Introduction:
Adenovirus has been implicated as a cause of acute liver failure (ALF) following a global outbreak of adenovirus associated ALF in 2021. In order to understand the association between adenovirus and ALF it is important to know the baseline prevalence of adenovirus (and other childhood viruses) in the population of children undergoing liver transplant for acute and chronic liver disease. Various viruses are known to cause acute hepatitis with or without synthetic liver dysfunction. In 2021 clustered cases of“acute severe hepatitis” and ALF in young children were reported in association with adenovirus infection. For this reason, we have performed viral PCR for adenovirus, EBV, CMV, and HHV-6 on stored liver explant tissue collected as part of an IRB approved liver repository at the Children’s Hospital of Philadelphia. Our objective was to perform retrospective evaluation of prevalence of hepatotropic viruses among children who underwent liver transplant at our center.

Methods:
We studied 33 frozen hepatic explant samples (originally collected between 2004 and 2021 and stored at -80 degrees) which fell into 3 categories; acute liver failure (ALF, n=18; 13 indeterminate, 5 with specific diagnoses), acute on chronic liver failure (ACLF, n=7), and chronic liver disease (CLD, n=8). DNA was extracted via the Qiagen EZ system and accompanying EZ virus mini kit. Viral PCR testing was done using ThermoFischer QuantStudio Real Time PCR using commercially available primers with appropriate positive and negative controls.

Results:
Adenovirus was detected by PCR in a single case of indeterminate ALF transplanted in 2019 (1/18) and in none of the ACLF or CLD cases. CMV was detected in two ALF cases, one indeterminate (not the same as the adenovirus case) and one with bile acid synthesis defect, CMV was not detected in any other group. There were no EBV positive specimens in any group. As expected, HHV-6 was more prevalent, 21 of 33 specimens were positive including 12/13 indeterminate ALF cases; 2/5 specific ALF cases; 2/7 ACL; and 5/8 CLD.

Conclusion:
This retrospective study of the prevalence of common childhood viruses in liver explants provides important baseline information for those studying potential viral etiologies of acute liver failure. HHV-6 was observed in 21/33 (64%) of all liver explants even in stable outpatients with CLD underscoring the high prevalence but non-specific association with acute disease. HHV-6 prevalence did not statistically differ among our study groups.