title: De-novo autoimmune hepatitis after liver transplantation.
abstract: BACKGROUND
  Late graft dysfunction that does not result from recognised causes, such as rejection, infection, or vascular or biliary complications, can occur after liver transplantation. We investigated a particular type of unexplained graft dysfunction that is associated with autoimmune features in children who underwent transplantation at our unit between 1991 and 1996.
  
  
  METHODS
  Seven (4%) of 180 liver-transplant recipients developed an unexplained but characteristic form of graft dysfunction (five boys, two girls; median age at presentation 10.3 years, range 2.0-19.4). The median period after surgery was 24 months (6-45). The indications for transplantation had been extrahepatic biliary atresia (four patients), Alagille's syndrome (one), drug-induced acute liver failure (one), and alpha1-antitrypsin deficiency (one). Four patients were on triple immunosuppression with cyclosporin, azathioprine, and prednisolone; and three were on tacrolimus. Immunoglobulin measurements, autoantibody studies, serological studies, and HLA typing were undertaken. Liver-biopsy samples were taken.
  
  
  RESULTS
  Infectious and surgical complications were excluded. Liver-biopsy samples showed the histological changes of chronic hepatitis, including portal and periportal hepatitis with lymphocytes and plasma cells, bridging collapse, and perivenular-cell necrosis without changes typical of acute or chronic rejection. All patients had high concentrations of IgG (median 22 g/L [range 17.2-34.4]) and high titres of autoantibodies. All but one patient responded to prednisolone 2 mg/kg daily and an increase in or addition of azathioprine (1.5 mg/kg daily) within a median of 32 days (7-316). One responder relapsed owing to poor compliance but went into remission after treatment was restored. All six respondents remain in remission on a reduced dose of prednisolone (5-10 mg/day) and 1.5 mg/kg daily azathioprine at a median of 283 days (range 108-730) follow-up.
  
  
  CONCLUSIONS
  Our data show that symptoms of autoimmune hepatitis, which are responsive to the classical treatment for this condition, can appear in liver-transplant patients while they are on anti-rejection immunosuppression. Whether the liver damage in these patients is a form of rejection or the consequence of autoimmune attack has yet to be established.
authors.affiliation: Department of Child Health, King's College Hospital, London, UK.
authors.forename: N
authors.initials: N
authors.lastname: Kerkar
authors.forename: N
authors.initials: N
authors.lastname: Hadzić
authors.forename: E T
authors.initials: ET
authors.lastname: Davies
authors.forename: B
authors.initials: B
authors.lastname: Portmann
authors.forename: P T
authors.initials: PT
authors.lastname: Donaldson
authors.forename: M
authors.initials: M
authors.lastname: Rela
authors.forename: N D
authors.initials: ND
authors.lastname: Heaton
authors.forename: D
authors.initials: D
authors.lastname: Vergani
authors.forename: G
authors.initials: G
authors.lastname: Mieli-Vergani
mesh_terms: D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D001323:Autoantibodies / Q000097:blood; D001379:Azathioprine / Q000627:therapeutic use; D002648:Child; D005260:Female; D006085:Graft Survival; D019693:Hepatitis, Autoimmune / Q000175:diagnosis* / Q000276:immunology / Q000628:therapy; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D007165:Immunosuppression Therapy; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D008099:Liver / Q000473:pathology; D016031:Liver Transplantation; D008297:Male; D011183:Postoperative Complications / Q000175:diagnosis* / Q000276:immunology / Q000628:therapy; D011239:Prednisolone / Q000627:therapeutic use; D013997:Time Factors
chemical_list: D000893:Anti-Inflammatory Agents; D001323:Autoantibodies; D007074:Immunoglobulin G; D007166:Immunosuppressive Agents; D011239:Prednisolone; D001379:Azathioprine