Liver Transplant Unit, Liver Unit, Hospital Clínic de Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, University of Barcelona, Barcelona, Spain.
Liver Unit, Hospital Clínic de Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, University of Barcelona, Barcelona, Spain.
Liver Transpl. 2019 Feb;25(2):302-310. doi: 10.1002/lt.25374.
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 log copies/mL; P = 0.002) and significantly higher during CMV infections (5.79 versus 6.59 log 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 log 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.
在肝移植（LT）中，开发反映免疫抑制（IS）状态的非侵入性生物标志物仍然是未满足的需求。Torque Teno 病毒（TTV）是一种高度流行的非致病性 DNA 病毒，其血浆水平可能与宿主的免疫状态相关。本研究旨在评估 TTV 作为 LT 受者 IS 生物标志物的作用。在一个前瞻性随访的 63 例新诊断 LT 受者队列中，在移植后第 1 年内的不同时间点通过实时聚合酶链反应定量检测血浆中的 TTV DNA，并评估 TTV DNA 与活检证实的急性细胞排斥（ACR）和机会性感染之间的任何相关性。此外，还在 10 例接受他克莫司单药治疗的长期 LT 受者、10 例耐受受者和 10 例健康对照者中研究了 TTV DNA。所有患者的血浆中均检测到 TTV。在 63 例 LT 受者中，诊断出 20 例 ACR 发作，发生 28 例机会性感染，其中 26 例为巨细胞病毒（CMV）感染。在 ACR 期间，TTV 病毒血症显著降低（4.41 与 5.95 log 拷贝/mL；P = 0.002），在 CMV 感染期间显著升高（5.79 与 6.59 log 拷贝/mL；P = 0.009）。TTV 病毒载量对中度 ACR 的诊断的受试者工作特征曲线下面积为 0.869，截断值为 4.75 log 拷贝/mL 时，灵敏度和阴性预测值分别为 100%。在长期或耐受患者和健康对照者中，TTV DNA 无统计学差异。总之，LT 后血浆 TTV DNA 水平与免疫相关事件相关，可能成为移植后最初几个月 IS 状态的潜在生物标志物。
