The aim of this study was to investigate the variability of the voriconazole plasma level and its relationships with clinical outcomes and adverse events among liver transplant recipients to optimize the efficacy and safety of their treatment. Liver transplant recipients treated with voriconazole were included, and voriconazole trough levels were quantified by a validated high-performance liquid chromatography method. Cytochrome P450 genotypes for CYP2C19 were evaluated in allograft liver tissues. A total of 832 voriconazole trough levels from 104 patients were measured. Proven, probable, and possible invasive fungal infections were reported for 8/104 (7.7%), 42/104 (40.4%), and 54/104 (51.9%) patients, respectively. Receiver operating characteristic (ROC) curve analysis indicated that trough concentrations of ≥1.3 μg/ml minimized the incidence of treatment failure (95% confidence interval [CI], 0.68 to 0.91 μg/ml) ( < 0.001) and that those of <5.3 μg/ml minimized the incidence of any adverse events (95% CI, 0.83 to 0.97 μg/ml) ( < 0.001). Voriconazole trough levels were significantly higher for heterozygous extensive metabolizers, poor metabolizers, and individuals receiving coadministration with proton pump inhibitors. For ultrarapid metabolizers, oral administration of voriconazole, and concomitant use of glucocorticoids, voriconazole blood concentrations were significantly reduced. Furthermore, there was no statistically significant association of patient age, weight, or gender or coadministration of tacrolimus and cyclosporine with the voriconazole trough level. In conclusion, the results of our analysis indicate large inter- and intraindividual variabilities of voriconazole concentrations in liver transplant recipients. Voriconazole trough concentrations of ≥1.3 μg/ml and <5.3 μg/ml are optimal for treatment and for minimization of adverse events. Optimization of drug efficacy and safety requires the use of rational doses for voriconazole therapy.
Background:Among the opportunistic microorganisms, fungi, particularly Candida, play an important role in the mortality of transplant recipients. Thus, controlling and preventing fungal colonizations in various parts of the body, including the oral cavity, can reduce the possibility of post-transplant invasive fungal infections. This can be done simply by using mouthwashes.Objectives:The current study aimed to determine the prevalence of fungal species of Candida within the oral cavities of liver transplant recipients, and to evaluate the effects on Candida colonization of different exposure times to common mouthwashes.Patients and Methods:Specimens were taken from the oral cavities of 101 liver transplant recipients who were referred to our clinic for their first monthly examination. After cultivation and DNA extraction, yeast strains were identified with the RFLP technique. Each strain’s susceptibility to 0.2% chlorhexidine, Vi-One, Oral-B, Nanosil D1, and Nystatin mouthwashes was determined based on the CLSI M27-A2 standard method.Results:The obtained data were analyzed using SPSS. Out of 101 samples from liver transplant recipients, 68 cases showed fungi growing within the culture media (67.4%). C. albicans and C. glabrata, respectively, were the first and second most frequent types. Mouthwash susceptibility tests revealed that their antifungal effects over 60 seconds were significantly higher than with an exposure time of 30 seconds. At both 30 and 60 seconds, chlorhexidine was significantly the most efficient.Conclusions:Chlorhexidine mouthwash with an exposure time of 60 seconds or more is suggested as an effective antifungal agent to be included in the medication regimen of liver transplant patients pre- and postoperatively, in order to prevent fungal colonization and subsequent systemic infections.
Objectives: Evidence exists that decreased in triiodothyronine (T3) and thyroxine (T4) levels are associated with the severity of liver disease, and these hormones could be used as disease prognostic factors, but there are paradoxes in this regard in the literature. This study aimed at evaluating the correlation between thyroid hormone levels and severity of liver disease. Materials and Methods:We measured thyroid hormone levels in 83 children with liver cirrhosis using radioimmunoassay techniques. Results: Four patients (4.8%) showed a decrease in the amount of T3 and 9 patients (10.8%) revealed increased levels of T3. Also, decreases were seen in the T4 levels of 7 patients (8.4%), and 4 patients (4.8%) showed increases in levels of T4. The serum albumin levels were lower and international normalized ratio was higher in patients with low T3 and low T4. This study reveals that the Model for End-Stage Liver Disease and Pediatric End-Stage Liver Disease scores are statistically related to the decreased amounts of T4 (P = .036). The Model for End-Stage Liver Disease and Pediatric End-Stage Liver Disease scores and the Child scores were higher in low T3 patients, but this was not significant (P > .05). Conclusions: Decreased levels of thyroid hormones are correlated with the severity of disease and can be seen in more advanced cirrhosis. Patients with decreased T4 levels need a liver transplant more immediately than those patients that do not have decreased T4 levels.
Objectives: Metabolic syndrome components, such as being overweight or having hypertension, hyperlipidemia, or diabetes mellitus, are common complications after liver transplant in pediatric patients with probable multifactorial causes and increase the risk of cardiovascular complications in adulthood. In this study, our aim was to evaluate the prevalence of these components both before and after transplant surgery. Materials and Methods: Our study included all children having liver transplant at our institution over a period of 20 years who were under 18 years old and had at least 6 months of posttransplant follow-up. Prevalence of metabolic syndrome components and pretransplant and posttransplant laboratory data of patients were evaluated. Results: Over the 20-year study period, 391 liver transplant patients were included in our study, in which 167 were girls (42.7%) and 224 were boys (57.3%). Patients showed a posttransplant hyperlipidemia rate of 7.5%, hyperglycemia rate of 22%, hypertension rate of 9.6%, and metabolic syndrome rate of 50.2%. Pretransplant, the rate of patients with metabolic syndrome was 10.5%. Conclusions: Our study confirmed that the prevalence of metabolic syndrome in patients after liver transplant increases dramatically and should be explored with further research.
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