Department of Pediatrics, Section of Pediatric Gastroenterology, Texas Children's Hospital, Baylor College of Medicine, Houston, Texas, USA.
Department of Microbiology and Immunology, Tulane University School of Medicine, New Orleans, Louisiana, USA.
J Pediatric Infect Dis Soc. 2021 May 28;10(5):599-606. doi: 10.1093/jpids/piaa166.
Distinctions between HHV-6 primary infection in seronegative patients and HHV-6 reactivation in seropositive patients remains largely undescribed in pediatric liver transplant (LT) recipients.
We implemented pretransplant serology testing of HHV-6 in a large pediatric hospital and retrospectively assessed the incidence, manifestations and outcomes of HHV-6 infections over a 3-year period.
Among 101 pediatric LT recipients, 96 had pretransplant HHV-6 serologies; 34 (35.4%) were seronegative and 62 (64.6%) seropositive. Posttransplantation, 8/25 (32%) seronegative patients had HHV-6 DNAemia (primary infection) compared to 2/48 (4%) seropositive patients (p=0.002). Compared to seropositive patients, seronegative patients with HHV-6 DNAemia were younger, and had symptoms of fever and/or elevated aminotransferases in association with higher viral loads, in the first month post-transplant. More than 90% of seronegative patients and 77.8% of seropositive patients had HHV-6 detected by PCR in liver biopsy obtained for concerns of allograft rejection, but most had no detectable concomitant DNAemia. Active replication of virus in the liver was confirmed by in situ hybridization in select cases. While HHV-6 infection occurred among patients on prophylaxis doses of antivirals for CMV, HHV-6 DNAemia and presenting symptoms resolved on treatment doses.
HHV-6 DNA-emia occurred more frequently in seronegative pediatric LT recipients, usually in the early posttransplant period, and was subsequently detected in allograft biopsies. HHV-6 cannot be ruled out as a cause of hepatitis in the absence of allograft tissue testing and specialized virological assays, as HHV-6 may disrupt local allograft immune homeostasis while evading traditional screening methods using blood or plasma. The assessment of pre-transplant HHV-6 serological status may be important for risk stratification and post-transplant management of pediatric LT recipients.
在血清阴性的儿科肝移植（LT）受者中，HHV-6 原发性感染与 HHV-6 再激活之间的区别在很大程度上仍未得到描述。
我们在一家大型儿科医院实施了 HHV-6 的移植前血清学检测，并回顾性评估了 3 年内 HHV-6 感染的发生率、表现和结果。
在 101 名儿科 LT 受者中，96 名有移植前 HHV-6 血清学检测结果；34 名（35.4%）血清阴性，62 名（64.6%）血清阳性。移植后，25 名血清阴性患者中有 8 名（32%）有 HHV-6 DNA 血症（原发性感染），而 48 名血清阳性患者中有 2 名（4%）（p=0.002）。与血清阳性患者相比，血清阴性、有 HHV-6 DNA 血症的患者年龄较小，在移植后第一个月伴有发热和/或氨基转移酶升高，病毒载量较高。超过 90%的血清阴性患者和 77.8%的血清阳性患者在因移植物排斥而进行的肝活检中通过 PCR 检测到 HHV-6，但大多数患者没有检测到同时存在的 DNA 血症。在选择的病例中，通过原位杂交证实了病毒在肝脏中的活跃复制。虽然 HHV-6 感染发生在接受 CMV 抗病毒预防剂量治疗的患者中，但在接受治疗剂量治疗后，HHV-6 DNA 血症和出现的症状得到了缓解。
HHV-6 DNA 血症在血清阴性的儿科 LT 受者中更为常见，通常发生在移植后早期，随后在移植物活检中检测到。在没有移植物组织检测和专门的病毒学检测的情况下，不能排除 HHV-6 是肝炎的原因，因为 HHV-6 可能破坏局部移植物免疫平衡，同时逃避使用血液或血浆的传统筛查方法。评估移植前 HHV-6 血清学状态可能对儿科 LT 受者的风险分层和移植后管理很重要。
