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. 2023 Jul 17;7(8):e0175.
doi: 10.1097/HC9.0000000000000175. eCollection 2023 Aug 1.

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

Sarah Kemme  1 , Jennifer D Canniff  2 , Amy G Feldman  3 , Krystle M Garth  2 , Shaobing Li  4 , Zhaoxing Pan  5 , Ronald J Sokol  3 , Adriana Weinberg  2 , Cara L Mack  6
Affiliations

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

Sarah Kemme et al. Hepatol Commun. .

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.

Trial registration: ClinicalTrials.gov NCT00061828.

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Conflict of interest statement

Ronald J. Sokol consults for Alexion and advises Mirum and Albireo. Adriana Weinburg advises and received grants from GlaxoSmithKline and Merck. She advises Seqirus. The remaining authors have no conflicts to report.

Figures

FIGURE 1
FIGURE 1
Kaplan-Meier analysis showing the proportion of participants with biliary atresia with native liver survival in CMV positive versus CMV negative groups, including (A) any age at HPE, (B) only those with HPE at younger than 60 days of life, and (C) only those with HPE at 60 days of life or older. No differences between CMV positive and negative groups were found. Abbreviations: CMV, cytomegalovirus; HPE, hepatic portoenterostomy.
FIGURE 2
FIGURE 2
Cox proportional hazard regression analysis modeling of native liver survival in (A) CMV positive versus CMV negative participants, adjusted for age at HPE, and (B) participants with HPE at 1.4 versus 1.9 versus 2.4 months of age, adjusted for CMV status. Abbreviations: CMV, cytomegalovirus; HPE, hepatic portoenterostomy.
FIGURE 3
FIGURE 3
Gray’s competing risk analysis with liver transplantation as a competing risk showing CIF of death in participants with biliary atresia before liver transplant in CMV positive versus CMV negative groups, including (A) any age of HPE, (B) only those with HPE at younger than 60 days of life, and (C) only those with HPE at 60 days of life or older. Abbreviations: CIF, cumulative incidence function; CMV, cytomegalovirus; HPE, hepatic portoenterostomy.
FIGURE 4
FIGURE 4
Fine-Gray competing risk subdistribution hazard modeling predicted values of CIF of death until 40 months post- HPE in (A) CMV positive versus CMV negative participants, adjusted for age at HPE, and (B) participants with HPE at 1.4 versus 1.9 versus 2.4 months of age, adjusted for CMV status. Abbreviations: CIF, cumulative incidence function; CMV, cytomegalovirus; HPE, hepatic portoenterostomy.
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References

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