Translational Hepatology Section, Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Building 10, Room 9B16, 10 Center Dr. MSC 1800, Bethesda, MD, 20892-1800, USA.
Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Dig Dis Sci. 2020 Feb;65(2):524-533. doi: 10.1007/s10620-019-05760-x. Epub 2019 Aug 12.
Thrombocytopenia is a hallmark of advanced liver disease. Platelets, growth factors (GFs), and vascular integrity are closely linked factors in disease pathogenesis, and their relationship, particularly in early disease stages, is not entirely understood. The aim was to compare circulating platelets, growth factors, and vascular injury markers (VIMs) in hepatitis C-infected (HCV) patients with early fibrosis and cirrhosis.
Retrospective evaluation of serum GFs and VIMs by ELISA were evaluated from twenty-six HCV patients. Analytes from an earlier time-point were correlated with MELD at a later time-point.
Platelets and GFs decreased, and VIMs increased with fibrosis. Platelets correlated positively with PDGF-AA, PDGF-BB, TGFB1, EGF, and P-selectin, and negatively with ICAM-3 and VCAM-1. P-selectin showed no correlations with VIMs but positively correlated with PDGF-AA, PDGF-BB, TGFB1, and EGF. Soluble VCAM-1 and ICAM-3 were linked to increasing fibrosis, liver enzymes, and synthetic dysfunction. Higher VCAM-1 and ICAM-3 and lower P-selectin at an earlier time-point were linked to higher MELD score at a later time-point.
In chronic HCV, progressive decline in platelets and growth factors with fibrosis and their associations suggest that platelets are an important source of circulating GFs and influence GF decline with fibrosis. Enhanced markers of vascular injury in patients with early fibrosis suggest an earlier onset of endothelial dysfunction preceding cirrhosis. Associations of VIMs with platelets suggest a critical link between platelets and vascular homeostasis. Circulating markers of vascular injury may not only have prognostic importance but emphasize the role of vascular dysfunction in liver disease pathogenesis (NCT00001971).
血小板减少症是晚期肝病的标志。血小板、生长因子（GFs）和血管完整性是疾病发病机制中密切相关的因素，它们之间的关系，尤其是在早期疾病阶段，尚未完全阐明。本研究旨在比较丙型肝炎（HCV）感染患者早期纤维化和肝硬化患者循环血小板、生长因子和血管损伤标志物（VIMs）的水平。
通过 ELISA 法对 26 例 HCV 患者的血清 GFs 和 VIMs 进行回顾性评估。对较早时间点的分析物与较晚时间点的 MELD 进行相关性分析。
随着纤维化的进展，血小板和 GFs 减少，VIMs 增加。血小板与 PDGF-AA、PDGF-BB、TGFB1、EGF 和 P-选择素呈正相关，与 ICAM-3 和 VCAM-1 呈负相关。P-选择素与 VIMs 无相关性，但与 PDGF-AA、PDGF-BB、TGFB1 和 EGF 呈正相关。可溶性 VCAM-1 和 ICAM-3 与纤维化、肝酶和合成功能障碍的增加有关。早期较高的 VCAM-1 和 ICAM-3 以及较低的 P-选择素与晚期较高的 MELD 评分相关。
在慢性 HCV 中，随着纤维化的进展，血小板和生长因子逐渐减少，它们之间的相关性提示血小板是循环 GFs 的重要来源，并影响 GF 随纤维化的减少。早期纤维化患者血管损伤标志物的增加提示内皮功能障碍在肝硬化前更早发生。VIMs 与血小板的相关性提示血小板与血管稳态之间存在关键联系。循环血管损伤标志物不仅具有预后意义，而且强调了血管功能障碍在肝病发病机制中的作用（NCT00001971）。
