Cytomegalovirus in biliary atresia is associated with increased pretransplant death, but not decreased native liver survival

Author:

Kemme Sarah1ORCID,Canniff Jennifer D.2,Feldman Amy G.3ORCID,Garth Krystle M.2,Li Shaobing4,Pan Zhaoxing5,Sokol Ronald J.3ORCID,Weinberg Adriana2ORCID,Mack Cara L.6ORCID

Affiliation:

1. D.Brent Polk Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Monroe Carrell Jr. Children’s Hospital at Vanderbilt, Nashville, Tennessee, USA

2. Department of Pediatrics, Medicine, and Pathology, University of Colorado, Aurora, Colorado, USA

3. Digestive Health Institute, Section of Pediatric Gastroenterology, Hepatology and Nutrition, University of Colorado School of Medicine and Children’s Hospital Colorado, Aurora, Colorado, USA

4. Pediatric Infectious Diseases, University of Colorado School of Medicine, Aurora, Colorado, USA

5. Department of Pediatrics, Research Institute, Children’s Hospital Colorado, University of Colorado School of Medicine, Aurora, Colorado, USA

6. Division of Pediatric Gastroenterology, Department of Pediatrics, Hepatology & Nutrition, Medical College of Wisconsin, Children’s Wisconsin, Milwaukee, Wisconsin, USA

Abstract

Background: Biliary atresia (BA) is likely caused by a common phenotypic response to various triggers; one proposed trigger, cytomegalovirus (CMV), may lead to worse outcomes. The aim of this study was to determine the severity of disease and pretransplant outcomes of infants with BA, who have evidence of CMV (CMV+) at diagnosis compared with CMV-negative (CMV−) infants. Methods: The study used data and biospecimens from the Childhood Liver Disease Research Network PROBE study of cholestatic infants. Plasma obtained at the time of hepatic portoenterostomy (HPE) of 249 infants with BA was tested for CMV by DNA-PCR and CMV-IgM. Comparisons between CMV+ and CMV− infants were made using Wilcoxon rank sum, Student t test, chi-square, or Fisher exact test. Native liver survival (NLS) outcomes were analyzed using Kaplan-Meier and Cox regression adjusting for age at HPE; pretransplant patient survival outcomes were analyzed using a competing risk model and adjusting for age at HPE. Results: CMV+ infants (n = 29, 12%) underwent HPE later (67.8±13.6 d vs. 55.1±18.5 d, p = 0.0005) and had higher baseline alkaline phosphatase and aminotransferases. There was no difference between groups in jaundice clearance or NLS. The subdistribution HR of pretransplant death for CMV+ infants adjusted for age at HPE was 3.8 (p = 0.034). Conclusions: CMV infection at the time of HPE in infants with BA is not associated with worse NLS despite the association with worse liver injury, older age at HPE, and increased risk of pretransplant death adjusted for age at HPE. Continued evaluation of the consequences of CMV infection and the effects of antiviral treatment should be explored.

Publisher

Ovid Technologies (Wolters Kluwer Health)

Subject

Hepatology

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