title: Fulminant hepatic failure of autoimmune aetiology in children.
abstract: OBJECTIVE
  Autoimmune hepatitis (AIH) is considered an underdiagnosed cause of fulminant hepatic failure (FHF). Autoimmune FHF (AI-FHF) is believed to lead invariably to liver transplantation (LTX) or death. We aimed to describe the autoimmune features of children diagnosed as having AI-FHF and indeterminate FHF (ID-FHF), and describe the outcome of patients with AI-FHF treated with immunosuppressive drugs.
  
  
  METHODS
  In this case-control study, the files of patients with AI-FHF and ID-FHF were reviewed and compared. AIH was diagnosed based on positive autoantibodies, raised immunoglobulin G, and histology when available. FHF was defined by raised transaminases, international normalised ratio ≥ 2.0, presence of encephalopathy, and no previously recognised liver disease.
  
  
  RESULTS
  A total of 46 children with FHF were managed in the last 15 years: 10/46 (22%) had AI-FHF, 20/46 (43%) ID-FHF, and 16 had other diagnosis. The mean follow-up time was 4.6 years. AI-FHF and ID-FHF differed for the presence of autoantibodies (10/10, 6/10 liver/kidney microsome [LKM]-type, vs 3/20, none LKM, P < 0.0001), immunoglobulin G level (1845 vs 880 mg/dL, P < 0.001), median age at diagnosis (6.4 vs 1.8 years, P = 0.017), and alanine aminotransferase level (1020 vs 2386 IU/L, P = 0.029). Liver histology did not allow to differentiate the 2 conditions. Among the patients with AI-FHF, 4/9 who received steroids recovered; 5/9 required LTX and 1 died awaiting treatment.
  
  
  CONCLUSIONS
  AIH is a much more common cause of FHF than previously suggested, and a complete autoantibody testing including LKM-type is essential in this setting. Autoantibodies are uncommon in ID-FHF, and histology cannot distinguish it from AI-FHF. A cautious steroid trial may avoid LTX in some of the patients with AI-FHF.
authors.affiliation: *Paediatric Hepatology, Gastroenterology and Transplantation †Paediatric Intensive Care Unit ‡Laboratory Medicine §Transplant Pathology, Hospital Papa Giovanni XXIII, Bergamo, Italy ||Pathology Department, Institute of Liver Studies King's College Hospital, London, UK ¶General Surgery and Transplantation, Hospital Papa Giovanni XXIII, Bergamo, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Di Giorgio
authors.forename: M
authors.initials: M
authors.lastname: Bravi
authors.forename: E
authors.initials: E
authors.lastname: Bonanomi
authors.forename: G
authors.initials: G
authors.lastname: Alessio
authors.forename: A
authors.initials: A
authors.lastname: Sonzogni
authors.forename: Y
authors.initials: Y
authors.lastname: Zen
authors.forename: M
authors.initials: M
authors.lastname: Colledan
authors.forename: L
authors.initials: L
authors.lastname: D'Antiga
mesh_terms: D000293:Adolescent; D000367:Age Factors; D000410:Alanine Transaminase / Q000097:blood; D000974:Antibodies, Antinuclear / Q000097:blood; D001323:Autoantibodies / Q000097:blood; D001379:Azathioprine / Q000627:therapeutic use; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D016572:Cyclosporine / Q000627:therapeutic use; D005500:Follow-Up Studies; D019693:Hepatitis, Autoimmune / Q000150:complications*; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007223:Infant; D017114:Liver Failure, Acute / Q000209:etiology* / Q000473:pathology / Q000628:therapy*; D016031:Liver Transplantation; D008775:Methylprednisolone / Q000627:therapeutic use; D012189:Retrospective Studies; D015996:Survival Rate
chemical_list: D000974:Antibodies, Antinuclear; D001323:Autoantibodies; D007074:Immunoglobulin G; D007166:Immunosuppressive Agents; C060729:anti-liver kidney microsome antibody; D016572:Cyclosporine; D000410:Alanine Transaminase; D001379:Azathioprine; D008775:Methylprednisolone