Low Torque Teno Virus Load Is Associated With Fibrosis in Protocol Biopsies Following Liver Transplantation: A Nordic Multicenter Cohort Study

Graft inflammation and fibrosis are associated with progressive fibrosis and potential graft loss after liver transplantation, but diagnosis relies on invasive biopsies. Torque teno virus (TTV) may be a noninvasive marker of functional immunity, however its association with these changes remains unclear. In this Nordic multicenter cohort study, plasma samples collected with biopsies were analyzed for TTV load, and biopsies were scored for inflammation and fibrosis. Associations and performance of TTV versus tacrolimus were evaluated using logistic regression and ROC curves. TTV was categorized using the Youden Index. Among 287 liver transplant recipients, median age was 55, mean TTV load 5 log 10 copies/mL and median time from transplantation to TTV measurement 12 months. Low TTV load was associated with higher odds of fibrosis (aOR 2.96 [95% CI 1.40–6.25], adjusted for time since transplantation). Compared with tacrolimus, TTV load remained associated with fibrosis (2.64 [1.19–5.85]), whereas tacrolimus did not (1.16 [0.95–1.42]). The model including both markers had the highest AUC (0.69 [0.60–0.78]). At the optimal threshold, TTV demonstrated 64% sensitivity and specificity, positive predictive value 20% and negative predictive value 93%. TTV load was not significantly associated with inflammation. In conclusion, TTV load may support risk‐stratified biopsy strategies, requiring external validation.