Relationship Between Viremia and Specific Organ Damage in Ebola Patients: A Cohort Study
Relationship Between Viremia and Specific Organ Damage in Ebola Patients: A Cohort Study
复制标题
DOI：
10.1093/cid/cix704
复制
发表时间：
2018-01-01
影响因子：
11.8
通讯作者：
Ippolito, Giuseppe
中科院分区：
文献类型：
--
作者：
Lanini, Simone;Portella, Gina;Ippolito, Giuseppe
背景埃博拉病毒病的发病机制仍然知之甚少。我们同时测定了常规实验室生物标志物和埃博拉病毒血症，以探讨病毒复制在特定器官损伤中的潜在作用。我们招募了在塞拉利昂的EMERGENCY非政府组织非营利组织埃博拉治疗中心（ONG ONLUS）收治的可检测到埃博拉病毒血症的患者。记录埃博拉病毒血症、丙氨酸氨基转移酶（ALT）、天冬氨酸氨基转移酶（AST）、胆红素、肌酸磷酸激酶（CPK）、乳酸脱氢酶（LDH）、活化凝血酶原时间（aPTT）、国际标准化比值（INR）、肌酐和血尿素氮（BUN）的重复测量。随访患者入院至死亡或出院。100名患者（49名幸存者和51名非幸存者）被纳入分析。未调整的分析比较幸存者和非幸存者提供的证据表明，所有生物标志物均显着高于正常范围，这些异常的程度一般是在非幸存者高于幸存者。多变量混合效应模型为病毒血症水平与ALT、AST、CPK、LDH、aPTT和INR之间的生物梯度（提示在器官损伤中的直接作用）提供了强有力的证据。相反，病毒血症与肌酐、BUN或胆红素之间没有直接的线性关系。这项研究提供了证据，支持埃博拉病毒可能在肌肉损伤和凝血系统失衡中发挥直接作用。我们没有发现强有力的证据表明埃博拉病毒在肾损伤中的直接作用。病毒在肝损伤中的作用尚不清楚，但我们的证据表明，急性严重肝损伤不是埃博拉病毒病的典型特征。
Background. Pathogenesis of Ebola virus disease remains poorly understood. We used concomitant determination of routine laboratory biomarkers and Ebola viremia to explore the potential role of viral replication in specific organ damage.Methods. We recruited patients with detectable Ebola viremia admitted to the EMERGENCY Organizzazione Non Governativa Organizzazione Non Lucrativa di Utilita Sociale (ONG ONLUS) Ebola Treatment Center in Sierra Leone. Repeated measure of Ebola viremia, alanine aminotransferase (ALT), aspartate aminotransferase (AST), bilirubin, creatine phosphokinase (CPK), lactate dehydrogenase (LDH), activated prothrombin time (aPTT), international normalized ratio (INR), creatinine, and blood urea nitrogen (BUN) were recorded. Patients were followed up from admission until death or discharge.Results. One hundred patients (49 survivors and 51 nonsurvivors) were included in the analysis. Unadjusted analysis to compare survivors and nonsurvivors provided evidence that all biomarkers were significantly above the normal range and that the extent of these abnormalities was generally higher in nonsurvivors than in survivors. Multivariable mixed-effects models provided strong evidence for a biological gradient (suggestive of a direct role in organ damage) between the viremia levels and either ALT, AST, CPK LDH, aPTT, and INR. In contrast, no direct linear association was found between viremia and either creatinine, BUN, or bilirubin.Conclusions. This study provides evidence to support that Ebola virus may have a direct role in muscular damage and imbalance of the coagulation system. We did not find strong evidence suggestive of a direct role of Ebola virus in kidney damage. The role of the virus in liver damage remains unclear, but our evidence suggests that acute severe liver injury is not a typical feature of Ebola virus disease.