Search

Objectives. Tacrolimus is characterized by high pharmacokinetic variability in combination with a narrow therapeutic range. However, influence of donor CYP3A5 genotype and graft-to-recipient body weight ratio (GRWR) on tacrolimus' pharmacokinetics after pediatric living donor liver transplantation (LDLT) remains unclear. Methods. A total of 174 LDLT recipients (<6 y) were grouped according to donor CYP3A5 genotypes (nonexpressor (NEX) or expressor (EX)) and GRWR (<3.0% (SS, small-size) or ≥3.0% (LS, large-size)): SS/NEX (n = 40), SS/EX (n = 38), LS/NEX (n = 48), and LS/EX (n = 48). Pharmacokinetics of tacrolimus and clinical outcomes were analyzed. Results. The relationships between the concentration-dose ratio and donor CYP3A5 genotypes and graft size were examined 3, 7, 14, and 30 days after the transplantation. Tacrolimus C0 levels varied greatly among groups, although recipients started with the same initial dosage. LS/EX recipients had significantly lower C0 levels in comparison with those of other groups. The use of CYP3A5-EX-grafts and a greater GRWR both resulted in significantly higher TAC dose requirements and lower C/D ratios. However, the significance of GRWR no longer exists 3 months after transplantation. The multivariate generalized linear mixed model analysis showed that donor CYP3A5 genotypes (F = 11.876 ; P = 0.01) and GRWR (F = 4.631 ; P = 0.033) were independent impact factors for C/D ratios 3, 7, 14, and 30 days after transplantation. Donor CYP3A5-EX genotype was associated with significantly increasing risks of infectious complications and significantly lower Cylex ATP values. However, no significant difference was observed in acute rejections among 4 groups. Conclusions. Monitoring of C0 levels alone is not reliable to guide tacrolimus administration. Donor CYP3A5 and GRWR both significantly affect tacrolimus pharmacokinetics after pediatric LDLT. The use of Cylex ATP tests would be helpful to avoid overimmunosuppression. [ABSTRACT FROM AUTHOR]

Glycogen storage disease (GSD) is a rare disease that can cause life-threatening problems owing to metabolic errors in storing or using glycogen. The disease course of GSD remains unknown, despite medical technology advances. We determined the prevalence and complications of GSD using data from the National Health Insurance Service database. Data were collected and analyzed for the entire South Korean population with GSD during 2007–2018. GSD was defined as a combination of disease code E74.0 and rare incurable disease insurance code V117, a unique disease code combination for GSD in South Korea. Overall, 23,055 patients had the E74 disease code; 404 had an additional V117 insurance code. Most GSD patients were aged <10 years. Many complications were identified, the most common being hepatomegaly, hyperuricemia, and elevated liver enzyme levels. The most prescribed drug was α-glucosidase, followed by allopurinol. Seventy-two percent of patients were treated in pediatrics. Twenty-five patients underwent liver transplantation, and 14 died after GSD diagnosis. In South Korea, more patients than expected had GSD diagnosis and were managed accordingly. GSD causes many complications and hospitalizations, resulting in high medical expenses. Serious complications can result in liver transplantation and, eventually, death in some cases. Although the patients' condition was identified only by the disease code, this is the first study to present the current situation of GSD patients in South Korea. Because GSD patients can have dangerous medical conditions, they should be managed consistently while minimizing various complications that may occur with optimal metabolic control. [ABSTRACT FROM AUTHOR]

Objective. To analyze the diagnosis and treatment of patients with concomitant malignant tumors after organ transplantation by compiling data from organ transplantation patients. Methods. By searching CNKI and PubMed databases, we made a systematic analysis of the studies of postorgan transplantation complicating malignant tumors in the last decade. Results. There were 10 articles on malignant tumors after renal transplantation, 8 articles on liver transplantation, 2 articles on heart transplantation, and 1 article on lung transplantation. The incidence of malignant tumors complicating renal transplantation is 10.4% in Europe, with skin cancer and Kaposi's sarcoma being common; the incidence in the United States is 3.4%, with PTLD having the highest incidence; the incidence of malignant tumors is relatively lowest in Asia, with gastrointestinal malignancies being the main ones. The mean time to complication of malignancy after renal transplantation is 3.83 years. The incidence of concurrent malignancies after liver transplantation is 8.8% in Europe, where skin cancer and Kaposi's sarcoma are common; 5.6% in Asia, where gastrointestinal tract tumors are prevalent; and 4.5% in the United States, where gastrointestinal tract tumors, PTLD, and hematologic diseases are predominant. The mean time to complication of malignancy after liver transplantation is 4.79 years. The incidence of malignancy after heart transplantation is 6.8-10.7%. The incidence of malignancy after lung transplantation is about 10.1%. Minimization of immunosuppression or modification of immunosuppression regimens may be a key component of cancer prevention. mTOR inhibitors and phenolate (MMF) reduce the incidence of de novo malignancies in patients after solid organ transplantation. Surgical treatment improves survival in patients with early malignancies. The use of external beam radiation therapy in the treatment of hepatocellular carcinoma is limited due to the risk of radiation liver disease. Conclusions. The risk of concomitant malignancy needs to be guarded for 5 years of immunosuppressive therapy after organ transplantation surgery. Adjusting the immunosuppressive treatment regimen is an effective way to reduce concurrent malignancies. Systemic chemotherapy or radiotherapy requires vigilance against the toxic effects of drug metabolism kinetics on the transplanted organ. [ABSTRACT FROM AUTHOR]

This study is aimed at determining the ability of computed tomography- (CT-) based radiomic analysis to distinguish between grade 0/1 and grade 2/3 macrovesicular steatosis (MaS) in cadaveric donor liver transplantation cases. Preoperative noncontrast-enhanced CT images of 150 patients with biopsy-confirmed MaS were analyzed retrospectively; these patients were classified into the low-grade MaS (n = 100 , grade 0 or 1) and high-grade MaS (n = 50 , grade 2 or 3) groups. Three-dimensional spherical regions of interest of 40 pixel (2.5 cm) in diameter were placed in the right anterior and left lateral segments of the liver. Thereafter, 300 regions of interest (ROIs) were segmented and randomly assigned to the training and testing groups at a ratio of 7 : 3. A total of 402 radiomic features were extracted from each ROI. For MaS classification, a radiomic model was established using multivariate logistic regression analysis. Clinical data, including age, sex, and liver function, were collected to establish the clinical model at the patient level. The performances of the radiomic and clinical models, i.e., the diagnostic discrimination, calibration, and clinical utilities, were evaluated. The radiomic model, with seven selected features, depicted a good discrimination with an area under the receiver operating characteristic curve (AUC) of 0.907 (95% confidence interval (CI): 0.869–0.940) in the training cohort and 0.906 (95% CI: 0.843–0.959) in the testing cohort. The calibration curve revealed good agreement between the predicted and observed probabilities in the training and testing cohorts (both P > 0.05 in the H-L test). Decision curve analysis revealed that the radiomic model was more beneficial than the treat-all or treat-none schemes for predicting the MaS grade. Alanine transaminase and gamma-glutamyl transferase were used for building the clinical model, and the AUC was 0.784 in the total cohort. The CT-based radiomic model outperforming the conventional clinical model could provide an important reference for MaS grading in cadaveric liver donors. [ABSTRACT FROM AUTHOR]

Background. The suspension of the surgical activity, the burden of the infection in immunosuppressed patients, and the comorbidities underlying end-stage organ disease have impacted transplant programs significantly, even life-saving procedures, such as liver transplantation. Methods. A review of the literature was conducted to explore the challenges faced by transplant programs and the adopted strategies to overcome them, with a focus on indications for imaging in liver transplant candidates. Results. Liver transplantation relies on an appropriate imaging method for its success. During the Coronavirus Disease 2019 (COVID-19) pandemic, chest CT showed an additional value to detect early signs of SARS-CoV-2 infection and other screening modalities are less accurate than radiology. Conclusion. There is an emerging recognition of the chest CT value to recommend its use and help COVID-19 detection in patients. This examination appears highly sensitive for liver transplant candidates and recipients, who otherwise would have not undergone it, particularly when asymptomatic. [ABSTRACT FROM AUTHOR]