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

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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.

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Authors and Affiliations

  1. Department of Gastroenterology, Hacettepe University, Ankara, Turkey

    Cumali Efe & Tugrul Purnak

  2. Department of Medicine, Cleveland Clinic Foundation, Cleveland, OH, USA

    Haider Al Taii

  3. Department of Hepatology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark

    Henriette Ytting & Fin Stolze Larsen

  4. Sektion Hepatologie, Klinik für Gastroenterologie und Rheumatologie, Universitätsklinikum Leipzig, Leipzig, Germany

    Niklas Aehling & Thomas Berg

  5. Division of Gastroenterology and Liver Unit, University of Alberta, Alberta, Canada

    Rahima A. Bhanji & Aldo J. Montano-Loza

  6. Hepatology Division, Centre for Digestive Diseases, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden

    Hannes Hagström & Staffan Wahlin

  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 Bologna, Bologna, Italy

    Luigi Muratori & Paolo Muratori

  8. Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden

    Mårten Werner

  9. Department of Molecular and Clinical Medicine, Skåne University Hospital, Lund, Sweden

    Daniel Klintman

  10. Division of Liver Diseases/Transplantation Institute, The Mount Sinai Medical Center, New York, USA

    Thomas D. Schiano

  11. Texas Liver Institute, San Antonio, TX, USA

    Naim Alkhouri

  12. Department of Gastroenterology, Numune Research and Education Hospital, Ankara, Turkey

    Ersan Ozaslan

  13. Institute of Liver Studies, King’s College Hospital NHS Foundation Trust, Denmark Hill, London, UK

    Daniel Klintman & Michael A. Heneghan

  14. Division of Gastroenterology, University of British Columbia and Vancouver General Hospital, Vancouver, Canada

    Eric M. Yoshida

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  1. Cumali Efe
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  2. Haider Al Taii
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Contributions

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.

Corresponding author

Correspondence to Cumali Efe.

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Efe, C., Taii, H.A., Ytting, H. et al. Tacrolimus and Mycophenolate Mofetil as Second-Line Therapies for Pediatric Patients with Autoimmune Hepatitis. Dig Dis Sci 63, 1348–1354 (2018). https://doi.org/10.1007/s10620-018-5011-x

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  • DOI: https://doi.org/10.1007/s10620-018-5011-x

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