Fetal-tissue implants appear to offer long-term clinical benefit to some patients with advanced Parkinson's disease.
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...
plantation are due to cardiovascular disease and another 40% We prospectively withdrew prednisone in 28 adult paare due to infection. 4 tients who had stable graft function more than 2 yearsWe previously have observed a high prevalence of cardioafter orthotopic liver transplantation (OLTx) and had vascular risk factors in patients late after liver transplantabeen on 5 mg/d prednisone for at least 6 months. Prednition. 4 One year after successful liver transplantation in our sone was decreased from 5 mg/d to 2.5 mg/d for 1 month patient population, the incidence of diabetes was 13% and then stopped completely. Cyclosporine monotherapy the incidence of hypertension was 69.1%. In addition, 31% of was maintained at a level of approximately 200 ng/mL our patients had serum cholesterol levels ú 240 ng/mL at 1 (TDX). Nineteen patients had prednisone withdrawn year. Tapering of prednisone from 10 mg/d to 5 mg/d dewithout complications. Four (14.2%) had modest elevacreased these metabolic complications in some patients and tions in liver function tests (two biopsy proven mild resignificantly decreased serum cholesterol levels. jections and two were not biopsied). These four wereIn this study, we further explore the role of prednisone in treated with methylprednisolone boluses and then withthe development of metabolic complications after liver transdrawal of steroids again. Prednisone was restarted in plantation. We prospectively withdrew prednisone in liver five patients because of generalized fatigue and body transplantation recipients who had survived at least 2 years aches (n Å 4) and colitis (n Å 1). Steroids later were after transplantation to determine if the metabolic complicasuccessfully withdrawn in two of these patients. After tions such as diabetes, hypertension, and hypercholesterolprednisone withdrawal, three of five insulin-dependent emia could be decreased. diabetic patients were able to discontinue insulin therapy and their glycosylated hemoglobin levels improved. ied. In this group during the study period, no diabetic also were excluded because they do not receive maintenance prednibecame normoglycemic, no patient decreased their anti-sone immunosuppression at our center. No children were included hypertensive medicine, and the mean serum cholesterol in this study. levels did not change significantly. We conclude that At the time of the study, 52 patients at our institution were at prednisone withdrawal using cyclosporine monother-least 2 years after OLTx and on 5 mg/d of prednisone. Twelve patients were excluded from this initial study because they had a hisapy late after liver transplantation does not lead to graft Two patients refused participation. Finally, 28 patients were included in the study. No patient was dropped from the study after enrollment. The 24 patients not included in the steroid withdrawal As more patients enjoy long-term survival after liver trans-study were maintained on 5 mg/d prednisone throughout the study period and continued to be followed with monthly laboratory values. planta...
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