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).
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David E Kleiner
Hepatitis C virus/HCV-infected subjects
Hepatic activity index
Prothrombin time international normalized ratio
Model for end-stage liver disease
Platelet-derived growth factor A
Platelet-derived growth factor B
Transforming growth factor beta isoform 1
Epidermal growth factor
Vascular endothelial growth factor
Intercellular adhesion molecule
Vascular cell adhesion molecule
Vascular injury marker
Chronic liver disease
David E. Kleiner
Direct acting antiviral therapy
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We thank the patients, fellows, nurses, all staff, and institutional review board that assisted in the study.
This work was supported by the Intramural Research Program, National Institute of Diabetes and Digestive and Kidney Diseases.
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Ali, R.O., Moon, M.S., Townsend, E.C. et al. Exploring the Link Between Platelet Numbers and Vascular Homeostasis Across Early and Late Stages of Fibrosis in Hepatitis C. Dig Dis Sci 65, 524–533 (2020). https://doi.org/10.1007/s10620-019-05760-x