title: Seronegative autoimmune hepatitis in children: Spectrum of disorders.
abstract: BACKGROUND
  A few children with acute or chronic liver disease display histological features compatible with autoimmune hepatitis, but lack specific serological markers.
  
  
  OBJECTIVE
  To describe features, management and outcome of childhood seronegative autoimmune hepatitis.
  
  
  METHODS
  From 1988 to 2010, 38 children were included under the following criteria: negative virological studies, no serum autoantibodies, exclusion of other causes of liver diseases, and liver histology compatible with autoimmune hepatitis.
  
  
  RESULTS
  Four groups were identified: (1) 12 with increased serum gamma globulin concentrations; (2) 10 with normal or low serum gamma globulins and no combined blood disease; (3) 10 with combined aplastic anemia; and (4) 6 with peripheral thrombocytopenia with/without neutropenia. Immunosuppressive treatment was associated with aminotransferases normalization in all but one child who required liver transplantation. Relapses occurred in 10 children. Lymphocytopenia was found at the time of the diagnosis of hepatitis in 13 children, 12 in groups 3 or 4. All 38 children are alive after 4-17 years, 18 still under immunosuppression.
  
  
  CONCLUSIONS
  Childhood seronegative autoimmune hepatitis includes a spectrum of disorders. Early liver histology is recommended and, if compatible with autoimmune hepatitis, immunosuppressive treatment should be started. Initial lymphocytopenia may indicate future hematological complication.
authors.affiliation: Dipartimento di Medicina Clinica e Sperimentale, Università di Pisa, Gastroenterologia Pediatrica, Azienda Ospedaliera Universitaria Pisana, Pisa, Italy; Epatologia Pediatrica e Trapianto di fegato, ISMETT, University of Pittsburgh Medical Center, Palermo, Italy. Electronic address: giuseppe.maggiore@med.unipi.it.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Maggiore
authors.affiliation: Hématologie/Greffe de Moelle, INSERM U 1160 AP-HP, Université Paris VII, Hôpital Saint Louis, Paris, France.
authors.forename: Gérard
authors.initials: G
authors.lastname: Socie
authors.affiliation: Epatologia Pediatrica e Trapianto di fegato, ISMETT, University of Pittsburgh Medical Center, Palermo, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Sciveres
authors.affiliation: Virologie, AP-HP, Hôpital Paul Brousse Villejuif, France.
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Roque-Afonso
authors.affiliation: Dipartimento di Medicina Clinica e Sperimentale, Università di Pisa, Gastroenterologia Pediatrica, Azienda Ospedaliera Universitaria Pisana, Pisa, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Nastasio
authors.affiliation: Autoimmunité, AP-HP, Hôpital Saint Antoine, Paris, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Johanet
authors.affiliation: Gastroentérologie, Hépatologie, et Nutrition, INSERM U 995, Hôpital Jeanne de Flandre, Lille, France.
authors.forename: Fréderic
authors.initials: F
authors.lastname: Gottrand
authors.affiliation: Hépatogastroentérologie et Nutrition Pédiatriques, Hôpital Arnaud de Villeneuve, Montpellier, France.
authors.forename: Sébastien
authors.initials: S
authors.lastname: Fournier-Favre
authors.affiliation: Hépatologie Pédiatrique et Centre de référence national de l'atrésie des voies biliaires, Hôpital Bicêtre, AP-HP, Université Paris-Sud 11, Le Kremlin Bicêtre, France; Inserm U 757, Université Paris-Sud 11, Orsay, France.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Jacquemin
authors.affiliation: Hépatologie Pédiatrique et Centre de référence national de l'atrésie des voies biliaires, Hôpital Bicêtre, AP-HP, Université Paris-Sud 11, Le Kremlin Bicêtre, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Bernard
mesh_terms: D000293:Adolescent; D000741:Anemia, Aplastic / Q000453:epidemiology; D001323:Autoantibodies / Q000097:blood; D002648:Child; D002675:Child, Preschool; D005260:Female; D005602:France; D019693:Hepatitis, Autoimmune / Q000097:blood* / Q000150:complications* / Q000628:therapy*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007223:Infant; D007558:Italy; D008099:Liver / Q000473:pathology; D017093:Liver Failure / Q000453:epidemiology; D016031:Liver Transplantation; D008297:Male; D013921:Thrombocytopenia / Q000453:epidemiology; D000637:Transaminases / Q000097:blood; D055545:gamma-Globins / Q000032:analysis*
chemical_list: D001323:Autoantibodies; D007166:Immunosuppressive Agents; D055545:gamma-Globins; D000637:Transaminases
keywords: Autoantibody-negative autoimmune hepatitis; Liver failure; Liver transplantation; Severe aplastic anemia