Exploring the Link Between Platelet Numbers and Vascular Homeostasis Across Early and Late Stages of Fibrosis in Hepatitis C

Dig Dis Sci. 2020 Feb;65(2):524-533. doi: 10.1007/s10620-019-05760-x. Epub 2019 Aug 12.

Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusion: 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).

Keywords: Growth factors; Hepatitis C virus (HCV); Platelets; Vascular injury.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Adult
  • Antigens, CD / blood
  • Becaplermin / blood
  • Biomarkers
  • Cell Adhesion Molecules / blood
  • Disease Progression
  • End Stage Liver Disease / blood
  • End Stage Liver Disease / metabolism
  • Endothelial Growth Factors / blood
  • Endothelium, Vascular / metabolism
  • Endothelium, Vascular / physiopathology*
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Hepatitis C, Chronic / blood*
  • Hepatitis C, Chronic / complications
  • Hepatitis C, Chronic / metabolism
  • Homeostasis
  • Humans
  • Liver Cirrhosis / blood*
  • Liver Cirrhosis / etiology
  • Longitudinal Studies
  • Male
  • Middle Aged
  • P-Selectin / blood
  • Platelet Count
  • Platelet-Derived Growth Factor / metabolism
  • Retrospective Studies
  • Severity of Illness Index
  • Thrombocytopenia / blood*
  • Thrombocytopenia / etiology
  • Thrombocytopenia / metabolism
  • Transforming Growth Factor beta1 / blood
  • Vascular Cell Adhesion Molecule-1 / blood

Substances

  • Antigens, CD
  • Biomarkers
  • Cell Adhesion Molecules
  • Endothelial Growth Factors
  • ICAM3 protein, human
  • P-Selectin
  • Platelet-Derived Growth Factor
  • TGFB1 protein, human
  • Transforming Growth Factor beta1
  • Vascular Cell Adhesion Molecule-1
  • platelet-derived growth factor A
  • Becaplermin

Associated data

  • ClinicalTrials.gov/NCT00001971