**8.2 PTLD**

Posttransplant lymphoproliferative disease (PTLD) is a growing concern in transplanted patients. Most cases of PTLD are of B-cell origin and are linked to EBV infections. Patients present with constitutional symptoms such as night sweats, fever, and weight loss. An acute rise in creatinine levels, similar to what occurs during acute allograft rejection, may also be seen. Risk factors for PTLD include primary EBV infection; the use of cyclosporine, tacrolimus, and MMF; and exposure to anti-thymocyte globulin (ATG) or OKT3. Treatment options include reduction or discontinuation of immunosuppression with an increase in prednisone to reduce rejection risk.

The long-term survival of liver transplant recipients requires lifelong treatment with immunosuppressive drugs. Despite the use of multiple agents in smaller doses, significant toxicities that are either directly or indirectly related to the immunosuppressive therapy can occur[27]. The primary long-term effects of corticosteroids include growth inhibition, Cushing's syndrome, osteoporosis, avascular femoral head necrosis, cataracts, glaucoma, cardiovascular disease and gastritis-peptic ulcer disease. The long-term effects of azathioprine include hepatitis, pancreatitis and red-cell aplasia. For cyclosporine, the longterm effects include hypercholesterolemia, arteriosclerosis, hypertension and nephrotoxicity. The long-term effects of tacrolimus may include hypertension and nephrotoxicity; however, it is too early to determine what other side effects may develop over time for this drug.

In summary, significant progress has been made in developing effective immunosuppressive protocols. These protocols rely on combination therapy using multiple drugs at low dosage to prevent rejection, treat established rejection episodes and minimize both the short-term toxicities and the long-term complications associated with immunosuppressive therapy.
