Liver Transplantation with Use of Cyclosporin a and Prednisone

Abstract

The difficulties in consistently prolonging survival after orthotopic liver transplantation have been documented by us 1 and by Calne. 2 In this report we describe a new trial of orthotopic liver transplantation in 14 patients who were scheduled to be treated with cyclosporin A and prednisone. Two patients died during the operation. Ten (83 per cent) of the 12 patients who survived surgery and received the drugs are living after eight to 14½ months; another lived for a year, before dying of a recurrence of cholangiocarcinoma.Although longer follow-up periods and more case studies will be required to establish the safety and effectiveness of this form of therapy, the exceptionally encouraging early results seem attributable to the use of cyclosporin A in combination with low doses of steroids for immunosuppression. The first use of cyclosporin A in liver transplantation was reported by Calne et al. 3 MethodsFourteen patients (age range, eight to 41 years) were accepted for the pilot trial. Liver replacement was attempted between March 10 and September 28, 1980. Two patients who were scheduled to be treated with cyclosporin A plus prednisone died during operation. One bled to death from a laceration of the portal vein, and the other received a homograft too large to permit the abdomen to be closed. Thus only 12 patients were treated with immunosuppression. TransplantationThe general techniques used in these operations have been previously described. 1,4 Seven of the 14 livers were removed during operations in cities other than Denver (75 to 2000 miles [120 to 3200 km] away). All 14 livers were preserved with Collins' solution, as described by Benichou et al. 5 Ischemia lasted from 1½ to 10½ hours. Biliary-tract reconstruction was performed through duct-to-duct, gallbladder-to-jejunal-Roux-limb, and common-duct-toRoux-limb anastomosis, in that order of frequency. Selection of Recipients and DonorsOf the 12 patients who survived the operation, three had chronic aggressive hepatitis and three had the Budd-Chiari syndrome. The following diseases were present in one patient each: primary biliary cirrhosis, secondary biliary cirrhosis, sclerosing cholangitis, hepatoma, Byler's NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript disease, and intrahepatic atresia. Of the two patients who died during operation, one had sclerosing cholangitis and the other had secondary biliary cirrhosis (caused by a gunshot wound to the hepatic hilum).Each donor was blood-group compatible with each respective recipient. There were no positive T-cell or B-cell cytotoxic cross matches at warm temperatures. In the 12 surviving patients, mismatches at the A and B loci averaged 3.3±0.7 (S.D.) and matches averaged 0.6±0.5. The number of matching DR loci ranged from 0 to 1 (mean, 0.4). ImmunosuppressionCyclosporin A treatment was started on the day of operation (17.5 mg per kilogram of body weight per day, given intramuscularly or by mouth). After six to eight weeks the doses were reduced to 10 mg per kilogram per day or le...

Orthotopic Liver Transplantation for Alcoholic Cirrhosis

“…Urgency of need was defined with a six-tier stratification that was originally developed in 1982 and was recently applied nationally by the United Network for Organ Sharing as one of the factors for the equitable allocation of extrarenal organs. 3 The six urgency classifications are defined as follows: (1) working or in school; (2) The patients were treated at the University of Colorado Medical Center, Denver.…”

“…1 To help judge the merit of such negative attitudes, we have examined the fate of 56 alcoholic recipients of liver transplants treated between 1963 and July 1987, with an emphasis on patients treated after the introduction of cyclosporine-steroid therapy in 1979. 2 …”

The Saga of Liver Replacement, with Particular Reference to the Reciprocal Influence of Liver and Kidney Transplantation (1955–1967)

“…Yet, the ultimate prize of tolerance was achieved less frequently than before, and only when liver transplantation was carried out during three time periods. The first two intervals were 1979-1980 and 1989-1990, just after cyclosporine 96 and tacrolimus,95,97 respectively, were introduced clinically as monotherapy, adding prednisone only to treat rejection, When prophylactic high doses of prednisone and other agents were added at the time of operation in an effort to further reduce the threat of acute rejection, drug-free tolerance was no longer seen. The third cluster of tolerant patients was produced at the turn of the century in Kyoto, Japan, where many pediatric recipients of partial livers from parental donors were successfully weaned from a steroid-sparing tacrolimus-based regimen of immunosuppression 98 similar to that originally used in [1989][1990].…”

Tacrolimus (FK506) and the pharmaceutical/academic/regulatory gauntlet

“…8 The first came in 1980 with the advent of cyclosporine, 8,24 and the second followed the introduction of tacrolimus. 11,25 A small increment temporally associated with the availability of the University of Wisconsin preservation solution in 1987 26,27 was dependent on the delayed rescue with tacrolimus of patients ailing on cyclosporin from the immediately preceding era.…”