Feasibility of steroid-free tacrolimus-basiliximab immunosuppression in pediatric liver transplantation and predictors for steroid requirement.

Avoidance of steroids in pediatric liver transplantation may reduce toxicity and morbidity. The aim of this study was to analyze the feasibility of a steroid-free tacrolimus-basiliximab immunosuppression scheme, the risk factors associated with steroid requirement, and safety parameters. Patients who underwent liver transplantation for biliary atresia between 2011 and 2019 were included and followed for 6 months after transplantation. Immunosuppression consisted of tacrolimus-based treatment with basiliximab induction. Steroid-free survival was estimated, and risk factors for steroid requirement were evaluated using multivariate Cox regression analysis. A total of 76 patients were included, of whom 42 (55.3%) required steroids (>14 d) due to biopsy-proven acute rejection (47.6%, n = 20), instability in liver function tests (35.7%, n = 15), tacrolimus-related adverse drug reactions (14.3%, n = 6), or other reasons (bronchospasm episode, n = 1). Steroid-free survival was 45.9% (95% CI, 35.9-58.8). Independent factors associated with steroid requirement included tortuosity in tacrolimus trough levels (≥1.76 vs. <1.76: HR 5.8, 95% CI, 2.6-12.7; p < 0.001) and mean tacrolimus trough levels (≥ 6.4 ng/mL vs. < 6.4 ng/mL: HR 0.4, 95% CI, 0.2-0.7; p = 0.002). The rate of bacterial and viral infections was comparable between patients with and without steroids, although in the former group, cytomegalovirus infection developed earlier ( p = 0.03). Patients receiving steroids had higher total cholesterol, LDL, and HDL levels ( p < 0.05) during follow-up, but no changes in the height Z-score were observed 1 year after transplantation. Basiliximab induction in combination with tacrolimus-based treatment avoided steroid requirements in 45% of the patients. Tacrolimus variability and trough levels below 6.4 ng/mL independently increased the risk of steroid requirement. Further efforts should be focused on personalizing immunosuppressive treatment.

Prognostic Factors in Pediatric Early Liver Retransplantation.

The most common indications for early liver retransplantation (eRe-LT) are vascular complications and primary nonfunction (PNF). These patients are usually in a critical clinical condition that can affect their chances of survival. In fact, the survival of these patients is usually lower compared with the patients undergoing a first transplant. To the best of our knowledge, no specific series of pediatric patients undergoing eRe-LT has been published to date. Therefore, the aim of this study is to report the results of eRe-LT and to analyze factors potentially related to success or failure. Our work is of a retrospective cohort study of patients who underwent eRe-LT at the Juan P. Garrahan Pediatric Hospital of Buenos Aires, Argentina, between May 1995 and December 2018 (n = 60). Re-LT was considered early when performed ≤30 days after the previous LT. A total of 40 (66.7%) patients were enrolled due to vascular causes and 20 (33.3%) were enrolled because of PNF. Of all the relisted patients, 36 underwent eRe-LT, 14 died on the waiting list, and 10 recovered without eRe-LT. A total of 23 (63.9%) patients died after eRe-LT, most of them due to infection-related complications. Survival rates at 1 and 5 years were 42.4% and 33.9%, respectively. On univariate logistic regression analysis, Pediatric End-Stage Liver Disease (PELD)/Model for End-Stage Liver Disease (MELD) scores, transplant era, and advanced life support at eRe-LT were found to be related to 60-day mortality. However, on multivariate analysis, era (odds ratio [OR], 9.3; 95% confidence interval [CI], 1.19-72.35; P = 0.033) and PELD/MELD scores (OR, 1.07; 95% CI, 1-1.14; P = 0.036) were significantly associated with 60-day patient mortality. This study found that the level of acuity before retransplant, measured by the requirement of advanced life support and the PELD/MELD score at eRe-LT, was significantly associated with the chances of post-eRe-LT patient survival.

Prognostic factors for event-free survival in liver transplantation for hepatoblastoma: A single-center experience.

Hepatoblastoma (HB) is the most common malignant liver tumor in children. Twenty percent of the cases may remain unresectable after neoadjuvant chemotherapy and, for these patients, liver transplant (LT) is an accepted therapeutic option. To analyze the risk factors to event-free survival (EFS) that influence the clinical outcome of patients with HB receiving LT, we retrospectively analyzed 21 patients with HB who underwent LT between January 1, 2005, and May 1, 2018. Overall survival (OS) was 90%. The univariate analysis shows that the AFP level at the time of LT was associated with a higher risk of EFS. With a ROC curve analysis, we established a cutoff point value of AFP levels at 16 000 ng/dL, with a sensitivity of 71.43% and a specificity of 85.71%. Multivariate analysis showed that patients with higher values of pretransplant AFP (>16 000 ng/dL) had a significantly higher risk of EFS than those transplanted with lower levels (HR: 10.180; 95% CI: 1.54-66.97; P = .02). Efforts should be made to improve the selection of candidates for LT for unresectable HB, aiming at a better definition of chemoresistance as a risk factor of poor outcomes.

Waiting list outcome of Peld/Meld exceptions: A single-center experience in Argentina.

As PELD/MELD-based allocation policy was adopted in Argentina in 2005, a system of exception points has been in place in order to award increased waitlist priority to those patients whose severity of illness is not captured by the PELD/MELD score. We aimed to investigate the WL outcome of patients with granted PELD/MELD exceptions. A retrospective cohort study was conducted in children under 18 years old. WL outcomes were evaluated using univariable analysis. From 07/2005 to 01/2014, 408 children were listed for LT. There were 304 classified by calculated PELD/MELD. During this time, 85 (30%) PELD/MELD exceptions were granted. In this cohort, 89.4% (76 of 85) were transplanted and 7.1% (6 of 85) died while on the WL. The remaining 3 pts (3.5%) were removed from the WL due to other causes. We compared the impact of PELD/MELD exceptions in those 85 patients to outcomes in 87 non-exception patients with PELD/MELD ≥19 points. Patients with the exception had significantly better access to WL and lower WL mortality. Our data suggest that children listed by PELD/MELD exceptions had an advantage compared to children with CLD with equivalent PELD/MELD listing priorities.