Immunopathogenesis of hepatitis B virus recurrence after liver transplantation

Transplantation. 2000 Feb 27;69(4):559-68. doi: 10.1097/00007890-200002270-00017.


Background and aims: Hepatitis B virus (HBV) recurrence after orthotopic liver transplantation is associated with inflammatory graft changes, despite immunosuppression and donor/recipient HLA mismatch. We investigated whether immune mechanisms are involved in the pathogenesis of hepatitis B after liver transplantation.

Methods: The virus-specific T helper (Th) cell response, activation of Th1/Th2 subpopulations, donor/recipient HLA, and expression of tumor necrosis factor (TNF)-alpha/TNF receptors were determined in 28 patients who underwent transplantation for HBV-related cirrhosis (17 with HBV recurrence and 11 without recurrence) in comparison to 30 nontransplant patients with chronic hepatitis B.

Results: Orthotopic liver transplantation recipients with HBV recurrence showed significant hepatitis B core antigen-specific T-cell proliferation, comparable to nontransplant patients, which was not present in transplant recipients without recurrence. In addition, hepatic and serum interleukin (IL)-2, interferon-gamma, and TNF-alpha were enhanced, without changes in IL-4 and IL-10. Phenotypically, hepatic infiltrates in allografts with HBV recurrence were comprised of CD4+ lymphocytes and macrophages with a correlation between interferon-gamma- and TNF-alpha-producing cells and the degree of necroinflammatory activity. There was a marked up-regulation of both TNF-alpha receptors, significantly greater than in nontransplant patients.

Conclusions: These findings suggest that despite immunosuppression, HLA class I-independent immune mechanisms have a significant pathogenic role in liver damage associated with HBV recurrence after liver transplantation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Biopsy
  • Cytokines / blood
  • Female
  • HLA Antigens / analysis
  • Hepatitis B / etiology*
  • Humans
  • Interferon-gamma / biosynthesis
  • Liver / chemistry
  • Liver / pathology
  • Liver Transplantation / adverse effects*
  • Liver Transplantation / pathology
  • Lymphocyte Activation
  • Male
  • Middle Aged
  • Receptors, Tumor Necrosis Factor / blood
  • Recurrence
  • Th1 Cells / immunology
  • Th1 Cells / virology
  • Th2 Cells / immunology
  • Th2 Cells / virology
  • Tumor Necrosis Factor-alpha / biosynthesis


  • Cytokines
  • HLA Antigens
  • Receptors, Tumor Necrosis Factor
  • Tumor Necrosis Factor-alpha
  • Interferon-gamma