Long-term follow-up of patients with difficult to treat type 1 autoimmune hepatitis on Tacrolimus therapy

ABSTRACT

Introduction: Autoimmune hepatitis (AIH) is an immune-mediated liver disease, which requires long-term immunosuppression. Ten to fifteen percent of patients experience insufficient/intolerance response to standard therapy. Although alternate immunosuppression has been applied, there is little long-term data reported on safety, efficacy, steroid-dose reduction and disease evolution in patients with difficult AIH who were on Tacrolimus therapy. Materials and methods: Clinical, biochemical, immunological profiles, treatment response and side effects of 17 AIH patients treated with Tacrolimus between 2003 and 2014 were analyzed from two tertiary referral liver centers. Results: Tacrolimus was started on 16/17 (94%) patients due to insufficient response to standard therapy. The median duration of treatment was 24 months and patients were followed up for median of 60 months. Tacrolimus dosage was 2 mg/day (median). During first year of therapy, there was a significant improvement in immunoglobulin G and Aspartate transaminase level. 9/17 (52%) compliant and definite AIH patients remained on Tacrolimus at end of follow-up and prednisolone dose reduction was achieved from 10 to 5 mg. All patients are alive and one patient underwent liver transplantation. 4/17 (24%) patients developed overlap with primary sclerosing cholangitis over follow-up period. No significant side effects were observed with Tacrolimus therapy. Conclusion: Tacrolimus could be used in compliant patients with difficult to treat AIH in experienced centers. Its use is safe and can improve liver biochemistry, IgG and reduce steroid requirement. However, due to the lack of immunomodulatory effect, unmet need for effective immune-regulatory therapies still remain for AIH patients.

KEYWORDS:

• Autoimmune hepatitis
• immunoglobulins
• Tacrolimus
• treatment response

Acknowledgements

We thank all medical colleagues and histopathology colleagues that were involvement in diagnosis, treatment and follow up of patients.

Declaration of interest

The authors report no conflict of interest. Dr. Ye Hun Oo was funded by “Medical Research Council Clinician Scientist grant”, UHB charity grant. Dr. Nwe Ni Than was funded by National Institute for Health Research (NIHR) Liver BRU Birmingham. Professor Christoph Schramm was supported by the “YAEL-foundation and the Deutsche Forschungsgemeinschaft, SFB841, and the Dr. Helmut und Hannelore Greve Foundation”. This research was supported by the National Institute for Health Research (NIHR) Liver Biomedical Research Unit (NIHR BRU) based at University Hospital Birmingham NHS Trust and University of Birmingham. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health.