Immunopathogenesis of hepatitis B virus recurrence after liver transplantation.
OBJECTIVE
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.
Marinos
G
G
Institute of Liver Studies, Department of Immunology, King's College School of Medicine and Dentistry, London, England.
Rossol
S
S
Carucci
P
P
Wong
P Y
PY
Donaldson
P
P
Hussain
M J
MJ
Vergani
D
D
Portmann
B C
BC
Williams
R
R
Naoumov
N V
NV
D000328:Adult; D001706:Biopsy; D016207:Cytokines / Q000097:blood; D005260:Female; D006680:HLA Antigens / Q000032:analysis; D006509:Hepatitis B / Q000209:etiology*; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D008099:Liver / Q000737:chemistry / Q000473:pathology; D016031:Liver Transplantation / Q000009:adverse effects* / Q000473:pathology; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D018124:Receptors, Tumor Necrosis Factor / Q000097:blood; D012008:Recurrence; D018417:Th1 Cells / Q000276:immunology / Q000821:virology; D018418:Th2 Cells / Q000276:immunology / Q000821:virology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D016207:Cytokines; D006680:HLA Antigens; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma