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Digestive Diseases and Sciences

, Volume 63, Issue 5, pp 1348–1354 | Cite as

Tacrolimus and Mycophenolate Mofetil as Second-Line Therapies for Pediatric Patients with Autoimmune Hepatitis

  • 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
Original Article

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.

Keywords

Autoimmune hepatitis Mycophenolate mofetil Tacrolimus Second-line Cirrhosis Pediatric Liver transplantation 

Notes

Author’s contribution

SW and EMY share co-senior authorship. CE, SW, EMY, and EO conceptualized the study. CE, HY, HAT, HH, SW, and TP collected and analyzed the data and wrote the manuscript. RAB, NFM, LM, MW, FSL, PM, DK, TDS, NA, AJML, TB, and EO contributed data and approved the final manuscript. CE, EMY, MH, EO, and SW interpreted data and prepared manuscript for the final submission.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Cumali Efe
    • 1
  • Haider Al Taii
    • 2
  • Henriette Ytting
    • 3
  • Niklas Aehling
    • 4
  • Rahima A. Bhanji
    • 5
  • Hannes Hagström
    • 6
  • Tugrul Purnak
    • 1
  • Luigi Muratori
    • 7
  • Mårten Werner
    • 8
  • Paolo Muratori
    • 7
  • Daniel Klintman
    • 9
    • 13
  • Thomas D. Schiano
    • 10
  • Aldo J. Montano-Loza
    • 5
  • Thomas Berg
    • 4
  • Fin Stolze Larsen
    • 3
  • Naim Alkhouri
    • 11
  • Ersan Ozaslan
    • 12
  • Michael A. Heneghan
    • 13
  • Eric M. Yoshida
    • 14
  • Staffan Wahlin
    • 6
  1. 1.Department of GastroenterologyHacettepe UniversityAnkaraTurkey
  2. 2.Department of MedicineCleveland Clinic FoundationClevelandUSA
  3. 3.Department of Hepatology, RigshospitaletUniversity of CopenhagenCopenhagenDenmark
  4. 4.Sektion Hepatologie, Klinik für Gastroenterologie und RheumatologieUniversitätsklinikum LeipzigLeipzigGermany
  5. 5.Division of Gastroenterology and Liver UnitUniversity of AlbertaAlbertaCanada
  6. 6.Hepatology Division, Centre for Digestive DiseasesKarolinska Institutet and Karolinska University HospitalStockholmSweden
  7. 7.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 BolognaBolognaItaly
  8. 8.Department of Public Health and Clinical MedicineUmeå UniversityUmeåSweden
  9. 9.Department of Molecular and Clinical MedicineSkåne University HospitalLundSweden
  10. 10.Division of Liver Diseases/Transplantation InstituteThe Mount Sinai Medical CenterNew YorkUSA
  11. 11.Texas Liver InstituteSan AntonioUSA
  12. 12.Department of GastroenterologyNumune Research and Education HospitalAnkaraTurkey
  13. 13.Institute of Liver StudiesKing’s College Hospital NHS Foundation TrustLondonUK
  14. 14.Division of GastroenterologyUniversity of British Columbia and Vancouver General HospitalVancouverCanada

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