Incidence of adverse events with HMG-CoA reductase inhibitors in liver transplant patients.

UNLABELLED: Transplant patients are at increased risk of developing dyslipidemia, which contributes to coronary artery disease and cardiovascular events. The purpose of this study was to explore documented adverse effects of liver transplant recipients receiving lipid-lowering therapies. METHODS: A retrospective chart review of 69 liver transplant patients was conducted to evaluate the incidence of adverse effects, especially rhabdomyolysis and liver function abnormalities, in liver transplant patients treated with a lipid lowering agent (LLA). Data were collected from the time of initiation of LLA to 12 months later, looking at the type, dose, and duration of LLA, concurrent cytochrome P450 inhibitors, immunosuppression used, and laboratory parameters. RESULTS: For HMG-CoA reductase inhibitor therapy, simvistatin was used in five (7.8%) patients, pravastatin in 40 (62.5%), fluvastatin in one (1.6%), atorvastatin in five (7.8%), and lovastatin in three (4.7%). Gemfibrozil, a fibric acid derivative, was employed as monotherapy in 10 (15.6%) of patients. There were five patients who received combination therapy with a fibric acid derivative, four (80%) with gemfibrozil + pravastatin, and one (20%) with gemfibrozil + simvastatin. Six patients studied had adverse effects, five (7.2%) with myalgia and one (1.4%) with myopathy. LLA monotherapy with either pravastatin or atorvastatin was used in these patients. The five patients with myalgia were on concurrent therapy with cyclosporin, and the patient with myopathy was on concurrent cyclosporin + diltiazem therapy, both of which are P450 inhibitors. One out of 23 patients on a non-immunosuppressant P450 inhibitor developed adverse effects. No significant elevation of alanine aminotransferase, aspartate aminotransferase, or alkaline phosphatase was noted in any patient. CONCLUSIONS: Overall, there was a general tolerability with a low incidence of adverse events, no incidence of severe complications, and no alterations in liver function tests in the study population with the use of LLA.

Temporary silastic mesh closure for adult liver transplantation: a safe alternative for the difficult abdomen.

Primary fascial closure is often difficult after adult orthotopic liver transplantation (OLT), complicated by donor-to-recipient graft size mismatch, post-reperfusion hepatic edema, coagulopathy, or intestinal edema. Attempts at closing the abdomen under these circumstances can cause increase in intra-abdominal pressures, resulting in significant complications, including graft loss. Temporary closure with silastic mesh has been used as a viable option in children receiving transplants, but there is no experience recorded with its use in adults. A retrospective review was conducted on 200 consecutive liver transplantations performed over 42 months (October 2002 to February 2006). Records were evaluated for patient and donor demographics, perioperative factors including Model for End-Stage Liver Disease and Child-Turcotte-Pugh scores, indications for OLT, ischemic times, blood product administration, and use of temporary silastic mesh closure. Patients requiring silastic mesh were further evaluated for indication, time to primary fascial closure, duration of intubation, length of stay, graft function, and complications (infectious, vascular, biliary, and hernia development). Comparisons were made with a cohort of patients undergoing OLT over the same time period but who were closed primarily, without the use of temporary silastic mesh. Fifty-one liver transplantations (25.5%) of the 200 total transplant cohort used silastic mesh closure. Comparison of the cohorts (primary closure vs. temporary mesh) revealed that no differences existed, except the requirement of all blood products was significantly greater in the silastic mesh group (P < 0.001). Bowel edema (47.1%) and coagulopathy (37.3%) were the most common indications for mesh closure, with less frequent reasons including donor to recipient size mismatch (11.8%), hemodynamic instability, and a large preexisting fascial defect (2.0% each). The average time from transplant to final fascial closure was 3.4 days (range 2-9 days). In the silastic cohort, 41 transplants where closed primarily, 3 required the addition of synthetic mesh, and 6 had component separation and flap closure. After fascial closure, the mean time to extubation was 1 day. The median length of follow-up was 1.3 years for the silastic closure group. Long-term wound complications in the silastic closure group included 1 instance of colonic fistula, 2 incisional hernias, and 2 wound infections. The 30-day and 1-year patient survival for this group were 93.6 and 82.4%, respectively, and the graft survival for those same periods were 90.2 and 77.7%, respectively. Wound complications, rates of hepatic artery thrombosis or stricture, portal vein thrombosis or stricture, biliary complications, and allograft and patient survival were no different than those in patients undergoing initial primary closure. In adult liver transplantation with a difficult (or potentially difficult) abdomen, temporary closure with silastic mesh was found to allow for uncomplicated fascial closure in a short period of time, with rapid extubation times, excellent graft function, and minimal instances of infectious or wound complications. In circumstances where large amounts of blood products are required, where a size mismatch exists, or where bowel edema is present during adult liver transplantation, temporary closure with silastic mesh is an ideal strategy.