title: Everolimus treatment for patients with autoimmune hepatitis and poor response to standard therapy and drug alternatives in use.
abstract: OBJECTIVE
  Not all patients with autoimmune hepatitis (AIH) respond to standard medical therapy with corticosteroids and azathioprine. Such patients may develop end-stage liver disease with poor prognosis unless transplantation is considered. Alternatively, the introduction of new therapeutic strategies could potentially ameliorate deterioration of liver function. Patients in our tertiary center were selected for everolimus therapy when exhibiting nonresponse or intolerance to combinations of the standard and empirical drugs in use (e.g., mycophenolate mofetil, calcineurin inhibitors [CNIs]). We here report the efficacy of everolimus treatment of patients with AIH.
  
  
  METHODS
  Seven patients (six female, mean age 47 years, range 22-62 years) in whom disease control could not be achieved with standard therapy or the alternative drugs in use were included.
  
  
  RESULTS
  Treatment with everolimus induced a clear reduction of transaminases within 2 weeks. After 3-5 months three patients had normal alanine aminotransferase (ALT) levels (10-45 IU) and four patients had ALT levels below 55 IU compared to a three- to fivefold elevated level prior to everolimus treatment. Sustained remission after 1 year of treatment was observed in three patients; in another two patients ALT was 45-68 U/L. Four patients in remission after 3 years were rebiopsied. Two showed no histological progression, and in two the fibrosis had decreased. Side effects noted were myalgias and minor bacterial infections not leading to discontinuation of the drug.
  
  
  CONCLUSIONS
  Our experience indicates that everolimus may be of value in selected patients with therapy-resistant AIH and comorbidity/side effects that excludes the use of CNIs.
authors: Department of Hepatology A-2121, Rigshospitalet, University of Copenhagen , Copenhagen , Denmark.
authors: Henriette
authors: H
authors: Ytting
authors: Fin Stolze
authors: FS
authors: Larsen
mesh_terms: D000305:Adrenal Cortex Hormones / Q000627:therapeutic use; D000328:Adult; D000410:Alanine Transaminase / Q000097:blood*; D001379:Azathioprine / Q000627:therapeutic use; D018432:Drug Resistance, Multiple / Q000276:immunology*; D000068338:Everolimus / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D019693:Hepatitis, Autoimmune / Q000188:drug therapy*; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D008111:Liver Function Tests; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000031:analogs & derivatives / Q000627:therapeutic use; D012074:Remission Induction; D062606:Tertiary Care Centers; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000305:Adrenal Cortex Hormones; D007166:Immunosuppressive Agents; D000068338:Everolimus; D000410:Alanine Transaminase; D009173:Mycophenolic Acid; D001379:Azathioprine
keywords: alternative treatment; autoimmune hepatitis; everolimus; mammalian target of rapamycin inhibitor; nonresponse; poor response; treatment