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Liver transplants are associated with a high incidence of fungal infections - as high as 28 percent. Prolonged use of antibiotics, indwelling catheters and immunosuppressive therapy may predispose the transplant recipient to these fungal infections. A retrospective study was undertaken of 307 liver transplant patients to determine the incidence and severity of these fungal infections, identify risk factors, and evaluate outcome and treatments. There were 91 infections identified in 72 liver transplants (23.8 percent). Candida, an organism normally found in the gastrointestinal tract and other areas of the body, was responsible for 83.5 percent of the infections. The infections included generalized infection (19 cases), inflammation of the abdominal cavity (17), and inflammation of the lungs (15). The infection was identified within the first two months in 84.7 percent of cases; the average was 16 days after transplant. Early identification is a problem; the main clinical problem was widespread infection. Risk factors identified included: retransplantation, reintubation, need for blood transfusion during surgery, urgent need for the operation, as well as number of steroid doses given, bacterial infection with antibiotic treatment, and vascular complications. Fungal infection was associated with decreased survival; 50 percent, versus 16.5 percent of patients without fungal infection. Treatment with amphotericin B was successful in 63 cases (74.1 percent). These findings indicate that fungal infection is a major cause of morbidity and mortality in liver transplant patients; this is related to specific risk factors, suggesting the need for effective preventive measures. (Consumer Summary produced by Reliance Medical Information, Inc.)

Cytomegalovirus (CMV) has become the most important infectious agent in patients who undergo organ transplantation, due, in large measure, to the immunocompromised condition of the host. Infection with CMV may be the result of exposure to infected blood products or the transplanted organ, of reactivation of latent virus, or of reinfection. Liver transplant patients often develop infections, which are a serious cause of illness and death. To learn more about CMV disease among liver transplant recipients, the records of 211 patients (127 adults, 84 children) at one medical facility were reviewed. Patients were followed-up for an average of 13 months. Thirty-seven retransplantation procedures were performed for the whole group. When CMV disease was diagnosed, antiviral therapy with intravenous ganciclovir was initiated and patients' clinical, viral, and tissue biopsy results noted. Results showed that 73 patients (34.6 percent) experienced at least one episode of CMV disease, with a slightly higher incidence among adults. The diseases that necessitated liver transplantation are enumerated; in adults, there was no diagnosis consistently associated with subsequent CMV disease. In children, however, postnecrotic cirrhosis (a degenerative condition associated with tissue death) tended to be followed by CMV disease more than other disorders, with a lower CMV disease frequency among children with metabolic disorders. The risk of CMV disease was highest in patients who received livers from donors whose blood tested positive for CMV, from those who underwent treatment with agents to suppress lymphocyte proliferation for immunosuppression, and from those who underwent retransplantation. Primary disease (11 people) usually developed in the transplanted liver and had a high recurrence rate; however, it responded to ganciclovir in all cases. Control of CMV disease by this drug was achieved in approximately 94 percent of all cases. A discussion is provided of CMV disease in transplant recipients, and the lack of information regarding the effects of ganciclovir on liver transplant recipients is noted. Prompt diagnosis and preventive therapy are the key elements of treating this disorder in such patients. (Consumer Summary produced by Reliance Medical Information, Inc.)

With current immunosuppressive regimens, viral disease has become an important source of morbidity after orthotopic liver transplantation. Over a 5‐year period, we retrospectively analyzed 422 liver transplants in 370 recipients (242 adults, 128 children) under cyclosporine and prednisone immunosuppression. A total of 108 patients (29.2%) received intravenous ganciclovir for viral disease, including 103 for cytomegalovirus (CMV) disease and 5 for Epstein‐Barr virus (EBV) disease. A total of 132 episodes of CMV disease (103 initial, 29 relapse) were treated with ganciclovir, including 22 patients with primary CMV disease. Opportunistic viral hepatitis was the most common clinical presentation of viral disease while recurrent disease often involved extra‐hepatic sites (especially pulmonary). The majority of cases of viral disease (both initial and relapse) were confined to single organ involvement (81.0%), at which time ganciclovir therapy was begun at a dose of 5 mg/kg twice daily for 2 weeks (with dosage adjustments for renal dysfunction). The initial diagnosis of CMV disease was made at a mean time after transplantation of 38 days, with a mean duration of ganciclovir therapy of 16 d. A prompt and lasting response, characterized by clinical improvement and negative viral cultures, was documented in 74 cases (71.8%). Fourteen additional patients were successfully retreated with ganciclovir for CMV relapse, so that CMV disease was ultimately controlled in 85.4% of cases. EBV disease was diagnosed at a mean time of 124 d after transplantation, with a mean duration of ganciclovir therapy of 39 d. Four cases (80%) were successfully treated. Overall patient survival after ganciclovir therapy is 79.0% with a mean follow‐up of 24 months. Adverse drug effects included significant leukopenia and thrombocytopenia in 7 patients (6.5%), with 2 requiring drug withdrawal. Conclusion: ganciclovir is a safe and effective agent for the treatment of viral disease in liver transplantat recipients. The availability of ganciclovir has resulted in successful treatment of viral disease without dramatic reductions in immunosuppression, thus permitting successful rescue of the patient and allograft with an acceptably low incidence of toxicity and viral relapse.

• The use of OKT3 therapy is a major risk factor for opportunistic infections in liver transplant recipients. In the last 2 years, we prospectively randomized 100 patients receiving OKT3 therapy into either a control group (n = 50) or a prophylaxis group (n=50). Prophylaxis consisted of six doses of intravenous immune globulin over 4 weeks and oral acyclovir for 3 months after OKT3 therapy. The two groups were comparable with respect to demographic, immunologic, and clinical characteristics. The regimen of prophylaxis resulted in (1) a significant reduction in the incidence of herpetic and Epstein-Barr viral infections; (2) no change in the incidence of cytomegalovirus infections; (3) a significant decrease in the incidence of fungal infections; and (4) fewer deaths due to sepsis. The incidence of viral and fungal infections was higher after OKT3 induction than after rescue therapy. Our conclusion is that opportunistic infections are frequent after OKT3 therapy in hepatic allograft recipients. Treatment with intravenous immune globulin and oral acyclovir is safe and effective in preventing noncytomegaloviral and fungal infections in this setting, thus conferring a survival advantage with fewer deaths due to sepsis.(Arch Surg. 1992;127:55-64)

• The causes of death in 21 adults and 23 children in a consecutive series of 180 liver transplantations were reviewed and classified into four categories. A previously described preoperative risk score was applied prospectively to estimate the relative risk of mortality following liver transplantation in adults. Categorization of the causes of death allowed for a systematic search for errors in management and technique. Comparison of the preoperative risk score with the cause of death category revealed that higher-risk adults were most likely to die of causes related to preoperative morbidity. They also accrued higher hospital costs, regardless of outcome. The data are useful for designing strategies to reduce mortality. However, the inexorable role that preoperative morbidity has on outcome was also emphasized. This has important implications in developing strategies to reduce the costs of liver transplantation and to provide optimal distribution of scarce donor organs.(Arch Surg. 1989;124:895-900)