Immunosuppression strategies after liver transplantation: a single centre experience in 57 liver transplant recipients.

CONTEXT: The art of administering immunosuppression lies in the ability to achieve a delicate balance between rejection and infection, thus maximizing patient survival and minimizing morbidity. AIMS: To analyze the effect of immunosuppression strategies following liver transplant on the incidence of acute rejection, bile leak, renal dysfunction and posttransplant graft unrelated infection. SETTINGS AND DESIGN: A retrospective analysis of immunosuppression regimens in 57 liver transplant recipients between Jan 1998 to July 2004 at a single institution. METHODS AND MATERIAL: For the purpose of study, the patients were divided into two groups: A - Cyclosporine based therapy (n=37), and B - Tacrolimus based therapy (n=20). In addition, both groups received Azathioprine or Mycophenolate mofetil with steroids. There were two subgroups in each Group A and B: Group C - Received induction using IL2Rab (n=5), and D - Where Sirolimus was used instead of Mycophenolate mofetil (N=7). The subgroups were equally distributed among the basic groups. The regimen was started based on one of the standard protocols but changes were made according to the clinical status of each patient. STATISTICAL ANALYSIS USED: The statistical analysis was done using Chi square test on SPSS12. RESULTS: A lower incidence of rejection was observed in Tacrolimus group compared to Cyclosporine group. There was an unacceptably high incidence of bile leak in patients where Sirolimus was used as an adjunct. IL2Rab enabled us to maintain a lower trough level of Tacrolimus for maintenance and enabled us to discontinue steroids earlier. CONCLUSIONS: Based on this study we dropped Sirolimus from our immunosuppression protocol and the encouraging results obtained with tacrolimus based therapy have supported its use as standard therapy in our immunosuppression regimens.

Liver transplantation in the developing world.

Liver transplantation is an accepted therapy for acute and chronic liver failure. Advances in preoperative and postoperative management and surgical techniques have extended the indications and improved results. Most international centres report one year actual survival rates of between 58-90% and 5-8 years survival of 75-80%. These developments, however, have been limited largely to the West. While the need for liver transplantation is well recognised in the developing world, liver transplantation has only recently been performed successfully in India. This article examines the challenges of liver transplantation in the developing world.

T-cell anergy: a consequence of interaction between T cells and allogeneic rat renal epithelial cells.

In order to study the immunogenicity of parenchymal cells within an allograft, renal tubular cells were propagated from both PVG and DA strain rats. These cells were induced to express class II major histocompatibility (MHC) antigens by stimulation for 4 days with interferon-gamma (IFN-gamma). It was found that resting lymphoid cells derived from Lewis rats responded vigorously after stimulation with irradiated splenic cells from PVG rats. However, stimulation with renal cells from PVG rats did not result in interleukin (IL-2) production or lymphoproliferation. Furthermore, lymphocytes from this mixture failed to respond to secondary stimulation by PVG splenic cells; lymphocytes primed by mixture with DA renal cells responded normally to secondary stimulation by PVG splenic cells. These results indicate that renal epithelial cells can specifically anergise allogeneic lymphocytes.

Experimental renal transplantation: IgG antibodies which bind to graft tubular epithelial cells cannot be detected in the serum of recipient rats after pre-operative transfusion of donor blood.

Transfusion of donor blood 7 days prior to renal transplantation between certain rat strain combinations can delay subsequent graft rejection. The mechanism responsible for this increased graft tolerance remains largely unclear. In this paper it is demonstrated that IgG antibodies with affinity for cultured donor renal epithelial cells develop in the plasma of recipient PVG rats within 7 days of transplantation of a DA rat kidney. These IgG antibodies are not specific for kidney cell-restricted antigens as the activity can be completely absorbed using cells which express donor class-I MHC antigens. However, the IgG may contribute to the acute rejection of graft cells by activating antibody-dependent cell-mediated cytolytic (ADCC) mechanisms. Transfusion of donor blood 7 days prior to renal transplantation between DA and PVG rats prevented the development of IgG antibodies which bind to resting or cytokine-activated donor renal epithelial cells. Serum taken 7 days after the transplantation of animals which had been previously transfused with donor blood was not able to activate ADCC mechanisms of donor cells. The donor blood transfusion-mediated abrogation of IgG binding to graft cells may delay the onset of graft rejection by preventing antibody-dependent graft cell lysis.

Interaction between T lymphocytes and kidney epithelial cells during renal allograft rejection.

Cultured human renal epithelial cells were treated with the cytokines IFN-gamma and TNF-alpha and alteration in expression and function of markers including Classes I and II MHC antigens and the adhesion molecules LFA-3 and ICAM-1 was examined. It was found that a mixture of IFN-gamma and TNF-alpha induced Class II MHC antigens, up-regulated expression of Class I, LFA-3 and ICAM-1 molecules and enhanced binding of 51Cr-labeled mononuclear immune cells. However, lymphocytes failed to proliferate in response to allo-stimulation by renal epithelial cells. Lymphocytes recovered after four days in mixed culture with allogeneic renal cells were purified and re-stimulated with irradiated spleen cells for five days prior to measurement of proliferation. These lymphocytes failed to proliferate if the spleen cells were syngeneic with the renal cells used in the primary stimulation. However, if the renal cells were from a third-party donor the lymphocytes showed a normal proliferative response to the allogeneic spleen cells. It has been demonstrated that cytokine-stimulated renal epithelial cells bind, but fail to initiate proliferation of, resting allogenic lymphocytes and that activated renal cells can specifically anergise potentially graft damaging allospecific T lymphocytes.

Role of duplex imaging and fine needle aspiration cytology of renal allografts in monitoring response to anti-rejection therapy.

The role of duplex imaging and fine-needle aspiration cytology (FNAC) in monitoring the response to anti-rejection therapy was investigated in 14 of the 22 rejection episodes which occurred in 30 renal allografts recipients. In 9 of these 14 episodes of rejection, with good resolution, both resistive (RI) and pulsatility (PI) indices decreased by significant proportions (p less than 0.05). The FNAC scores also fell significantly with anti-rejection therapy. In 5 other episodes of rejection where the graft continued to deteriorate there was no significant fall of RI and PI (p greater than or equal to 0.2). In a small group of patients, both FNAC and Doppler predicted rejection. In conclusion, both duplex imaging and FNAC have a role in selection and optimal modulation of drugs in the treatment of acute renal allograft rejection.