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Tacrolimus as an Effective and Durable Second-Line Treatment for Chronic Autoimmune Hepatitis: A Multicentric Study

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Abstract

Background

Autoimmune hepatitis (AIH) is a chronic liver disease able to progress to acute liver failure, cirrhosis, and liver cancer. A significant proportion of patients fail to first-line therapy or develop severe toxicity.

Aims

To assess safety and effectiveness of tacrolimus as a second-line therapy in AIH patients.

Methods

Multicentric retrospective study of AIH patients treated with tacrolimus for at least 3 months as a second-line therapy. Effectiveness was defined as complete normalization of transaminases and IgG.

Results

A total of 23 AIH patients were included in the final analysis. In 13% of patients tacrolimus was initiated because of toxicity to previous first-line treatments and the rest were switched because of previous non-efficacy. Tacrolimus was effective in 18 patients (78%; 95%CI: 55.20–91.92%). The median time receiving tacrolimus was 16 months (IQR 20). There was a sustained response with a significant improvement in all liver enzymes and IgG on last follow-up. Only one patient discontinued tacrolimus at the third month because of severe neuropathy, and ototoxicity. Responders were significantly older at diagnosis of AIH (41 ± 13 vs. 27 ± 10 years old; p = 0.0496).

Conclusion

Tacrolimus is effective and well tolerated as a second-line therapy in patients with AIH.

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Abbreviations

AEMPS:

Agencia Española de Medicamentos y Productos Sanitarios (Spanish Drug Agency)

AIH:

Autoimmune hepatitis

ALT:

Alanine aminotransferase

AP:

Alkaline phosphatase

AST:

Aspartate aminotransferase

EPA - OD:

Estudio Postautorización - Otros Diseños (Post-authorization study—other designs)

GGT:

Gamma-glutamyltransferase

HBV:

Hepatitis B virus

HCV:

Hepatitis C virus

HIV:

Human immunodeficiency virus

IgG:

Immunoglobulin G

INR:

International normalized ratio

IQR:

Interquartile range

mTOR:

Mammalian target of rapamycin

SD:

Standard deviation

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Funding

This is an independent study with no financial support.

Author information

Authors and Affiliations

  1. Gastroenterology and Hepatology Unit, Hospital Universitario Puerta de Hierro Majadahonda, Joaquin Rodrigo 1, Majadahonda, 28888, Madrid, Spain

    Carlos Ferre-Aracil, María Trapero-Marugán & José Luis Calleja

  2. Hepatology - Internal Medicine Unit, Hospital Universitario Vall d’Hebrón, Barcelona, Spain

    Mar Riveiro-Barciela & Patricia Álvarez-López

  3. Hepatology and Liver Transplantation Unit, Hospital Universitario Reina Sofía, IMBIC, CIBERehd, Córdoba, Spain

    Manuel Rodríguez-Perálvarez & Manuel de la Mata

  4. Liver Unit, Hospital Clínic de Barcelona, IDIBAPS, CIBERehd, Barcelona, Spain

    Laura-Patricia Llovet & María-Carlota Londoño

  5. Gastroenterology and Hepatology Unit, Hospital Universitario Ramón y Cajal, IRYCIS, CIBERehd, Universidad de Alcalá, Madrid, Spain

    Luis Téllez

  6. UGC Aparato Digestivo, Hospital Universitario Virgen del Rocío, Seville, Spain

    Yolanda Sánchez-Torrijos

  7. Gastroenterology and Hepatology Unit, Hospital Universitario Gregorio Marañón, Madrid, Spain

    Fernando Díaz-Fontenla, Magdalena Salcedo-Plaza & Rafael Bañares-Cañizares

  8. CIBERehd, Barcelona, Spain

    Mar Riveiro-Barciela

Authors
  1. Carlos Ferre-Aracil
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  2. Mar Riveiro-Barciela
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  3. María Trapero-Marugán
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  4. Manuel Rodríguez-Perálvarez
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  7. Yolanda Sánchez-Torrijos
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  8. Fernando Díaz-Fontenla
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  9. Magdalena Salcedo-Plaza
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  11. Manuel de la Mata
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  12. María-Carlota Londoño
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  13. Rafael Bañares-Cañizares
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  14. José Luis Calleja
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Corresponding author

Correspondence to Carlos Ferre-Aracil.

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Ferre-Aracil, C., Riveiro-Barciela, M., Trapero-Marugán, M. et al. Tacrolimus as an Effective and Durable Second-Line Treatment for Chronic Autoimmune Hepatitis: A Multicentric Study. Dig Dis Sci 66, 2826–2832 (2021). https://doi.org/10.1007/s10620-020-06569-9

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  • DOI: https://doi.org/10.1007/s10620-020-06569-9

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