Noelle Ebel, MD

Abstract

Increased mortality risk due to severe acute respiratory syndrome coronavirus-2 (SARS-CoV2) infection in adults with native liver disease (LD) and liver transplant (LT) is associated with advanced age and comorbid conditions. We aim to report outcomes for children with LD and LT enrolled in the NASPGHAN/SPLIT SARS-CoV2 registry.In this multicenter observational cohort study, we collected data from 91 patients <21years (LD 44, LT 47) with laboratory-confirmed SARS-CoV2 infection between April 21 and September 17, 2020.Patients with LD were more likely to require admission (70% vs 43% LT, p=0.007) and pediatric intensive care unit (PICU) management (32% vs 4% LT, p=0.001). Seven LD patients required mechanical ventilation (MV) and 2 patients died; no patients in the LT cohort died or required MV. Four LD patients presented in pediatric acute liver failure (PALF), 2 with concurrent multisystem inflammatory syndrome in children (MIS-C); all recovered without LT. Two LD patients had MIS-C alone and one patient died. Bivariable logistic-regression analysis found that patients with non-alcoholic fatty liver disease (NAFLD) (OR 5.6, p=0.02) and LD (OR 6.1, p=0.01, vs LT) had higher odds of severe disease (PICU, vasopressor support, MV, renal replacement therapy or death).Although not directly comparable, LT recipients had lower odds of severe SARS-CoV2 infection (vs LD), despite immunosuppression burden. NAFLD patients reported to the registry had higher odds of severe SARS-CoV2 disease. Future controlled studies are needed to evaluate effective treatments and further stratify LD and LT patients with SARS-CoV2 infection.

View details for DOI 10.1097/MPG.0000000000003077

View details for PubMedID 33605666

Abstract

OBJECTIVE: To evaluate risk factors for hepatic artery thrombosis (HAT) and examine the long-term outcomes of graft and patient survival following HAT in pediatric recipients of liver transplantation.STUDY DESIGN: Utilizing multicenter data from the Society of Pediatric Liver Transplantation (SPLIT), Kaplan-Meier and Cox regression analyses were performed on first-time pediatric (aged <18 years) liver transplant recipients (n=3801) in the United States and Canada between 1995 to 2016.RESULTS: Of children undergoing their first liver transplantation, 7.4% developed HAT within the first 90 days of transplantation and of those who were re-transplanted, 20.7% developed recurrent HAT. Prolonged warm ischemia times increased the odds of developing HAT (OR 1.11, p=0.02). Adolescents aged 11-17 years (OR 0.53, p=0.03) and recipients with split, reduced or living donor grafts had decreased odds of HAT (OR 0.59, P < .001 compared with whole grafts). Fifty percent of children who developed HAT developed graft failure within the first 90 days of transplantation (AHR 11.87, 95% CI 9.02,15.62) and had a significantly higher post-transplant mortality within the first 90 days of transplantation (AHR 6.18, 95% CI 4.01,9.53).CONCLUSIONS: These data from an international registry demonstrate poorer long-term graft and patient survival in pediatric recipients whose post-transplant course is complicated by HAT. Notably, recipients of technical variant grafts had lower odds of HAT compared with whole liver grafts.

View details for DOI 10.1016/j.jpeds.2020.06.053

View details for PubMedID 32585237

Abstract

To assess outcomes in a large cohort of patients with Alagille Syndrome (ALGS) who underwent pulmonary artery reconstruction surgery for complex PA disease.Patients with ALGS who underwent PA reconstruction surgery at Lucile Packard Children's Hospital Stanford were reviewed. Patients were examined as an overall cohort and based on the primary cardiovascular diagnosis: severe isolated branch PA stenosis, tetralogy of Fallot (TOF) without major aortopulmonary collateral arteries (MAPCAs), or TOF with MAPCAs RESULTS: Fifty-one patients with ALGS underwent PA surgery at our center: 22 with severe branch PA stenosis, 9 with TOF without MAPCAs, and 20 with TOF and MAPCAs. Forty-one patients (80%) achieved a complete repair. Five of the patients with TOF with MAPCAs (25%) had a complete repair at the first surgery, compared with 8 (89%) and 19 (86%) with TOF without MAPCAs and isolated branch PA stenosis, respectively. At a median follow-up of 1.7 years after the first surgery, 39 patients (76%) were alive, 36 with a complete repair and a median PA:aortic systolic pressure ratio of 0.38. Nine patients (18%), 8 with isolated branch PA stenosis, underwent liver transplantation.Most patients with ALGS and complex PA disease can undergo complete repair with low postoperative right ventricular pressure. Patients with TOF/MAPCAs had the worst outcome, with higher mortality and more frequent PA interventions compared with patients with TOF without MAPCAs or isolated branch PA stenosis. Complex PA disease is not a contraindication to liver transplantation in patients with ALGS.

View details for DOI 10.1016/j.jpeds.2020.09.053

View details for PubMedID 32980376

Abstract

In adults, elevated hepatic venous pressure gradients (HVPGs) are correlated with the degree of liver fibrosis on histopathology and predict worse outcomes including variceal bleeding and death. We aimed to examine the association between HVPG measurements, histopathologic findings, and clinical indicators of portal hypertension in children.Utilizing retrospective data from 2 pediatric centers between 2006 and 2015, we identified children who underwent simultaneous HVPG measurement and transjugular liver biopsy. Medical charts were reviewed for histopathology, imaging, endoscopic, and clinical data.Forty-one children (median age 11 years) were included in the analysis with diagnoses of acute hepatitis (n=15), chronic liver disease (n=12), hepatic noncirrhotic portal hypertension (n=4), acute liver failure (n=3), and nonhepatic causes of portal hypertension (n=7). Elevated mean HVPG measurements were found in children with acute liver failure (10 mmHg, range 4-12) and chronic liver disease (7 mmHg, range 1-12). HVPG measurements did not correlate with the histological severity of fibrosis (=0.23, P=0.14) or portal inflammation (=0.24, P=0.29), and no difference was found in HVPG when comparing children with and without a history of variceal bleeding (P=0.43).HVPG measurements do not correlate significantly with the degree of hepatic fibrosis on biopsy. Furthermore, HVPG measurements are not associated with the presence of varices or history of variceal bleeding, suggesting the possibility of intrahepatic shunting in children with advanced liver disease. Therefore, unlike in adults, HVPG measurements may not accurately predict children who are at risk of complications from portal hypertension.

View details for DOI 10.1097/MPG.0000000000002327

View details for PubMedID 30921261

Abstract

We evaluated liver transplantation waitlist and posttransplantation outcomes in those aged 18 to 24 years compared with both younger (0-17 years) and older (25-34 years) registrants and recipients.Using national data from the United Network for Organ Sharing, competing risk, Cox regression and Kaplan-Meier analyses were performed on first-time liver transplant registrants (n = 13 979) and recipients (n = 8718) ages 0 to 34 years between 2002 and 2015.Nonstatus 1A registrants, registrants aged 0 to 17 and 25 to 34 years were less likely to experience dropout from the waiting list compared with those aged 18 to 24 years (adjusted hazard ratio, 0-5 years = 0.36; 6-11 = 0.29; 12-17 = 0.48; 18-24 = 1.00; 25-34 = 0.82). Although there was no difference in risk of graft failure across all age groups, both younger and older age groups had significantly lower risk of posttransplant mortality compared with those aged 18 to 24 years (adjusted hazard ratio, for 0-5 years = 0.53, 6-11 = 0.48, 12-17 = 0.70, 18-24 = 1.00, 25-34 = 0.77). This may be related to lower likelihood of retransplantation after graft failure in those aged 18 to 24 years.This national registry study demonstrates for the first time poorer waitlist and postliver transplant outcomes in young adults ages 18 to 24 years at the time of listing and transplantation compared to older and younger age groups. Given the potential survival benefit in transplanting young adults and the shortage of solid organs for transplant, future studies are critical to identify and target modifiable risk factors to improve waitlist and long-term posttransplant outcomes in 18- to 24-year-old registrants and recipients.

View details for DOI 10.1097/TP.0000000000001689

View details for PubMedID 28230640

View details for PubMedCentralID PMC5481466