Sirolimus and cardiovascular disease risk in liver transplantation.

BACKGROUND: Two adverse effects of sirolimus are hypertriglyceridemia and hypercholesterolemia. These elevated levels often lead clinicians to discontinue the sirolimus from concerns of an increased cardiovascular disease (CVD) risk; however, evidence suggests that sirolimus might be cardioprotective. There are no published reports of sirolimus CVD in liver transplantation. METHODS: We reviewed all 1812 liver recipients who underwent transplantation from 1998 to 2010, identifying a cohort using sirolimus as part of the initial immunosuppression (SRL Cohort) and a control group of the remaining patients from this period where SRL was never given (Non-SRL Control). A prospectively maintained database identified all episodes of myocardial infarction (MI), congestive heart failure (CHF), abdominal aortic aneurysm (AAA), and cerebrovascular accident and tracked triglyceride, high-density and low-density lipoproteins, and total cholesterol levels. A Framingham Risk Model calculated the predicted 10-year risk of CVD for both groups. RESULTS: The SRL Cohort (n=406) is older, more predominantly male, with more pretransplantation hypertension and diabetes and posttransplantation hypertension compared to Non-SRL Controls (n=1005). The SRL Cohort has significantly higher triglyceride, low-density lipoprotein, and cholesterol levels at 6 months and 1 year. There is no difference in MI incidence in the SRL Cohort (1.0% vs. 1.2%) and no difference in AAA, cerebrovascular accident, and CHF. The Framingham Risk Model predicts that the SRL Cohort should have almost double the 10-year risk of CVD compared to the Non-SRL Control (11% vs. 6%). CONCLUSIONS: Sirolimus causes hypertriglyceridemia and hypercholesterolemia, but it does not increase the incidence of MI or other CVDs. Considering the SRL Cohort has more cardiac risk factors and nearly double 10-year predicted CVD risk, the fact that the CVD incidence is similar suggests that sirolimus is in fact cardioprotective.

Long-term follow-up of liver transplantation for Budd-Chiari syndrome with antithrombotic therapy based on the etiology.

BACKGROUND: Because myeloproliferative disorders (MPDs) are a frequent cause of Budd-Chiari syndrome (BCS), treatment directed toward altering platelet production and function may be more rational and effective than anticoagulation after liver transplantation. METHODS: We reviewed data on 25 patients who received liver transplantation for BCS at our institution from 1987 to 2007. Posttransplant antithrombotic treatment was based on the cause of BCS: 17 patients with MPDs received hydroxyurea/aspirin; 5 received warfarin; and 3 (2 whose hypercoagulable disorder was corrected and 1 with sarcoidosis) received no therapy. RESULTS: Both graft survival (88% at 5 years) and patient survival (92% at 5 years) were superior in the BCS group compared with the 2609 patients who received liver transplants for other indications. Vascular complications included three instances of hepatic artery stenosis (NS compared with non-BCS liver recipients), one of portal vein thrombosis (nonsignificant [NS]), and one of portal vein stenosis (NS). All 25 patients underwent multiple liver biopsies with no bleeding complications. CONCLUSIONS: Using hydroxyurea and aspirin to treat patients with BCS caused by an MPD seems to be safe and effective and avoids the risks of anticoagulation with warfarin.