title: Long-term follow-up of patients with difficult to treat type 1 autoimmune hepatitis on Tacrolimus therapy.
abstract: BACKGROUND
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: a Liver Unit , University Hospital Birmingham NHS Trust , Birmingham , UK ;|b Centre for Liver Research and NIHR Biomedical Research Unit for Liver Disease, University of Birmingham , Birmingham , UK ;
authors.forename: Nwe Ni
authors.initials: NN
authors.lastname: Than
authors.affiliation: c Department of Medicine , University Medical Center Hamburg-Eppendorf , Hamburg , Germany.
authors.forename: Christiane
authors.initials: C
authors.lastname: Wiegard
authors.affiliation: c Department of Medicine , University Medical Center Hamburg-Eppendorf , Hamburg , Germany.
authors.forename: Christina
authors.initials: C
authors.lastname: Weiler-Normann
authors.affiliation: c Department of Medicine , University Medical Center Hamburg-Eppendorf , Hamburg , Germany.
authors.forename: Katja
authors.initials: K
authors.lastname: Füssel
authors.affiliation: a Liver Unit , University Hospital Birmingham NHS Trust , Birmingham , UK ;
authors.forename: Jake
authors.initials: J
authors.lastname: Mann
authors.affiliation: a Liver Unit , University Hospital Birmingham NHS Trust , Birmingham , UK ;
authors.forename: James
authors.initials: J
authors.lastname: Hodson
authors.affiliation: a Liver Unit , University Hospital Birmingham NHS Trust , Birmingham , UK ;|b Centre for Liver Research and NIHR Biomedical Research Unit for Liver Disease, University of Birmingham , Birmingham , UK ;
authors.forename: Gideon M
authors.initials: GM
authors.lastname: Hirschfield
authors.affiliation: c Department of Medicine , University Medical Center Hamburg-Eppendorf , Hamburg , Germany.
authors.forename: Ansgar W
authors.initials: AW
authors.lastname: Lohse
authors.affiliation: a Liver Unit , University Hospital Birmingham NHS Trust , Birmingham , UK ;|b Centre for Liver Research and NIHR Biomedical Research Unit for Liver Disease, University of Birmingham , Birmingham , UK ;
authors.forename: David H
authors.initials: DH
authors.lastname: Adams
authors.affiliation: c Department of Medicine , University Medical Center Hamburg-Eppendorf , Hamburg , Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Schramm
authors.affiliation: a Liver Unit , University Hospital Birmingham NHS Trust , Birmingham , UK ;|b Centre for Liver Research and NIHR Biomedical Research Unit for Liver Disease, University of Birmingham , Birmingham , UK ;
authors.forename: Ye Htun
authors.initials: YH
authors.lastname: Oo
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage; D001219:Aspartate Aminotransferases / Q000097:blood; D001379:Azathioprine / Q000627:therapeutic use; D015209:Cholangitis, Sclerosing / Q000150:complications; D016572:Cyclosporine / Q000627:therapeutic use; D005260:Female; D005500:Follow-Up Studies; D019693:Hepatitis, Autoimmune / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D015122:Mercaptopurine / Q000627:therapeutic use; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000031:analogs & derivatives / Q000627:therapeutic use; D011239:Prednisolone / Q000008:administration & dosage; D019233:Retreatment; D016559:Tacrolimus / Q000008:administration & dosage / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000893:Anti-Inflammatory Agents; D007074:Immunoglobulin G; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D011239:Prednisolone; D015122:Mercaptopurine; D001219:Aspartate Aminotransferases; D009173:Mycophenolic Acid; D001379:Azathioprine; D016559:Tacrolimus
keywords: Autoimmune hepatitis; Tacrolimus; immunoglobulins; treatment response