title: Outcomes in Pediatric Autoimmune Hepatitis and Significance of Azathioprine Metabolites.
abstract: Autoimmune hepatitis (AIH) is a common pediatric liver disease and long-term remission is usually maintained with azathioprine (AZA). There is no consensus on the target range for AZA active metabolite 6-thioguanine (6-TGN) levels in pediatric AIH. The aim of the present study was to characterize the outcomes of pediatric patients with AIH and determine correlations between AZA dosing or 6-TGN metabolite levels and biochemical remission.
  
  
  
  A retrospective chart review was performed and data on presentation, laboratories including AZA metabolite levels, medication use, and outcomes were collected.
  
  
  
  Between 2002 and 2013, 66 children with AIH were identified (mean age at diagnosis 9.6 ± 5.1 years) with a mean follow-up period of 2.9 ± 3.2 years. Common presenting symptoms included jaundice, fatigue, and abdominal pain. The majority of subjects received steroids for induction and AZA for maintenance of remission. Seventy-nine percent achieved biochemical remission (mean time to remission 6.2 ± 9.2 months), 14% were in the induction phase of therapy, 6% required liver transplantation, and 18% were weaned off immunosuppression and remained in remission. 6-TGN levels ranging from 50 to 250 pmol/8 × 10 red blood cell count were associated with biochemical remission (alanine aminotransferase levels of ≤50 U/L).
  
  
  
  The vast majority of children with AIH maintain a sustained remission with AZA monotherapy. Biochemical remission was maintained with 6-TGN levels much lower than that recommended for inflammatory bowel disease. These findings suggest that patients should be maintained at the lowest AZA dose possible that is associated with biochemical remission.
authors.affiliation: *Department of Pediatrics, University of Colorado School of Medicine†Digestive Health Institute, Children's Hospital Colorado‡Department of Pathology, University of Colorado School of Medicine§Department of Pathology, Children's Hospital Colorado||Department of Biostatistics and Informatics, University of Colorado School of Public Health, Aurora, CO.
authors.forename: Melissa A
authors.initials: MA
authors.lastname: Sheiko
authors.forename: Shikha S
authors.initials: SS
authors.lastname: Sundaram
authors.forename: Kelley E
authors.initials: KE
authors.lastname: Capocelli
authors.forename: Zhaoxing
authors.initials: Z
authors.lastname: Pan
authors.forename: Annette M
authors.initials: AM
authors.lastname: McCoy
authors.forename: Cara L
authors.initials: CL
authors.lastname: Mack
mesh_terms: D000293:Adolescent; D001379:Azathioprine / Q000378:metabolism / Q000493:pharmacokinetics* / Q000627:therapeutic use; D015415:Biomarkers / Q000097:blood; D002648:Child; D002675:Child, Preschool; D005260:Female; D005500:Follow-Up Studies; D019693:Hepatitis, Autoimmune / Q000097:blood / Q000188:drug therapy*; D006801:Humans; D007166:Immunosuppressive Agents / Q000378:metabolism / Q000493:pharmacokinetics* / Q000627:therapeutic use; D060828:Induction Chemotherapy; D060046:Maintenance Chemotherapy; D008297:Male; D012189:Retrospective Studies; D013866:Thioguanine / Q000097:blood*; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D007166:Immunosuppressive Agents; D013866:Thioguanine; D001379:Azathioprine