Cumali Efe1, Haider Al Taii2, Henriette Ytting3, Niklas Aehling4, Rahima A Bhanji5, Hannes Hagström6, Tugrul Purnak7, Luigi Muratori8, Mårten Werner9, Paolo Muratori8, Daniel Klintman10,11, Thomas D Schiano12, Aldo J Montano-Loza5, Thomas Berg4, Fin Stolze Larsen3, Naim Alkhouri13, Ersan Ozaslan14, Michael A Heneghan11, Eric M Yoshida15, Staffan Wahlin6. 1. Department of Gastroenterology, Hacettepe University, Ankara, Turkey. drcumi21@hotmail.com. 2. Department of Medicine, Cleveland Clinic Foundation, Cleveland, OH, USA. 3. Department of Hepatology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark. 4. Sektion Hepatologie, Klinik für Gastroenterologie und Rheumatologie, Universitätsklinikum Leipzig, Leipzig, Germany. 5. Division of Gastroenterology and Liver Unit, University of Alberta, Alberta, Canada. 6. Hepatology Division, Centre for Digestive Diseases, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden. 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 (DIMEC), 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, Skåne University Hospital, Lund, Sweden. 11. Institute of Liver Studies, King's College Hospital NHS Foundation Trust, Denmark Hill, London, UK. 12. Division of Liver Diseases/Transplantation Institute, The Mount Sinai Medical Center, New York, USA. 13. Texas Liver Institute, San Antonio, TX, USA. 14. Department of Gastroenterology, Numune Research and Education Hospital, Ankara, Turkey. 15. Division of Gastroenterology, University of British Columbia and Vancouver General Hospital, Vancouver, Canada.
Abstract
BACKGROUND: We studied the efficacy and safety of mycophenolate mofetil (MMF) and tacrolimus as second-line therapy in pediatric patients with autoimmune hepatitis (AIH) who were intolerant or non-responders to standard therapy (corticosteroid and azathioprine). PATIENTS AND METHODS: We performed a retrospective study of data from 13 centers in Europe, USA, and Canada. Thirty-eight patients (< 18 years old) who received second-line therapy (18 MMF and 20 tacrolimus), for a median of 72 months (range 8-182) were evaluated. Patients were categorized into two groups: Group 1 (n = 17) were intolerant to corticosteroid or azathioprine, and group 2 (n = 21) were non-responders to standard therapy. RESULTS: Overall complete response rates were similar in patients treated with MMF and tacrolimus (55.6 vs. 65%, p = 0.552). In group 1, MMF and tacrolimus maintained a biochemical remission in 88.9 and 87.5% of patients, respectively (p = 0.929). More patients in group 2 given tacrolimus compared to MMF had a complete response, but the difference was not statistically significant (50.0 vs. 22.2%, p = 0.195). Biochemical remission was achieved in 71.1% (27/38) of patients by tacrolimus and/or MMF. Decompensated cirrhosis was more commonly seen in MMF and/or tacrolimus non-responders than in responders (45.5 vs. 7.4%, p = 0.006). Five patients who received second-line therapy (2 MMF and 3 tacrolimus) developed side effects that led to therapy withdrawal. CONCLUSIONS: Long-term therapy with MMF or tacrolimus was generally well tolerated by pediatric patients with AIH. Both MMF and tacrolimus had excellent efficacy in patients intolerant to corticosteroid or azathioprine. Tacrolimus might be more effective than MMF in patients failing previous therapy.
BACKGROUND: We studied the efficacy and safety of mycophenolate mofetil (MMF) and tacrolimus as second-line therapy in pediatric patients with autoimmune hepatitis (AIH) who were intolerant or non-responders to standard therapy (corticosteroid and azathioprine). PATIENTS AND METHODS: We performed a retrospective study of data from 13 centers in Europe, USA, and Canada. Thirty-eight patients (< 18 years old) who received second-line therapy (18 MMF and 20 tacrolimus), for a median of 72 months (range 8-182) were evaluated. Patients were categorized into two groups: Group 1 (n = 17) were intolerant to corticosteroid or azathioprine, and group 2 (n = 21) were non-responders to standard therapy. RESULTS: Overall complete response rates were similar in patients treated with MMF and tacrolimus (55.6 vs. 65%, p = 0.552). In group 1, MMF and tacrolimus maintained a biochemical remission in 88.9 and 87.5% of patients, respectively (p = 0.929). More patients in group 2 given tacrolimus compared to MMF had a complete response, but the difference was not statistically significant (50.0 vs. 22.2%, p = 0.195). Biochemical remission was achieved in 71.1% (27/38) of patients by tacrolimus and/or MMF. Decompensated cirrhosis was more commonly seen in MMF and/or tacrolimus non-responders than in responders (45.5 vs. 7.4%, p = 0.006). Five patients who received second-line therapy (2 MMF and 3 tacrolimus) developed side effects that led to therapy withdrawal. CONCLUSIONS: Long-term therapy with MMF or tacrolimus was generally well tolerated by pediatric patients with AIH. Both MMF and tacrolimus had excellent efficacy in patients intolerant to corticosteroid or azathioprine. Tacrolimus might be more effective than MMF in patients failing previous therapy.
Authors: Michael P Manns; Albert J Czaja; James D Gorham; Edward L Krawitt; Giorgina Mieli-Vergani; Diego Vergani; John M Vierling Journal: Hepatology Date: 2010-06 Impact factor: 17.425
Authors: T Sahutoglu; S U Akgul; Y Caliskan; H Yazici; E Demir; E Kara; S Temurhan; F O Savran; A Turkmen Journal: Transplant Proc Date: 2017-04 Impact factor: 1.066
Authors: Cumali Efe; Hannes Hagström; Henriette Ytting; Rahima A Bhanji; Niklas F Müller; Qixia Wang; Tugrul Purnak; Luigi Muratori; Mårten Werner; Hanns-Ulrich Marschall; Paolo Muratori; Fulya Gunşar; Daniel Klintman; Albert Parés; Alexandra Heurgué-Berlot; Thomas D Schiano; Mustafa Cengiz; Michele May-Sien Tana; Xiong Ma; Aldo J Montano-Loza; Thomas Berg; Sumita Verma; Fin Stolze Larsen; Ersan Ozaslan; Michael A Heneghan; Eric M Yoshida; Staffan Wahlin Journal: Clin Gastroenterol Hepatol Date: 2017-06-08 Impact factor: 11.382
Authors: Harpreet K Dhaliwal; Barbara S Hoeroldt; Asha K Dube; Elaine McFarlane; James C E Underwood; Mohammed A Karajeh; Dermot Gleeson Journal: Am J Gastroenterol Date: 2015-05-26 Impact factor: 10.864
Authors: Fin Stolze Larsen; Ben Vainer; Martin Eefsen; Peter Nissen Bjerring; Bent Adel Hansen Journal: World J Gastroenterol Date: 2007-06-21 Impact factor: 5.742