Immunosuppression and other nonsurgical factors in the improved results of liver transplantation

Abstract

During the last 5 years, liver transplantation has become a service as opposed to an experimental operation. The most important factor in making this possible has been the introduction of cyclosporine-steroid therapy. At the same time, liver transplantation has been made more practical by improvements in diagnosing and managing other causes of postoperative hepatic dysfunction. Tissue typing and matching have played no role in improving the results of liver transplantation. With the demonstration that performed antibody states are irrelevant, even avoidance of positive cross-matches caused by cytotoxic antibodies and observance of ABO blood group barriers have become unnecessary if the recipient's needs are great. With the exceptions of malignancy and cirrhosis, the nature of the underlying hepatic disease has not profoundly influenced the results. Retransplantation has played an important role in improving survival, although the costs of retransplantation have been extremely high.

Figures

FIG. 1. Results obtained over a 16-year period using the conventional immunosuppression regimens without cyclosporine, as shown in Table 1

Note the failure to improve the results despite the acquisition of considerable technical experience.

FIG. 2. Course of a recipient of a kidney graft who developed inexorable renal rejection despite good blood levels of cyclosporine and despite a second burst of high-dose steroid therapy

The rejection was immediately reversed with OKT3 therapy and with good function for the ensuing 8 months. Note the prompt reduction in circulating T-lymphocytes.

FIG. 3. Increasing numbers of liver transplantations at the University of Pittsburgh between 1981 and 1984

Note the significant number of retransplantations.

FIG. 4. The use of cyclosporine and steroids

Note that the cyclosporine initially is given intravenously (IV) and that the IV therapy is continued long after the drug is begun orally. The switch from double-route cyclosporine therapy to the oral route alone is carefully monitored with cyclosporine blood levels. Note the seeming increase in enteral absorption after clamping of the T-tube, the insistence on maintaining high blood levels of cyclosporine despite obvious low-grade nephrotoxocity, and the intensification of steroid therapy with either a cycle or intermittent bolus administration with suspicion of rejection. Large arrows: methylprednisolone sodium succinate; small arrows: hydrocortisone sodium succinate. (Reproduced with permission from Starzl et al.42)

FIG. 5

Marked improvement in results of liver transplantation after the introduction of cyclosporine-steroid therapy in ealry 1980.

FIG. 6

Results with adult versus pediatric liver transplantation under conventional immunosuppression between 1963 and early 1980.

FIG. 7

Comparison of results in adult and pediatric recipients during the cyclosporine era of 1980 to 1984.

FIG. 8

Percentages of liver transplantations in pediatric versus adult recipients at the University of Pittsburgh from 1981 through most of 1984.

FIG. 9

Survival of adult liver recipients in the precyclosporine versus the cyclosporine eras.

FIG. 10. Survival of pediatric patients in the precyclosporine versus the cyclosporine eras

Notice the remarkably high survival of children treated with cyclosporine-steroids during the first postoperative year as well as the fact that subsequent losses were extremely uncommon.

FIG. 11

The lack of influence of the underlying disease in adults treated for primary biliary cirrhosis, sclerosing cholangitis, and inborn errors of metabolism.

FIG. 12. Life survival curves of patients with cirrhosis and primary hepatic malignancy

Note the very high survival of patients with malignant disease during the first half year (856), but with a steady decline thereafter, which was due primarily to the development of metastases.

FIG. 13

Lack of influence of underlying disease on the survival of children undergoing liver transplantation.