National Institute for Infectious Diseases "Lazzaro Spallanzani," Istituto di Ricovero e Cura a Carattere Scientifico, Rome, Italy.
International Public Health Crisis Group, Milan, Italy.
Clin Infect Dis. 2018 Jan 6;66(1):36-44. doi: 10.1093/cid/cix704.
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.
We recruited patients with detectable Ebola viremia admitted to the EMERGENCY Organizzazione Non Governativa Organizzazione Non Lucrativa di Utilità 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.
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.
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.
埃博拉病毒病的发病机制仍不清楚。我们同时测定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 非营利组织非政府组织非政府组织（ONG ONLUS）埃博拉治疗中心接受检测到埃博拉病毒血症的患者。反复测量埃博拉病毒血症、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）、活化部分凝血活酶时间（aPTT）、国际标准化比值（INR）、肌酐和血尿素氮（BUN）。患者从入院到死亡或出院进行随访。
100 例患者（49 例存活和 51 例死亡）纳入分析。对幸存者和非幸存者进行未调整的分析比较，有证据表明所有生物标志物均明显高于正常范围，且非幸存者的这些异常程度通常高于幸存者。多变量混合效应模型提供了强有力的证据表明，病毒血症水平与 ALT、AST、CPK LDH、aPTT 和 INR 之间存在生物学梯度（提示对器官损伤有直接作用）。相比之下，在病毒血症与肌酐、BUN 或胆红素之间未发现直接线性关联。
本研究提供的证据支持埃博拉病毒可能在肌肉损伤和凝血系统失衡中具有直接作用。我们没有发现强有力的证据表明埃博拉病毒在肾脏损伤中有直接作用。病毒在肝脏损伤中的作用仍不清楚，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。
