De-novo autoimmune hepatitis after liver transplantation

Lancet. 1998 Feb 7;351(9100):409-13. doi: 10.1016/S0140-6736(97)06478-7.


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.

Findings: 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.

Interpretation: 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.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Inflammatory Agents / therapeutic use
  • Autoantibodies / blood
  • Azathioprine / therapeutic use
  • Child
  • Female
  • Graft Survival
  • Hepatitis, Autoimmune / diagnosis*
  • Hepatitis, Autoimmune / immunology
  • Hepatitis, Autoimmune / therapy
  • Humans
  • Immunoglobulin G / blood
  • Immunosuppression
  • Immunosuppressive Agents / therapeutic use
  • Liver / pathology
  • Liver Transplantation*
  • Male
  • Postoperative Complications / diagnosis*
  • Postoperative Complications / immunology
  • Postoperative Complications / therapy
  • Prednisolone / therapeutic use
  • Time Factors


  • Anti-Inflammatory Agents
  • Autoantibodies
  • Immunoglobulin G
  • Immunosuppressive Agents
  • Prednisolone
  • Azathioprine