáze:	MEDLINE
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