Indications for liver transplantation in the cyclosporine era

One hundred seventy orthotopic liver transplants were performed under conventional immunosuppression with azathioprine and steroids with 1- and 5-year survivals of 32.9% and 20.0%, respectively. Since the introduction of cyclosporine-prednisone therapy in March 1980, 313 primary orthotopic liver transplants have been performed. Actuarial survivals at 1 and 5 years have improved to 69.7% and 62.8%, respectively. Biliary atresia is now the most common indication for liver replacement. In adults, primary biliary cirrhosis and sclerosing cholangitis have become more common indications for transplantation, and alcoholic cirrhosis and primary liver malignancy as indications have declined. Early enthusiasm for liver transplantation in patients with hepatic cancer has been tempered by the finding that recurrence is both common and rapid. An increasing number of patients with inborn errors of metabolism originating in the liver are receiving transplants, including patients with Wilson's disease, tyrosinemia, alpha-1-antitrypsin deficiency, glycogen storage disease, familial hypercholesterolemia, and hemochromatosis. Survival in this group of patients has been excellent (74.4% at 1 and 5 years). A hemophiliac who received a transplant for postnecrotic cirrhosis has survived and may have been cured of his hemophilia. About 20% of patients require retransplantation for rejection, technical failure, or primary graft failure. Only 4 of the patients receiving retransplants under conventional immunosuppression survived beyond 6 months, and all died within 14 months of retransplantation. Sixty-eight patients have received retransplants under cyclosporine-prednisone. Thirty-one patients are surviving, all for at least 1 year. Six of the 12 patients requiring a third transplant are alive 2 to 3 years after the primary operation. An aggressive approach to retransplantation in the patient with a failed graft is justified

Cyclosporine-Steroid Combination Therapy in 84 Cadaveric Renal Transplants

Sixty-three primary and 21 retransplant cadaver kidney allografts were placed in 77 patients over a one-year period with three- to six-month follow-up. Eight primary grafts (12.7%) and six retransplants (28.6%) were lost to rejection. Patient mortality was 3.9%. There were no grafts lost and no deaths due to opportunistic infections. Renal function at 6 months after transplantation was similar in all primary transplant recipients regardless of risk factors, including advanced age, diabetes, or the need for postoperative dialysis. © 1985, National Kidney Foundation, Inc.. All rights reserved

Liver transplantation for biliary atresia

Orthotopic liver transplantation was performed 15 months to 20 years ago in 126 recipients, all of whom were under 18 years of age. Eighty-six of these pediatric recipients were treated before 1980 with azathioprine (or eyclophosphamide) and prednisone, to which antilymphocyte globulin (ALG) usually was added. One-year patient survival was 40%. In the last 40 cases, the new drug cyclosporine has been given with low doses of steroids. The one-year patient survival increased to 65%. Both in the pre-cyclosporine era and more recently, the survival of patients with biliary atresia has been lower than in the next largest category of patients, namely, those with liver-based inborn metabolic errors. The difficulty of operation in patients with biliary atresia has been greater than in recipients with other diagnoses, partly because of previous operations such as portoenterostomy (Kasai procedure). Hepatic portoenterostomy, worthwhile as it is, has posed technical difficulties for eventual liver transplantation, particularly when complicated Roux limb techniques or venting procedures have been applied. In our total experience the longest survival after liver replacement in a child whose original diagnosis was biliary atresia is 132/3 years. © 1984 Société Internationale de Chirurgie

CONSENSUS CONFERENCE REPORT ON LIVER* TRANSPLANTATION.

Liver transplantation has been developed to the point of a service operation, the exploitation of which depends upon the establishment of multiple regional centers. The increased use of this procedure will permit the delivery of optimum health care to victims of end stage liver disease

Choosing a pediatric recipient for orthotopic liver transplantation

Between March 3, 1981, and June 1, 1984, 216 children were evaluated for orthotopic liver transplantation. Of the 216 patients, 117 (55%) had recelved at least one liver transplant by June 1, 1985. Fifty-five (25%) died before transplantation. The 117 patients who received transplants were grouped according to severity of disease and degree of general decompensation at the time of transplantation. The severity of a patient's medical condition with the possible exception of deep hepatic coma, did not predict outcome following orthotopic liver transplantation. Seventy variables were assessed at the time of the evaluation. Twenty-three of the 70 variables were found to have prognostic significance with regard to death from progressive liver disease before transplantation. These 23 variables were Incorporated into a multivariate model to provide a means of determining the relative risk of death among pediatric patients with end-stage liver disease. This information may allow more informed selection of candidates awaiting liver transplantation. © 1987 The C. V. Mosby Company

Liver and kidney transplantation in children receiving cyclosporin A and steroids

The new immunosuppressive agent, cyclosporin A, was used with low doses of steroids to treat eight patients undergoing hepatic transplantation and three patients undergoing cadaveric renal transplantation. Seven of the eight liver recipients are well, including one who was given two livers. The three kidney recipients, who had developed cytotoxic antibodies after previously rejecting grafts with conventional immunosuppressive therapy, have had good results despite conditions which usually preclude attempts at transplantation. The ability to control rejection effectively and safely without chronic high-dose steroid therapy may make the described therapeutic regimen valuable for pediatric recipients of whole organs. © 1982 The C. V. Mosby Company

The Expression and Localization of N-Myc Downstream-Regulated Gene 1 in Human Trophoblasts

The protein N-Myc downstream-regulated gene 1 (NDRG1) is implicated in the regulation of cell proliferation, differentiation, and cellular stress response. NDRG1 is expressed in primary human trophoblasts, where it promotes cell viability and resistance to hypoxic injury. The mechanism of action of NDRG1 remains unknown. To gain further insight into the intracellular action of NDRG1, we analyzed the expression pattern and cellular localization of endogenous NDRG1 and transfected Myc-tagged NDRG1 in human trophoblasts exposed to diverse injuries. In standard conditions, NDRG1 was diffusely expressed in the cytoplasm at a low level. Hypoxia or the hypoxia mimetic cobalt chloride, but not serum deprivation, ultraviolet (UV) light, or ionizing radiation, induced the expression of NDRG1 in human trophoblasts and the redistribution of NDRG1 into the nucleus and cytoplasmic membranes associated with the endoplasmic reticulum (ER) and microtubules. Mutation of the phosphopantetheine attachment site (PPAS) within NDRG1 abrogated this pattern of redistribution. Our results shed new light on the impact of cell injury on NDRG1 expression patterns, and suggest that the PPAS domain plays a key role in NDRG1's subcellular distribution. © 2013 Shi et al