New approaches in the use of cyclosporine: with particular reference to the liver

Abstract

Liver transplantation in the highly practical form that exists today has been made possible by multiple agent immunosuppression of which the most important component is CsA. Present day practices of immunosuppression are certain to be changed and probably in the near future in order to increase the effectiveness of therapy and to reduce the nephrotoxicity and other side-effects that until now have inhibited further applications. The introduction of new drugs such as FK 506, some of which are clearly synergistic with CsA, could ameliorate past problems with drug toxicity. With such improvements, and possibly even with more clever use of therapy that already is available, wider and more complex use of liver transplantation will be possible.

Fig 1

Actuarial survival rates of 1,000 patients treated with CsA/steroid therapy compared with surivial of 170 patients treated with the “conventional” therapy used before 1980.

Fig 2

Liver transplantation in adults. Change in pattern of age distribution with recent increased numbers of older recipients. Note that the data for 1986 was for only the first nine months.

Fig 3

Propagation of activated lymphocytes from human biopsies with interleukin.

Fig 4

Lymphocyte culture technique in which human lymphocytes obtained from biopsies and cultured are exposed to donor cells. Clonal expansion results.

Fig 5

Prevention or inhibition of clonal expansion in primed human lymphocyte cultures by addition of CsA or other drugs.

Fig 6

Development of CsA-resistant clones in liver or heart biopsies that were undergoing clinical rejection.

Fig 7

Disappearance of “rogue” clones by the addition of the experimental drug FK 506.