Cumali Efe1, Hannes Hagström2, Henriette Ytting3, Rahima A Bhanji4, Niklas F Müller5, Qixia Wang6, Tugrul Purnak7, Luigi Muratori8, Mårten Werner9, Hanns-Ulrich Marschall10, Paolo Muratori8, Fulya Gunşar11, Daniel Klintman12, Albert Parés13, Alexandra Heurgué-Berlot14, Thomas D Schiano15, Mustafa Cengiz16, Michele May-Sien Tana17, Xiong Ma6, Aldo J Montano-Loza4, Thomas Berg5, Sumita Verma18, Fin Stolze Larsen3, Ersan Ozaslan19, Michael A Heneghan20, Eric M Yoshida21, Staffan Wahlin2. 1. Department of Gastroenterology, Hacettepe University, Ankara, Turkey. Electronic address: drcumi21@hotmail.com. 2. Hepatology Division, Centre for Digestive Diseases, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden. 3. Department of Hepatology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark. 4. Division of Gastroenterology and Liver Unit, University of Alberta, Alberta, Canada. 5. Sektion Hepatologie, Klinik für Gastroenterologie und Rheumatologie, Universitätsklinikum Leipzig, Leipzig, Germany. 6. Division of Gastroenterology and Hepatology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Cancer Institute, Shanghai Institute of Digestive Disease, Shanghai, China. 7. Department of Gastroenterology, Hacettepe University, Ankara, Turkey. 8. Centro per lo Studio e la Cura delle Malattie Autoimmuni del Fegato e delle Vie Biliari, Dipartimento di Scienze Mediche e Chirurgiche, Alma Mater Studiorum, Università di Bologna, Bologna, Italy. 9. Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden. 10. Department of Molecular and Clinical Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden. 11. Department of Gastroenterology, Ege University, Bornova, Izmir, Turkey. 12. Department of Molecular and Clinical Medicine, Skåne University Hospital, Lund, Sweden; Division of Gastroenterology University of British Columbia, Vancouver General Hospital, Vancouver, Canada. 13. Liver Unit, Hospital Clínic, University of Barcelona, Barcelona, Spain. 14. Department of Hepato-Gastroenterology, Centre Hospitalier Universitaire Reims, Reims, France. 15. Division of Liver Diseases, The Mount Sinai Medical Center, New York, New York. 16. Department of Gastroenterology, Dr A.Y. Oncology Training and Research Hospital, Ankara, Turkey. 17. The Liver Center at University of California, San Francisco, Division of Gastroenterology, Department of Medicine, University of California, San Francisco, San Francisco, California. 18. Department of Medicine, Brighton and Sussex Medical School, Department of Gastroenterology and Hepatology, Brighton and Sussex University Hospital, Brighton, United Kingdom. 19. Department of Gastroenterology, Numune Research and Education Hospital, Ankara, Turkey. 20. Institute of Liver Studies, King's College Hospital National Health Service Foundation Trust, London, United Kingdom. 21. Division of Gastroenterology University of British Columbia, Vancouver General Hospital, Vancouver, Canada.
Abstract
BACKGROUND & AIMS: Predniso(lo)ne, alone or in combination with azathioprine, is the standard-of-care (SOC) therapy for autoimmune hepatitis (AIH). However, the SOC therapy is poorly tolerated or does not control disease activity in up to 20% of patients. We assessed the efficacy of mycophenolate mofetil (MMF) and tacrolimus as second-line therapy for patients with AIH. METHODS: We performed a retrospective study of data (from 19 centers in Europe, the United States, Canada, and China) from 201 patients with AIH who received second-line therapy (121 received MMF and 80 received tacrolimus), for a median of 62 months (range, 6-190 mo). Patients were categorized according to their response to SOC. Patients in group 1 (n = 108) had a complete response to the SOC, but were switched to second-line therapy as a result of side effects of predniso(lo)ne or azathioprine, whereas patients in group 2 (n = 93) had not responded to SOC. RESULTS: There was no significant difference in the proportion of patients with a complete response to MMF (69.4%) vs tacrolimus (72.5%) (P = .639). In group 1, MMF and tacrolimus maintained a biochemical remission in 91.9% and 94.1% of patients, respectively (P = .682). Significantly more group 2 patients given tacrolimus compared with MMF had a complete response (56.5% vs 34%, respectively; P = .029) There were similar proportions of liver-related deaths or liver transplantation among patients given MMF (13.2%) vs tacrolimus (10.3%) (log-rank, P = .472). Ten patients receiving MMF (8.3%) and 10 patients receiving tacrolimus (12.5%) developed side effects that required therapy withdrawal. CONCLUSIONS: Long-term therapy with MMF or tacrolimus generally was well tolerated by patients with AIH. The agents were equally effective in previous complete responders who did not tolerate SOC therapy. Tacrolimus led to a complete response in a greater proportion of previous nonresponder patients compared with MMF.
BACKGROUND & AIMS:Predniso(lo)ne, alone or in combination with azathioprine, is the standard-of-care (SOC) therapy for autoimmune hepatitis (AIH). However, the SOC therapy is poorly tolerated or does not control disease activity in up to 20% of patients. We assessed the efficacy of mycophenolate mofetil (MMF) and tacrolimus as second-line therapy for patients with AIH. METHODS: We performed a retrospective study of data (from 19 centers in Europe, the United States, Canada, and China) from 201 patients with AIH who received second-line therapy (121 received MMF and 80 received tacrolimus), for a median of 62 months (range, 6-190 mo). Patients were categorized according to their response to SOC. Patients in group 1 (n = 108) had a complete response to the SOC, but were switched to second-line therapy as a result of side effects of predniso(lo)ne or azathioprine, whereas patients in group 2 (n = 93) had not responded to SOC. RESULTS: There was no significant difference in the proportion of patients with a complete response to MMF (69.4%) vs tacrolimus (72.5%) (P = .639). In group 1, MMF and tacrolimus maintained a biochemical remission in 91.9% and 94.1% of patients, respectively (P = .682). Significantly more group 2 patients given tacrolimus compared with MMF had a complete response (56.5% vs 34%, respectively; P = .029) There were similar proportions of liver-related deaths or liver transplantation among patients given MMF (13.2%) vs tacrolimus (10.3%) (log-rank, P = .472). Ten patients receiving MMF (8.3%) and 10 patients receiving tacrolimus (12.5%) developed side effects that required therapy withdrawal. CONCLUSIONS: Long-term therapy with MMF or tacrolimus generally was well tolerated by patients with AIH. The agents were equally effective in previous complete responders who did not tolerate SOC therapy. Tacrolimus led to a complete response in a greater proportion of previous nonresponder patients compared with MMF.
Authors: Cumali Efe; Haider Al Taii; Henriette Ytting; Niklas Aehling; Rahima A Bhanji; Hannes Hagström; Tugrul Purnak; Luigi Muratori; Mårten Werner; Paolo Muratori; Daniel Klintman; Thomas D Schiano; Aldo J Montano-Loza; Thomas Berg; Fin Stolze Larsen; Naim Alkhouri; Ersan Ozaslan; Michael A Heneghan; Eric M Yoshida; Staffan Wahlin Journal: Dig Dis Sci Date: 2018-03-22 Impact factor: 3.199
Authors: Nwe Ni Than; James Hodson; Daniel Schmidt-Martin; Richard Taubert; Rebecca E Wawman; Meemee Botter; Nishant Gautam; Kilian Bock; Rebecca Jones; Gautham D Appanna; Andrew Godkin; Aldo J Montano-Loza; Frank Lammert; Christoph Schramm; Michael P Manns; Mark Swain; Kelly W Burak; David H Adams; Gideon M Hirschfield; Ye Htun Oo Journal: JHEP Rep Date: 2019-11-05
Authors: Simon Pape; Frederik Nevens; Chris Verslype; Caroline Mertens; Joost P H Drenth; Eric T T L Tjwa Journal: Eur J Gastroenterol Hepatol Date: 2020-06 Impact factor: 2.586