AUTHOR=Engel Bastian , Görzer Irene , Campos-Murguia Alejandro , Hartleben Björn , Puchhammer-Stöckl Elisabeth , Jaeckel Elmar , Taubert Richard 

TITLE=Association of torque teno virus viremia with liver fibrosis in the first year after liver transplantation

JOURNAL=Frontiers in Immunology

VOLUME=Volume 14 - 2023

YEAR=2023

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2023.1215868

DOI=10.3389/fimmu.2023.1215868

ISSN=1664-3224

ABSTRACT=Torque Teno virus (TTV) replication is controlled by immune status, mirroring degree of immunosuppression after solid organ transplantation. TTV viraemia (TTVv) associated with acute cellular rejection and infection within the first year after liver transplantation (LT). Longterm data on TTV after LT and correlation with graft injury from protocol biopsies are limited.One hundred plasma samples paired with graft biopsies from a prospective single-center biorepository were analyzed. The median time post-LT was 23 months (range: 2-298). TTVv was detectable in 97%. TTVv decreased over time after LT and showed a significant decline from year one to later time points. So, TTVv correlated negatively with histologic liver fibrosis (LAF and Ishak scores) and positively with the overall immunosuppression degree quantified by an immunosuppression score in the first year after LT. There was no association with dosages or trough levels of single immunosuppressants. The pharmacodynamic marker TTVv did not correlate with pharmacokinetic assessments of immunosuppression degree (CNI trough levels or immunosuppressant dosages), our clinical gold standards to guide immunosuppressive therapy. TTVv was independently associated with histologically proven liver fibrosis after LT in the first year after LT in multivariate analysis. Hence, the independent association of histological graft fibrosis with lower TTVv in year one underscores that a pharmacodynamic marker would be preferable to individualize immunosuppression after LT. Yet, high variability of TTVv at the low immunosuppression doses given after the first year precludes TTV as a clinically useful marker after LT in long-term liver transplant recipients.