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

Scand J Gastroenterol. 2016 Mar;51(3):329-36. doi: 10.3109/00365521.2015.1095351. Epub 2015 Oct 12.

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; Tacrolimus; immunoglobulins; treatment response.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Anti-Inflammatory Agents / administration & dosage
  • Aspartate Aminotransferases / blood
  • Azathioprine / therapeutic use
  • Cholangitis, Sclerosing / complications
  • Cyclosporine / therapeutic use
  • Female
  • Follow-Up Studies
  • Hepatitis, Autoimmune / blood
  • Hepatitis, Autoimmune / complications
  • Hepatitis, Autoimmune / drug therapy*
  • Humans
  • Immunoglobulin G / blood
  • Immunosuppressive Agents / administration & dosage
  • Immunosuppressive Agents / therapeutic use*
  • Male
  • Mercaptopurine / therapeutic use
  • Middle Aged
  • Mycophenolic Acid / analogs & derivatives
  • Mycophenolic Acid / therapeutic use
  • Prednisolone / administration & dosage
  • Retreatment
  • Tacrolimus / administration & dosage
  • Tacrolimus / therapeutic use*
  • Time Factors
  • Treatment Outcome
  • Young Adult

Substances

  • Anti-Inflammatory Agents
  • Immunoglobulin G
  • Immunosuppressive Agents
  • Cyclosporine
  • Prednisolone
  • Mercaptopurine
  • Aspartate Aminotransferases
  • Mycophenolic Acid
  • Azathioprine
  • Tacrolimus