Liver transplantation graft rejection

Organ transplants The safety and efficacy of peginterferon alfa-2b alone or in combination with ribavirin capsules for the treatment of hepatitis C in patients who have received liver or other organ transplants have not been studied. Preliminary data indicate that interferon alpha therapy may be associated with an increased rate of kidney graft rejection. Liver graft rejection also has been reported, but a causal... 

Muromonab is a mouse monoclonal antibody against the CD3 receptor of T-lymphocytes. Its activity is based on inhibition of interactions between antigen-presenting cells and T-cells. By preventing antigen presentation it suppresses T-cell activation and proliferation. The indication for muromonab is the treatment of acute graft rejection after kidney, liver and hart transplantations. Its adverse effects consist of those symptoms that are initiated by the release of cytokines and lymphokines as a result of the reaction of muromonab with CD3 positive T-lymphocytes. These symptoms may vary from a mild flu-like syndrome to serious cardiac, pulmonale and neurological reactions. 

The drugs like azathioprine and cyclosporine A are used chiefly to prevent transplant rejection and in the treatment of autoimmune diseases. They are used to prevent graft rejection after kidney, liver, lung, pancreas transplant or bone marrow transplantation. 

Prophylaxis of graft rejection in kidney, liver, and heart allogeneic transplantation... 

Tacrolimus is given orally (twice-daily dose regimen) or as an injection. A modified release (MR) oral dosage form of tacrolimus has been developed for administration once a day to overcome noncompliance, which is the major problem in acute graft rejection in solid transplant recipients. Tacrolimus is not completely absorbed by the GI tract and its rate of absorption could vary. It binds to plasma protein at a rate of 75-99% with a half-life of approximately 12 h and is predominantly metabolized in liver by CYP3A. Some of its metabolites have immunosuppressive activity. Most of the tacrolimus is excreted in feces, and a negligible amount (< 1%) is excreted in urine without undergoing any metabolism. 

Muromonoab-CD3 is used for the treatment of acute organ transplant rejection. It is effective in preventing graft rejection after kidney, heart or liver transplantation. Muromonoab-CD3 is effective in patients who after acute cardiac or liver allograft rejection do not respond to steroid therapy. It is administered intravenously and with a dose of 5 mg/day, a general concentration range of 400-1500 ng/ml can be achieved. A serum concentration of 600-1150 ng/ml in renal transplant patients produces desirable immunosuppressive effects. The levels of CD3 expression, their production and antibodies to the drug determine its rate of clearance. In the absence of antibodies to muromonoab-CD3, its half-life is about 18 h. 

There are only a few reports of hyperacute rejection after liver transplantation. This may be due to the ability of the Kupffer cells to remove cytotoxic antibodies formed against the graft because of their reticuloendothelial function. Acute rejection is the more common form of rejection, which is manifested within 7-10 days after liver transplantation and exhibits symptoms of fever, malaise, pain, tachycardia and hepatomegaly. Mental disorientation in patients has also been reported during acute rejection. Liver biopsy is performed to confirm acute rejection that is generally mild in nature, and lymphocytic infiltration is observed in the portal tracts under the endothelium of the sinusoids. 

Bartlett, A.S., Ramadas, R., Furness, S., Gane, E., McCall, J.L. The natural history of acute histologic rejection without biochemical graft dysfunction in orthotopic liver transplantation A systematic review. Liver Transplant. 2002 8 1147—1153... 

In a randomized study, 14 patients with liver transplants were given calcineurin inhibitors and 14 were given mycophenolate mofetil monotherapy (22). Those who were given mycophenolate had reversible episodes of acute graft rejection and there were no such episodes in those who were given calcineurin inhibitors. 

There are numerous case reports where patients on a calcineurin inhibitor, such as cyclosporine or tacrolimus, began taking St. John s wort and developed significant reductions in plasma concentrations of the drugs (74-81). Both cyclosporine and tacrolimus are metabolized by the CYP3A4 enzyme system, and cyclosporine is also a substrate of Pgp (74,81). There are reports of acute graft rejections caused by low cyclosporine or tacrolimus serum concentrations in heart, liver, and kidney transplant recipients who were taking St. John s wort (75,76). 

Hyperacute rejection rarely occurs in patients receiving a liver transplant. The liver s special status for transplantation is not fully understood, but the local release of cytokines may alter the immunologic reaction taking place in the liver. Early graft dysfunction is treated with supportive care and retransplantation if possible. 

As in the case of heart transplantation, retrospective HLA matching of liver donors and recipients shows that well-matched grafts are generally associated with a lower risk of rejection but not necessarily with improved graft survival. A definitive evaluation of the benefits, if any, of HLA matching in liver transplantation will require substantially more data than are available at present. 

Results of a randomized comparative study in pediatric liver transplantation between tacrolimus and cyclosporin showed equal patient survival (80% vs. 81%), graft survival (70% vs. 71%), and retransplantation rate (17% vs. 19%) at 1 year after transplantation. Of note, however, was a trend favoring tacrolimus in the prevention of acute rejection (52% vs. 79%) [52]. An additional benefit of tacrolimus in children is its steroid-sparing effect allowing for them to achieve more normal growth. In addition, the lack of gingival hyperplasia and hirsutism has made tacrolimus particularly valuable in the treatment of children undergoing liver transplantation. 

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