Development of cytochrome P450 2D6-specific LKM-autoantibodies following liver transplantation for Wilson's disease -- possible association with a steroid-resistant transplant rejection episode

J Hepatol. 1999 Jul;31(1):149-55. doi: 10.1016/s0168-8278(99)80175-5.


Background/aims: Antibodies to cytochrome P450 2D6, also known as LKM1-autoantibodies, are characteristic for a subgroup of patients with autoimmune hepatitis, but can also occasionally be found in hepatitis C. We observed the occurrence of LKM1-autoantibodies 4 months after liver transplantation for Wilson's disease, in close association with a steroid-resistant rejection episode, in the absence of evidence for autoimmune hepatitis or hepatitis C.

Methods: Sera from several time points prior to and following transplantation were tested for LKM-reactivity by immunofluorescence, ELISA and Western blotting. Antigen specificity was confirmed by Western blotting analysis on different cytochrome P450 isoenzymes. The absence of viral hepatitis C and hepatitis G virus infection was confirmed by polymerase chain reaction. The serum of the organ donor was also tested.

Results: All the sera prior to transplantation and up to 4 months after transplantation were LKM-negative by all assay systems used. In the course of a steroid-resistant rejection episode at this time, the patient developed LKM antibodies at high titre (70% in inhibition ELISA) and has remained positive since (now more than 4 years). Reactivity was exclusively to the cytochrome isoenzyme 2D6. Hepatitis C infection never occurred, but hepatitis G was transiently present many years prior to transplantation. The donor serum was negative for all autoantibodies and for hepatitis C and G virus infection.

Discussion: We here describe a patient developing LKM1-autoantibodies without evidence of autoimmune or viral hepatitis. The close temporal association with a transplant rejection episode suggests immunological mechanisms of rejection together with hepatocellular injury as a pathogenetic mechanism.

Publication types

  • Case Reports

MeSH terms

  • Adult
  • Antibody Specificity
  • Autoantibodies / analysis*
  • Azathioprine / therapeutic use
  • Cyclosporine / therapeutic use
  • Cytochrome P-450 CYP2D6 / immunology*
  • Drug Resistance
  • Enzyme-Linked Immunosorbent Assay
  • Graft Rejection / drug therapy
  • Graft Rejection / immunology*
  • Hepatolenticular Degeneration / surgery*
  • Humans
  • Immunosuppressive Agents / therapeutic use*
  • Kidney / immunology
  • Kidney / pathology
  • Liver Transplantation / immunology*
  • Liver Transplantation / pathology
  • Male
  • Prednisolone / therapeutic use
  • Stomach / immunology
  • Stomach / pathology
  • Time Factors


  • Autoantibodies
  • Immunosuppressive Agents
  • anti-liver kidney microsome antibody
  • Cyclosporine
  • Prednisolone
  • Cytochrome P-450 CYP2D6
  • Azathioprine