After the implementation of universal hepatitis A virus vaccination inArgentina, 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. Liver Transplantation 26 268-275 2020 AASLD.

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. CD56 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 CD56 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-αβ 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.

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.

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.

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.