This dissertation, "Hepatitis B Virus: Specific Immune Response After Liver Transplantation for Chronic Hepatitis B" by Ying, Luo, 羅英, was obtained from The University of Hong Kong (Pokfulam, Hong Kong) and is being sold pursuant to Creative Commons: Attribution 3.0 Hong Kong License. The content of this dissertation has not been altered in any way. We have altered the formatting in order to facilitate the ease of printing and reading of the dissertation. All rights not granted by the above license are retained by the author. Abstract: Abstract of thesis entitled Hepatitis B Virus - Specific Immune Response after Liver Transplantation for Chronic Hepatitis B Submitted by Ying LUO For the degree of Doctor of Philosophy at the University of Hong Kong in October 2006 In patients with chronic hepatitis B virus (HBV) infection, HBV-specific immune response may be modified after liver transplantation due to the removal of major reservoir of virus in explanted liver, ongoing antiviral treatment and immunosuppression, and potentially adoptive immunity transfer through allografts. In this study, we aim to characterize the kinetics of HBV-specific immune response after liver transplantation for chronic HBV infection using lamivudine monoprophylaxis, and to elucidate further the adoptive transfer of HBV immunity through liver transplantation. Firstly, the resident lymphocytes in 41 human liver grafts were analyzed with immunohistochemistry, flow cytometry and enzyme-linked immunospot assays. A considerable number of lymphocytes with a distinct phenotype were detectable in these liver grafts after perfusion with preservative solution. HBV-specific T and B cells were identified in 59% (19/32) and 28% (9/32), respectively, of grafts from HBV-immune donors. The presence of various HBV-specific lymphocytes was significantly associated with each other and with the spontaneous production of antibody against hepatitis B surface antigen (anti-HBs) in recipients after transplantation. Secondly, a cross-sectional study was carried out to assess the HBV-specific CD4+ T cell immune response in 40 patients without HBV recurrence at 1 year (n=29) or at 5 years (n=11) after liver transplantation for chronic hepatitis B, and in 12 with recurrent HBV infection. Compared to pre-transplant patients with chronic HBV infection, T cell proliferation and interferon-γ-secreting T cell responses to HBV antigens were significantly lower, and were not detectable in most recipients without HBV recurrence. The T cell proliferation responses to mitogen and recall antigen, however, were maintained. In contrast, those with HBV recurrence showed significant T cell responses to HBV that were significantly associated with the viral load in serum. Finally, the serial changes of HBV-specific humoral and cellular immune response was prospectively studied for 1 year in 60 patients who underwent liver transplantation for HBV-related liver disease using lamivudine monoprophylaxis. After an initial significant decline following transplantation, T cell proliferation responses to mitogen and recall antigen increased progressively and exceeded the pre-transplant levels at 1 year after transplantation. The HBV-specific T cell responses, however, showed only a transient restoration with a peak between 1 and 3 months after transplantation. The recipients' post-transplant T cell responses to HBV were independently associated with the donors' and recipients' pre-transplant T cell reactivity against HBV. In addition, 23 of 60 (38%) recipients spontaneously developed anti-HBs in serum after transplantation, and the anti-HBs production was also significantly associated with both donor's and recipient's pre-transplant T cell reactivity to HBV. In conclusion, the presence of donor-derived HBV-specific lymphocytes in grafts may account for the adoptive transfer of HBV immunity through liver transplantation. The