Cerulenin has been shown to reduce body weight and hepatic steatosis in murine models of obesity by inhibiting fatty acid synthase (FAS). We have shown that attenuating intrahepatocyte lipid content diminished the sensitivity of ob/ob mice to ischemia/reperfusion injury and improved survival after liver transplantation. The mechanism of action is by inhibition of fatty acid metabolism by downregulating PPARa , as well as mitochondrial uncoupling protein 2 (UCP2), with a concomitant increase in ATP. A short treatment course of cerulenin prior to I/R injury is ideal for protection of steatotic livers. Cerulenin opens the potential for expanding the use of steatotic livers in transplantation.
Neoral was replaced with a generic cyclosporine formulation on our hospital formulary. We compared outcomes for de novo kidney transplant recipients who either received Gengraf (n=88) or Neoral (n=100) in a single-center, retrospective review. As compared to patients who received Neoral, patients who received Gengraf were significantly more likely to have an acute rejection episode (39% vs. 25%, P=0.04), more likely to have a second rejection episode (13% vs. 4%; P=0.03), or to have received an antibody preparation to treat acute rejection (19% vs. 8%; P=0.02). Patients treated with Gengraf had a higher degree of intrapatient variability for cyclosporine trough concentrations as determined by %CV (P<0.05). The incidence of acute rejection at 6 months posttransplant was significantly higher in patients who received Gengraf compared to Neoral. A larger, prospective analysis is warranted to compare these formulations of cyclosporine in de novo kidney transplant recipients.
Cytomegalovirus (CMV) infection complicates the post-operative course of patients receiving solid organ transplants. While ganciclovir has significantly reduced the direct effects of CMV infection, some patients cannot tolerate the optimal therapeutic exposure required for CMV prevention and treatment. Few reports directly address the incidence, consequences, and risk factors for hematologic toxicities related to ganciclovir therapy. Nevertheless, leukopenia, thrombocytopenia, and anemia occur in 5-50% of patients. Current strategies, focused on ganciclovir dose reduction, may increase the risk of CMV reactivation and drug-resistant disease. The current article reviews the incidence, risk factors, and consequences of ganciclovir-associated hematologic adverse events in transplant recipients. Management strategies, including ganciclovir dose reduction, and the addition of CMV hyperimmune globulin are discussed. Exposing this relatively frequently occurring, but uncommonly discussed, toxicity should lead to better avoidance and treatment strategies, without placing patients at increased risk of CMV disease.
Hepatic artery thrombosis (HAT) is the most common vascular complication after orthotopic liver transplantation (OLT) and has traditionally been managed with re-OLT. However, several reports have shown that urgent revascularization is frequently an effective means of graft salvage. This most often involves hepatic artery (HA) thrombectomy and thrombolysis, with reestablishment of arterial inflow through a donor iliac artery conduit based on the supraceliac or infrarenal aorta. We report a 46-year-old man who developed HAT 13 days after OLT after angiographic splenic artery embolization to reduce splenic artery steal. A suitable donor iliac artery was not available for arterial reconstruction and could not be obtained from neighboring transplant centers. The patient underwent urgent HA thrombectomy, intrahepatic arterial thrombolysis, and revascularization using an autologous radial artery (RA) conduit based on the supraceliac aorta. The patient is alive more than 1 year after revascularization, with normal liver function and documented flow in the arterial conduit by Doppler ultrasound and arteriography. He has not developed late biliary complications or adverse sequelae of RA harvest. Autologous RA can be safely and successfully used as an aortic-based arterial conduit in urgent revascularization of HAT after OLT. RA should be considered for use in HA revascularization if an adequate donor iliac artery is not available and other potential conduits are not usable or desirable. The availability of autologous RA expands the armamentarium of vascular conduits that can be used in HA revascularization and may help minimize re-OLT for otherwise potentially salvageable liver allografts. (Liver Transpl 2001;7:913-917.) H epatic artery (HA) thrombosis (HAT) is the most common vascular complication in orthotopic liver transplantation (OLT), with an incidence of 2% to 5% in adults and 10% to 33% in children. 1 Although interruption of HA flow is frequently well tolerated in a native liver because of the presence of collateral arterial blood supply, it is often a morbid and life-threatening event after OLT because of the lack of collateral vessels. Although it has been speculated that as many as one third of all early cases of HAT after OLT may be asymptomatic, 2 many episodes of HAT result in either acute hepatic necrosis and liver failure or late biloma and hepatic abscess formation. Traditionally, HAT has been considered an indication for urgent re-OLT, and most cases are still managed in this way. Although re-OLT has significantly reduced the morbidity and mortality attributable to HAT, this option has become limited by the decreasing availability of organs for transplantation. Over the past decade, several reports have shown the effectiveness of urgent revascularization for early HAT. [2][3][4][5][6] Although HA thrombectomy with primary reanastomosis is well described, revascularization usually requires the use of a donor iliac artery as a vascular conduit between the aorta and allograft HA.We report a novel approach ...
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