Sixty-two adults who underwent orthotopic liver transplantations between February 1981 and June 1983 were followed for a mean of 170 days after the operation. Twenty-six patients developed 30 episodes of significant fungal infection. Candida species and Torulopsis glabrata were responsible for 22 episodes and Aspergillus species for 6. Most fungal infections occurred in the first month after transplantation. In the first 8 weeks after transplantation, death occurred in 69% (18/26) of patients with fungal infection but in only 8% (3/36) of patients without fungal infection (P less than 0.0005). The cause of death, however, was usually multifactorial, and not solely due to the fungal infection. Fungal infections were associated with the following clinical factors: administration of preoperative steroids (P less than 0.05) and antibiotics (P less than 0.05), longer transplant operative time (P less than 0.02), longer posttransplant operative time (P less than 0.01), duration of antibiotic use after transplant surgery (P less than 0.001), and the number of steroid boluses administered to control rejection in the first 2 posttransplant months (P less than 0.01). Patients with primary biliary cirrhosis had fewer fungal infections than patients with other underlying liver diseases (P less than 0.05). A total of 41% (9/22) of Candida infections resolved, but all Aspergillus infections ended in death.

Advances in the management of both chronic and acute hepatic disease have been made possible and even mandated by the development of liver transplantation. The clinical use of transplantation has proceeded at a rapid pace since a Consensus Development Conference of the National Institutes of Health concluded in June 1983 that liver transplantation had become a service and not simply an experimental procedure. 1 The liver can be transplanted as an extra (auxiliary) organ at an ectopic site, or in the orthotopic location after the removal of the host liver (Fig. 1). This article will focus primarily on the orthotopic procedure. However, there has been renewed interest in the auxiliary operation, which will be discussed separately. Candidacy for TransplantationThe conceptual appeal of liver transplantation is so great that the procedure may come to mind as a last resort for virtually every patient with lethal hepatic disease. The selection of appropriate recipients from such a large pool requires strict individual assessment. A 1982 estimate of the annual need for liver transplantation was 15 per million population, 2 but the current need is undoubtedly higher because there are now fewer restrictions on candidacy. Between 4000 and 50,000 liver transplantations a year may be needed in the United States.The supply of organs will increasingly influence the criteria for candidacy and limit the use of the procedure. Discussions about rationing transplantation services for this reason are nonetheless premature, because the balance between need and supply has not been determined. In the United States, the yearly rate of liver transplantation has reached approximately 1600; it averaged 147 a month between July and December 1988 (Vaughn W, United Network of Organ Sharing: personal communication). The annual rate in Europe approaches this figure.Policies on organ donation will have to be reexamined if substantial growth is to occur. Many potential liver donors are probably rejected unjustifiably. The arbitrary upper age limit observed by most programs 3 cannot be justified, because senescence largely spares the liver. 4 Atherosclerosis of the hepatic arteries is not usually found beyond the origin of the celiac axis. 4 Our own limited experience with livers from donors over 50 years old has been encouraging.

Autoimmune chronic active liver disease (ACALD), a major indication for liver transplantation, is associated strongly with antigenic determinants HLA-B8 and DR3. A retrospective analysis of 43 patients who underwent OLTx for putative ACALD and who, as well as their tissue organ donors, were typed, was performed. Disease recurrence and graft rejection episodes were determined by chart review and histopathological review of all material available. Disease recurrence was histologically documented in 11 (25.6%) of these 43 cases. Graft rejection episodes occurred in 24 (55.8%). All recurrences were in recipients of HLA-DR3-negative grafts. Nine of the recurrences were in HLA-DR3-positive recipients (odds ratio: 6.14, P less than 0.03). Two of 11 cases of disease recurrence were in recipients who were HLA-DR3-negative. Nine of these 11 had received HLA-DR3-negative grafts. Rejection occurred in 13 HLA-B8-positive recipients, 12 of whom received HLA-B8-negative grafts. Eleven HLA-B8-negative recipients experienced at least one rejection episode and 9 of these had received HLA-B8-negative grafts. Based upon these data we conclude: 1) that recurrence of putative ACALD is more likely to occur in HLA-DR3-positive recipients of HLA-DR3-negative grafts; (2) that recurrences were not seen in recipients of HLA-DR3-positive grafts; (3) that HLA-B8 status does not affect disease recurrence; and (4) that neither the HLA-B8 nor the DR3 status of the graft or recipient has an effect on the observed frequency of rejection.

To determine the basis for low serum con-

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