Long-term use of cyclosporin in liver grafting

The clinical course of 29 liver graft recipients in the Cambridge/King's College Hospital series who have received cyclosporin A (CyA) for up to five years (median 40 months) was analysed with particular reference to the immunosuppressive effectiveness and adverse effects of the drug. Eight patients had been maintained on prednisolone and azathioprine for two to six years before treatment was changed to cyclosporin A and the remainder were started on cyclosporin A after operation. Results in both groups over a one to five year study period are similar, and showed that cyclosporin A was effective in maintaining adequate immunosuppression, allowing complete withdrawal of prednisolone in 16 patients. Episodes of rejection were observed in only three patients and in two of these it was of the chronic 'vanishing bile duct' variety. Some evidence of nephrotoxicity (serum creatinine greater than 150 mumol/l) occurred in 72 per cent (21 of 29 patients) but it was necessary to discontinue treatment in only two. Hypertension, occasionally of sudden onset, was found in nine patients and led to the withdrawal of the drug in two. Additional hypotensive drug treatment was required in five. In one other patient cyclosporin A was discontinued on account of severe headaches. Cyclosporin A was withdrawn in two further patients. Withdrawal led to considerable risk of acute rejection and increased doses of corticosteroids as well as substitution of azathioprine were required at that time.