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.

Changing Etiologies and Prognostic Factors in Pediatric Acute Liver Failure.

After the implementation of universal hepatitis A virus vaccination in Argentina, the outcome of pediatric acute liver failure (PALF) remains unknown. We aimed to identify variables associated with the risk of liver transplantation (LT) or death and to determine the causes and short-term outcomes of PALF in Argentina. We retrospectively included 135 patients with PALF listed for LT between 2007 and 2016. Patients with autoimmune hepatitis (AIH), Wilson's disease (WD), or inborn errors of metabolism (IEM) were classified as PALF-chronic liver disease (CLD), and others were classified as "pure" PALF. A logistic regression model was developed to identify factors independently associated with death or need of LT and risk stratification. The most common etiologies were indeterminate (52%), AIH (23%), WD (6%), and IEM (6%). Overall, transplant-free survival was 35%, whereas 50% of the patients underwent LT and 15% died on the waiting list. The 3-month risk of LT or death was significantly higher among patients with pure PALF compared with PALF-CLD (76.5% versus 42.5%; relative risk, 1.8 [1.3-2.5]; P < 0.001), and 3 risk factors were independently associated with worse outcome: international normalized ratio (INR) ≥3.5 (odds ratio [OR], 3.1; 95% confidence interval [CI], 1.3-7.2]), bilirubin ≥17 mg/dL (OR, 4.4; 95% CI, 1.9-10.3]), and pure PALF (OR, 3.8; 95% CI, 1.6-8.9). Patients were identified by the number of risk factors: Patients with 0, 1, or ≥2 risk factors presented a 3-month risk of worse outcome of 17.6%, 36.6%, and 82%, respectively. In conclusion, although lacking external validation, this simple risk-staging model might help stratify patients with different transplant-free survival rates and may contribute to establishing the optimal timing for LT.

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.

Intrahepatic and peripheral blood phenotypes of natural killer and T cells: differential surface expression of killer cell immunoglobulin-like receptors.

Deep characterization of the frequencies, phenotypes and functionalities of liver and peripheral blood natural killer (NK), natural killer T (NKT) and T cells from healthy individuals is an essential step to further interpret changes in liver diseases. These data indicate that CCR7, a chemokine essential for cell migration through lymphoid organs, is almost absent in liver NK and T cells. CD56bright NK cells, which represent half of liver NK cells, showed lower expression of the inhibitory molecule NKG2A and an increased frequency of the activation marker NKp44. By contrast, a decrease of CD16 expression with a potential decreased capacity to perform antibody-dependent cellular cytotoxicity was the main difference between liver and peripheral blood CD56dim NK cells. Liver T cells with an effector memory or terminally differentiated phenotype showed an increased frequency of MAIT cells,T-cell receptor-γδ (TCR-γδ) T cells and TCR-αß CD8+ cells, with few naive T cells. Most liver NK and T cells expressed the homing markers CD161 and CD244. Liver T cells revealed a unique expression pattern of killer cell immunoglobulin-like receptors (KIR) receptors, with increased degranulation ability and higher secretion of interferon-γ. Hence, the liver possesses a large amount of memory and terminally differentiated CD8+ cells with a unique expression pattern of KIR activating receptors that have a potent functional capacity as well as a reduced amount of CCR7, which are unable to migrate to regional lymph nodes. These results are consistent with previous studies showing that liver T (and also NK) cells likely remain and die in the liver.

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.

Factores de riesgo prequirúrgicos para una colecistectomía laparoscópica difícil / Preoperative risk factors for difficult laparoscopic cholecystectomy

RESUMEN Antecedentes: varios estudios observacionales han identificado factores de riesgo (FR) para una colecistectomía laparoscópica difícil (CLD). Objetivo: identificar los FR preoperatorios para CLD en un hospital público de mediana complejidad. Material y métodos: estudio prospectivo de cohorte transversal. Se analizaron 80 pacientes mayores de 18 años sometidos a colecistectomía laparoscópica, entre enero y diciembre de 2019. Se analizaron las variables: edad, sexo, IMC (índice de masa corporal), litiasis vesicular, pancreatitis aguda, colecistitis aguda o crónica, síndrome de Mirizzi, CPRE dentro del mes, numero de cólicos en el último mes, si presentó al menos un cólico en la última semana, leucocitos, enzimas hepáticas mayores, bilirrubina total, hallazgos de ecografía prequirúrgicos, antecedentes de cirugías abdominales previas. Resultados: la incidencia de CLD fue de 47,5%. La tasa de conversión a cirugía convencional fue del 11,25%, el 100% fueron CLD. Los FR para CLD incluyeron sexo masculino (OR: 4,50, IC 95%:1,60-12,62, p: 0,004), cólico en la semana previa a la cirugía (OR:7,17, IC 95%:1,89-27,23, p: 0,004), paredes engrosadas de la vesícula (OR: 4.90, IC 95%:1,90-12,70, p: 0,001), edema perivesicular (OR: 7,14 IC 95%:1,45-35,13 p: 0,016), la vesícula hidrópica (OR: 4,94, IC 95%:1,44-16,88, p: 0,011) y las cirugías previas (OR: 4.38 IC 95%:1,27-15,10 p: 0,001). En el análisis multivariado vemos que los pacientes de sexo masculino y pacientes con cirugías previas presentaban un riesgo elevado para CLD (OR: 6,63 IC 95%:1,75-25,08 p: 0.005; OR: 11.70 IC 95%:1,48-92,37 p: 0,020). Conclusión: se deben centrar los esfuerzos en identificar los pacientes con sospecha de CLD, pudiendo planificar la cirugía y un equipo quirúrgico experimentado.

ABSTRACT Background: The risk factors (RF) for difficult laparoscopic cholecystectomy (DLC) have been identified in many observational studies. Objective: The aim of this study is to identify the preoperative RF for DLC in a secondary care public hospital. Material and methods: We conducted a prospective cross-sectional cohort study of patients > 18 years undergoing laparoscopic cholecystectomy between January and December 2019. The following variables were analyzed: age, sex, body mass index (BMI), cholelithiasis, acute pancreatitis, acute or chronic cholecystitis, Mirizzi syndrome, ERCP within the previous month, episodes of biliary colic in the last month, presence of at least one colic within one week before surgery, white blood cell count, liver enzymes, total bilirubin, preoperative ultrasound and history of upper abdomen surgery. Results: The rate of DLC was 47.5%. Conversion rate to conventional surgery was 11.25% and 100% were categorized as DLC. The RF for DLC included male sex (OR, 4.50; 95% CI,1.60-12.62; p = 0.004), colic within 1 week before surgery (OR, 7.17; 95% CI,1.89-27.23; p = 0.004), gallbladder wall thickening (OR, 4.90; 95% CI,1.90-12.70; p = 0.001), edema around the gallbladder (OR, 7.14; 95% CI, 1.45-35.13; p = 0.016), hidrops gallbladder (OR, 4.94; 95% CI,1.44-16.88; p = 0.011) and previous surgeries (OR, 4.38; 95% CI, 1.27-15.10; p = 0.001). On multivariate analysis, male sex and previous surgery were associated with higher risk of DLC (OR, 6.63; 95% CI,1.75-25.08; p = 0.005; and OR, 11.70, 95% CI,1.48-92.37; p = 0.020, respectively). Conclusion: Efforts should focus on identifying patients with suspicion of DLC to plan surgery with an experienced surgical team.