Department of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology, Hannover Medical School, Hannover, Germany.
Center for Virology, Medical University of Vienna, Vienna, Austria.
Front Immunol. 2023 Jul 18;14:1215868. doi: 10.3389/fimmu.2023.1215868. eCollection 2023.
Torque teno virus (TTV) replication is controlled by immune status, mirroring a degree of immunosuppression after solid organ transplantation. TTV viraemia (TTVv) was associated with acute cellular rejection and infection within the first year after liver transplantation (LT). Long-term 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 1 to later time points. Hence, TTVv correlated negatively with histologic liver fibrosis (liver allograft fibrosis 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 [calcineurin inhibitor (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.
The independent association of histological graft fibrosis with lower TTVv in year 1 underscores that a pharmacodynamic marker would be preferable to individualize immunosuppression after LT. However, a high variability of TTVv at the low immunosuppression doses given after the first year precludes TTV as a clinically useful marker after LT in the long-term liver transplant recipients.
Torque teno 病毒 (TTV) 的复制受免疫状态控制，反映出实体器官移植后一定程度的免疫抑制。TTV 病毒血症 (TTVv) 与肝移植 (LT) 后 1 年内的急性细胞排斥反应和感染有关。LT 后 TTV 的长期数据以及与方案活检中移植物损伤的相关性有限。
分析了来自前瞻性单中心生物标本库的 100 个血浆样本和移植活检样本。
LT 后中位时间为 23 个月（范围，2-298）。97%的样本可检测到 TTVv。LT 后 TTVv 随时间下降，从第 1 年到后期时间点呈显著下降趋势。因此，TTVv 与组织学肝纤维化（肝移植纤维化和 Ishak 评分）呈负相关，与 LT 后第 1 年通过免疫抑制评分量化的整体免疫抑制程度呈正相关。TTVv 与单种免疫抑制剂的剂量或谷浓度均无相关性。药效标志物 TTVv 与免疫抑制程度的药代动力学评估（钙调神经磷酸酶抑制剂 (CNI) 谷浓度或免疫抑制剂剂量）无关，而后者是指导免疫抑制治疗的我们的临床金标准。在多变量分析中，TTVv 在 LT 后第 1 年与组织学证实的肝纤维化独立相关。
在 LT 后第 1 年，组织学供体纤维化与较低的 TTVv 独立相关，这强调了药效标志物在 LT 后个体化免疫抑制方面将更为理想。然而，在第 1 年后给予的低免疫抑制剂量下，TTVv 的高度变异性排除了 TTV 作为 LT 后长期肝移植受者的临床有用标志物。
