Torque Teno Virus Is Associated With the State of Immune Suppression Early After Liver Transplantation.

Abstract

The development of noninvasive biomarkers that reflect the state of immunosuppression (IS) remains an unmet need in liver transplantation (LT). Torque Teno virus (TTV) is a highly prevalent, nonpathogenic DNA virus whose plasma levels may be associated with the immune status of the host. The aim of this study was to assess the role of TTV as a biomarker of IS in LT recipients. TTV DNA in plasma was quantified by real-time polymerase chain reaction at different time points during the first year after transplant in a prospectively followed cohort of 63 de novo LT recipients, and any correlation between TTV DNA and biopsy-proven acute cellular rejection (ACR) and opportunistic infections was then evaluated. In addition, TTV DNA was studied in 10 longterm LT recipients in monotherapy with tacrolimus, 10 tolerant recipients, and 10 healthy controls. TTV was detected in the plasma of all patients. Among the 63 LT recipients, 20 episodes of ACR were diagnosed, and there were 28 opportunistic infections, 26 of them being cytomegalovirus (CMV) infections. TTV viremia was significantly lower during ACR (4.41 versus 5.95 log10 copies/mL; P = 0.002) and significantly higher during CMV infections (5.79 versus 6.59 log10 copies/mL; P = 0.009). The area under the receiver operating characteristic curve of TTV viral load for the diagnosis of moderate ACR was 0.869, with a sensitivity and negative predictive value of 100%, respectively, for a cutoff point of 4.75 log10 copies/mL. There were no statistically significant differences in TTV DNA in either longterm or tolerant patients and healthy controls. In conclusion, plasma TTV DNA levels are associated with immune-related events after LT and could constitute a potential biomarker of the state of IS during the first months after transplant.