Ischemia/reperfusion (IR) injury in transplanted livers contributes to organ dysfunction and failure and is characterized in part by loss of NO bioavailability. Inhalation of NO is nontoxic and at high concentrations (80 ppm) inhibits IR injury in extrapulmonary tissues. In this prospective, blinded, placebo-controlled study, we evaluated the hypothesis that administration of inhaled NO (iNO; 80 ppm) to patients undergoing orthotopic liver transplantation inhibits hepatic IR injury, resulting in improved liver function. Patients were randomized to receive either placebo or iNO (n = 10 per group) during the operative period only. When results were adjusted for cold ischemia time and sex, iNO significantly decreased hospital length of stay, and evaluation of serum transaminases (alanine transaminase, aspartate aminotransferase) and coagulation times (prothrombin time, partial thromboplastin time) indicated that iNO improved the rate at which liver function was restored after transplantation. iNO did not significantly affect changes in inflammatory markers in liver tissue 1 hour after reperfusion but significantly lowered hepatocyte apoptosis. Evaluation of circulating NO metabolites indicated that the most likely candidate transducer of extrapulmonary effects of iNO was nitrite. In summary, this study supports the clinical use of iNO as an extrapulmonary therapeutic to improve organ function following transplantation.

The influence of ethnic origin on organ donation and renal allograft survival after renal transplantation has been controversial. Several large studies have reported inferior renal allograft survival in black recipients, whereas others have reported equal survival. However, the issue of race as it relates to organ donation, patient referral, and patient selection in orthotopic liver transplantation has not been investigated. We retrospectively reviewed our results of organ donation, patient referral and selection, and orthotopic liver transplantation since 1989. Because of a concerted educational effort by this organ procurement organization, the percentage of black donors has increased from 6.1% in 1988 to 21.9% in 1996. Since the inception of the Liver Transplant Program in 1989, 844 patients have been referred to our transplant center for organ transplant evaluation. Disproportionately fewer black patients (119; 14.1%) were referred for liver transplantation than white patients (725; 85.9%) based on the prevalence of end-stage liver disease in these populations. The acceptance rate for listing for transplantation was similar between the two groups. The percentage of patient referrals who actually underwent transplantation was similar across racial lines (43% black v 42% white patients). However, it appeared that black patients were referred for liver transplantation at a later stage and were more critically ill at the time of referral. Nevertheless, the patient and graft survival were similar between black and white patients. The 1-and 3-year survival rates in white recipients was 88% and 81%, respectively, versus 96% and 84% in black recipients. Within this organ procurement organization, black donation has increased over the past 10 years. Unfortunately, there may be a selection bias at the level of referral for liver transplantation. However, once patients are referred to this center for liver transplantation, the rate of transplantation and survival is similar between white and black patients.

Combination therapy with tacrolimus and MMF may significantly reduce the incidence of acute liver allograft rejection, allow a significant reduction in tacrolimus dosage, and decrease the incidence of nephrotoxicity. Long-term analysis will be necessary to assess any increased risk of opportunistic infections.

No abstract

In the pilot study, induction therapy with daclizumab was safe, facilitated improvement in renal function, and appeared to reduce the incidence of acute rejection. Combination therapy with daclizumab may be an important adjunct in immunosuppressive strategies for liver transplant recipients.