Department for Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany; Integrierte Forschungs- und Behandlungszentrum Transplantation (IFB-Tx), Hannover Medical School, Hannover, Germany.
Institute of Virology, Hannover Medical School, Hannover, Germany.
J Hepatol. 2012 May;56(5):1063-1069. doi: 10.1016/j.jhep.2011.12.017. Epub 2012 Jan 13.
BACKGROUND & AIMS: In liver transplant recipients with graft hepatitis, the relevance of herpesviruses is not well defined.
Viral loads of CMV, EBV, and HHV-6 were determined in blood and liver biopsies of 170 liver transplant recipients with graft hepatitis by quantitative PCR.
HHV-6-, CMV-, and EBV-DNA were detected in 58%, 14%, and 44% of the biopsies, respectively, with coinfections in 34%. High intrahepatic HHV-6 DNA levels (>75th percentile, 11.27 copies/1000 cells) and detection of HHV-6 DNAemia were significantly associated with decreased graft survival after diagnosis of graft hepatitis (p=0.014 and p=0.003, respectively, median follow-up was 23.8 months). Multivariate analysis confirmed high intrahepatic HHV-6 loads as an independent factor associated with reduced graft survival (adjusted hazard ratio 2.61, 95%confidence interval 1.16-5.87). Low concentrations of HHV6 DNA in the liver, indicating latent infection, did not influence graft survival. Neither CMV nor EBV (qualitative detection and high virus loads) nor acute rejection (according to the BANFF score) affected graft survival. However, patients had been treated for CMV reactivations and acute rejections in this retrospective study. High age and high bilirubin levels were the other independent factors associated with reduced graft survival (adjusted hazard ratio 3.56CI 1.52-8.34 and 3.23CI 1.50-6.96, respectively).
High intrahepatic HHV-6-DNA levels are associated with decreased graft survival in liver transplant recipients with graft hepatitis. The significance of HHV-6 as potential etiology of graft hepatitis needs further evaluation.
在发生移植物肝炎的肝移植受者中，疱疹病毒的相关性尚未明确。
采用实时定量 PCR 法检测 170 例发生移植物肝炎的肝移植受者的血和肝组织中 CMV、EBV 和 HHV-6 的病毒载量。
分别有 58%、14%和 44%的肝组织中检测到 HHV-6、CMV 和 EBV-DNA，34%的肝组织中存在混合感染。肝内 HHV-6 DNA 水平较高（>75 百分位值，11.27 拷贝/1000 个细胞）和 HHV-6 血症的检出与诊断为移植物肝炎后的移植物存活率下降显著相关（p=0.014 和 p=0.003，中位随访时间为 23.8 个月）。多变量分析证实，肝内 HHV-6 负荷较高是与移植物存活率下降相关的独立因素（调整后的危险比为 2.61，95%置信区间为 1.16-5.87）。提示潜伏感染的低水平肝内 HHV-6 DNA 并不会影响移植物存活率。CMV 和 EBV（定性检测和高病毒载量）以及急性排斥反应（根据 BANFF 评分）均未影响移植物存活率。然而，在这项回顾性研究中，患者曾因 CMV 再激活和急性排斥反应而接受治疗。高龄和高胆红素水平也是与移植物存活率下降相关的其他独立因素（调整后的危险比分别为 3.56CI 1.52-8.34 和 3.23CI 1.50-6.96）。
肝内 HHV-6 DNA 水平较高与发生移植物肝炎的肝移植受者的移植物存活率下降相关。HHV-6 作为移植物肝炎潜在病因的意义需要进一步评估。
