494
Articles Liver Transplantation Experience With 1 00 Cases JEAN-LUC SZPAKOWSKI, MD, Richmond; KEN COX, MD; PAUL NAKAZATO, MD; WALDO CONCEPCION, MD; BARRY LEVIN, MD; and CARLOS 0. ESQUIVEL, MD, PhD, San Francisco, California
Between March 1988 and November 1989, 100 liver transplants were performed on 90 patients at Pacific Presbyterian
(now California Pacific) Medical Center in San Francisco. The immunosuppressive regimen was a combination of prophylactic Minnesota antilymphocyte globulin, cyclosporine, and low-dose corticosteroids. Rejections were treated with OKT3, a monoclonal antibody, or corticosteroids. Of the 100 transplants, 32 were done on 30 children, 18 of whom weighed less than 10 kg and 9 of whom received livers that had been surgically reduced in size to fit the recipient. The overall patient survival at 2 years was 850/%. Of 100 liver transplants, treatment was given for 80 (80%) for at least 1 episode of rejection. At least 1 episode of serious infection occurred in 34 of the 60 adult patients and 25 of the 30 children. Of the entire group, 20/o had hepatic artery thrombosis, and 12% had biliary complications that necessitated reoperation. The quality of life has been good, with a follow-up from 1 to almost 3 years (mean=22 months). Comparing these data with those of other published series shows a decreased incidence of surgical complications and a lower rate of fungal and viral infections. We attribute this to the reduction of steroid dosage during convalescence without jeopardizing patient or graft survival. (Szpakowski JL, Cox K, Nakazato P, Concepcion W, Levin B, Esquivel CO: Liver transplantation-Experience with 100 cases. West J Med 1991 Nov; 155:494-499)
Hepatic transplantation is the treatment of choice for patients with irreversible acute and chronic liver disease.' Although survival statistics are excellent, the procedure is still associated with substantial morbidity and mortality from surgical complications, infection, and rejection.`24 The Liver Transplant Program at the California Pacific (formerly Pacific Presbyterian) Medical Center in San Francisco uses an immunosuppressive protocol combining Minnesota antilymphocyte globulin, cyclosporine, and low doses of corticosteroids in an attempt to decrease morbidity and mortality. We report, through medical records review, experience with our first 100 cases (90 patients). The procedure was done between March 1988 and November 1989, with follow-up from 12 to 34 months (mean = 22 months). Patients and Methods Patients who were considered to have irreversible renal failure had combined liver and kidney transplantation. Absolute contraindications for liver transplantation included seropositivity for the human immunodeficiency virus confirmed by Western blot testing or polymerase chain reaction, nonreconstructible anatomy (extensive thrombosis involving the portal, superior mesenteric, and splenic veins), extrahepatic cancer, and continued alcohol or intravenous drug abuse. Relative contraindications included congestive heart failure, severe coronary artery disease, chronic uncontrollable seizure disorder, and uncontrollable sepsis. Organ procurement was usually performed by our transplant team using an en bloc technique.5 All grafts were preserved with the University of Wisconsin preservation solution.6 The recipient operation was done as described in the literature.7 Venous bypass was used when recipients weighed more than 15 kg. Nine children received reducedsize livers8 that consisted of eight left lobes (segments II, III,
and IV), and one received a lateral segment (segments II and III). In adults, 79 % of the biliary reconstructions were carried out with an end-to-end choledochocholedochostomy and 21% with an end-to-side choledochojejunostomy to a Rouxen-Y anastomosis. The latter was done in all but one child, who had an end-to-end choledochocholedochostomy. Five patients had portosystemic shunts. Immunosuppression The initial immunosuppressive protocol involved three drugs. Cyclosporine, 2 to 3 mg per kg per day, was given intravenously as a continuous infusion, starting on the second or third postoperative day depending on renal function. It was given orally when digestive function returned, although there was usually an overlap of intravenous and oral administration to ensure therapeutic concentrations (between 300 and 500 mg per ml). A corticosteroid regimen was begun intraoperatively with an intravenous bolus of methylprednisolone sodium succinate, 14 mg per kg of body weight, followed by a maintenance dose of 0.3 mg per kg per day given intravenously and changed to prednisone at the same dose when oral intake was begun. At the beginning of the third week, this was reduced to 0.2 mg per kg per day. Minnesota antilymphocyte globulin, a polyclonal horse -y-globulin preparation, was given for the first seven to ten days, beginning at a dose of 5 mg per kg intravenously on the first day, 10 mg per kg on the second day, and 15 mg per kg on the third and following days until therapeutic levels of cyclosporine were reached (Figure 1). OKT3 was used as induction therapy in renal failure, in patients with positive crossmatches, and in transplants across the ABO groups.
Hepatic Dysfunction After transplantation, patients with hepatic dysfunction underwent thorough evaluations including radiologic stud-
From the Transplant Institute, California Pacific Medical Center, San Francisco, California. Dr Szpakowski is now with Kaiser Permanente, Richmond, California. Reprint requests to Carlos 0. Esquivel, MD, PhD, 2340 Clay St, #425, San Francisco, CA 94115.
THEH WESTERN JOURNAL OF MEDICINE
NOVEMBER 1991
155 *
*
5
495
Steroid Pulse V
200
72~ Prednisone ZK PO Cyclosporine 1-- IV Cyclosporine
.-E
-__ ALG i-i Cyclosporine Level
° 20
ng/ml 500
c0 -0
a) 210 cn -15 10
-E 15 E 10 __r
C
18 yr)
6 60 46.48 (22-67)
WMeanweight, kg' (rnge)
68(38-99)
listed in Table 2. Two patients underwent transplantation elsewhere and received secondary transplants at our institution. One was a child with hepatic artery thrombosis, and the other was an adult with recurrent fulminant hepatitis B. Table 3 shows the pretransplant biochemical variables of the patients according to the diagnostic indications for transplantation.
Rejection In adults, 54 of 68 grafts (79%) had at least one episode of hepatic dysfunction treated as rejection. In children, 81%, or 26 of 32 grafts, had rejection episodes. Two patients treated with OKT3 lost their grafts from chronic rejection at 6 and 24 months after transplantation. One of these patients was an adolescent who discontinued her medications. OKT3 was used in 28 of the 60 (47%) adults. In 10 of the patients, OKT3 was given as induction therapy and in 18 as treatment of rejection. Of 30 children, 13 (43%) were given OKT3, in 2 children as induction and in 11 as antirejection therapy. Five patients who had received OKT3 died, although only one had rejection as a contributory cause. Two died of recurrent hepatitis B, and two died of lymphoproliferative disease.
TABLE2.-IhdicationsforHepoticTransplantation Patients,
No.
cirrhosis : Cryptogenic La nnec cirrhosis ...................... .
................. ..
13 (22) 11 (18) 10 (15)
Primary Cbi i ....cirrsis .... .........: . .............. 6 (10) Chroni hepttiis B ~Autmune hepatitis..5 (8) Fulminant chpatitis I...... ......5........ (8)
Drug toxicity......I.........
S§clerosing cho1angis.. Hemochromatoiis
................
. .............. Wilsons-disease '..Budd-Chiari syndrome . ................... . : ............ ax,-Antitrypsin deficiencvy .. hepatitis (retransplant) Children (n=30)
Articles Liver Transplantation Experience With 1 00 Cases JEAN-LUC SZPAKOWSKI, MD, Richmond; KEN COX, MD; PAUL NAKAZATO, MD; WALDO CONCEPCION, MD; BARRY LEVIN, MD; and CARLOS 0. ESQUIVEL, MD, PhD, San Francisco, California
Between March 1988 and November 1989, 100 liver transplants were performed on 90 patients at Pacific Presbyterian
(now California Pacific) Medical Center in San Francisco. The immunosuppressive regimen was a combination of prophylactic Minnesota antilymphocyte globulin, cyclosporine, and low-dose corticosteroids. Rejections were treated with OKT3, a monoclonal antibody, or corticosteroids. Of the 100 transplants, 32 were done on 30 children, 18 of whom weighed less than 10 kg and 9 of whom received livers that had been surgically reduced in size to fit the recipient. The overall patient survival at 2 years was 850/%. Of 100 liver transplants, treatment was given for 80 (80%) for at least 1 episode of rejection. At least 1 episode of serious infection occurred in 34 of the 60 adult patients and 25 of the 30 children. Of the entire group, 20/o had hepatic artery thrombosis, and 12% had biliary complications that necessitated reoperation. The quality of life has been good, with a follow-up from 1 to almost 3 years (mean=22 months). Comparing these data with those of other published series shows a decreased incidence of surgical complications and a lower rate of fungal and viral infections. We attribute this to the reduction of steroid dosage during convalescence without jeopardizing patient or graft survival. (Szpakowski JL, Cox K, Nakazato P, Concepcion W, Levin B, Esquivel CO: Liver transplantation-Experience with 100 cases. West J Med 1991 Nov; 155:494-499)
Hepatic transplantation is the treatment of choice for patients with irreversible acute and chronic liver disease.' Although survival statistics are excellent, the procedure is still associated with substantial morbidity and mortality from surgical complications, infection, and rejection.`24 The Liver Transplant Program at the California Pacific (formerly Pacific Presbyterian) Medical Center in San Francisco uses an immunosuppressive protocol combining Minnesota antilymphocyte globulin, cyclosporine, and low doses of corticosteroids in an attempt to decrease morbidity and mortality. We report, through medical records review, experience with our first 100 cases (90 patients). The procedure was done between March 1988 and November 1989, with follow-up from 12 to 34 months (mean = 22 months). Patients and Methods Patients who were considered to have irreversible renal failure had combined liver and kidney transplantation. Absolute contraindications for liver transplantation included seropositivity for the human immunodeficiency virus confirmed by Western blot testing or polymerase chain reaction, nonreconstructible anatomy (extensive thrombosis involving the portal, superior mesenteric, and splenic veins), extrahepatic cancer, and continued alcohol or intravenous drug abuse. Relative contraindications included congestive heart failure, severe coronary artery disease, chronic uncontrollable seizure disorder, and uncontrollable sepsis. Organ procurement was usually performed by our transplant team using an en bloc technique.5 All grafts were preserved with the University of Wisconsin preservation solution.6 The recipient operation was done as described in the literature.7 Venous bypass was used when recipients weighed more than 15 kg. Nine children received reducedsize livers8 that consisted of eight left lobes (segments II, III,
and IV), and one received a lateral segment (segments II and III). In adults, 79 % of the biliary reconstructions were carried out with an end-to-end choledochocholedochostomy and 21% with an end-to-side choledochojejunostomy to a Rouxen-Y anastomosis. The latter was done in all but one child, who had an end-to-end choledochocholedochostomy. Five patients had portosystemic shunts. Immunosuppression The initial immunosuppressive protocol involved three drugs. Cyclosporine, 2 to 3 mg per kg per day, was given intravenously as a continuous infusion, starting on the second or third postoperative day depending on renal function. It was given orally when digestive function returned, although there was usually an overlap of intravenous and oral administration to ensure therapeutic concentrations (between 300 and 500 mg per ml). A corticosteroid regimen was begun intraoperatively with an intravenous bolus of methylprednisolone sodium succinate, 14 mg per kg of body weight, followed by a maintenance dose of 0.3 mg per kg per day given intravenously and changed to prednisone at the same dose when oral intake was begun. At the beginning of the third week, this was reduced to 0.2 mg per kg per day. Minnesota antilymphocyte globulin, a polyclonal horse -y-globulin preparation, was given for the first seven to ten days, beginning at a dose of 5 mg per kg intravenously on the first day, 10 mg per kg on the second day, and 15 mg per kg on the third and following days until therapeutic levels of cyclosporine were reached (Figure 1). OKT3 was used as induction therapy in renal failure, in patients with positive crossmatches, and in transplants across the ABO groups.
Hepatic Dysfunction After transplantation, patients with hepatic dysfunction underwent thorough evaluations including radiologic stud-
From the Transplant Institute, California Pacific Medical Center, San Francisco, California. Dr Szpakowski is now with Kaiser Permanente, Richmond, California. Reprint requests to Carlos 0. Esquivel, MD, PhD, 2340 Clay St, #425, San Francisco, CA 94115.
THEH WESTERN JOURNAL OF MEDICINE
NOVEMBER 1991
155 *
*
5
495
Steroid Pulse V
200
72~ Prednisone ZK PO Cyclosporine 1-- IV Cyclosporine
.-E
-__ ALG i-i Cyclosporine Level
° 20
ng/ml 500
c0 -0
a) 210 cn -15 10
-E 15 E 10 __r
C
18 yr)
6 60 46.48 (22-67)
WMeanweight, kg' (rnge)
68(38-99)
listed in Table 2. Two patients underwent transplantation elsewhere and received secondary transplants at our institution. One was a child with hepatic artery thrombosis, and the other was an adult with recurrent fulminant hepatitis B. Table 3 shows the pretransplant biochemical variables of the patients according to the diagnostic indications for transplantation.
Rejection In adults, 54 of 68 grafts (79%) had at least one episode of hepatic dysfunction treated as rejection. In children, 81%, or 26 of 32 grafts, had rejection episodes. Two patients treated with OKT3 lost their grafts from chronic rejection at 6 and 24 months after transplantation. One of these patients was an adolescent who discontinued her medications. OKT3 was used in 28 of the 60 (47%) adults. In 10 of the patients, OKT3 was given as induction therapy and in 18 as treatment of rejection. Of 30 children, 13 (43%) were given OKT3, in 2 children as induction and in 11 as antirejection therapy. Five patients who had received OKT3 died, although only one had rejection as a contributory cause. Two died of recurrent hepatitis B, and two died of lymphoproliferative disease.
TABLE2.-IhdicationsforHepoticTransplantation Patients,
No.
cirrhosis : Cryptogenic La nnec cirrhosis ...................... .
................. ..
13 (22) 11 (18) 10 (15)
Primary Cbi i ....cirrsis .... .........: . .............. 6 (10) Chroni hepttiis B ~Autmune hepatitis..5 (8) Fulminant chpatitis I...... ......5........ (8)
Drug toxicity......I.........
S§clerosing cho1angis.. Hemochromatoiis
................
. .............. Wilsons-disease '..Budd-Chiari syndrome . ................... . : ............ ax,-Antitrypsin deficiencvy .. hepatitis (retransplant) Children (n=30)
