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

  • Rabab O. AliEmail author
  • Mi Sun Moon
  • Elizabeth C. Townsend
  • Kareen Hill
  • Grace Y. Zhang
  • Alyson Bradshaw
  • Hannah Guan
  • Destanee Hamilton
  • David E. Kleiner
  • Sungyoung Auh
  • Christopher Koh
  • Theo HellerEmail author
Original Article

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

Hepatitis C virus (HCV) Platelets Growth factors Vascular injury 

Abbreviations

ALP

Alkaline phosphatase

ALT

Alanine aminotransferase

AST

Aspartate aminotransferase

DEK

David E Kleiner

HCV

Hepatitis C virus/HCV-infected subjects

IshF

Ishak fibrosis

HAI

Hepatic activity index

PT-INR

Prothrombin time international normalized ratio

TB

Total bilirubin

PP

Periportal

TM

Thrombomodulin

MELD

Model for end-stage liver disease

PDGF-AA

Platelet-derived growth factor A

PDGF-BB

Platelet-derived growth factor B

TGFB1

Transforming growth factor beta isoform 1

EGF

Epidermal growth factor

VEGF

Vascular endothelial growth factor

ICAM

Intercellular adhesion molecule

VCAM

Vascular cell adhesion molecule

TM

Thrombomodulin

GF

Growth factor

VIM

Vascular injury marker

CLD

Chronic liver disease

DEK

David E. Kleiner

IQR

Interquartile range

SD

Standard deviation

DAA

Direct acting antiviral therapy

Notes

Acknowledgments

We thank the patients, fellows, nurses, all staff, and institutional review board that assisted in the study.

Funding

This work was supported by the Intramural Research Program, National Institute of Diabetes and Digestive and Kidney Diseases.

Compliance with Ethical Standards

Conflicts of interest

All authors declare that they have no conflict of interest.

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Copyright information

© This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply 2019

Authors and Affiliations

  1. 1.Translational Hepatology Section, Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney DiseasesNational Institutes of HealthBethesdaUSA
  2. 2.Laboratory of PathologyNational Cancer Institute, National Institutes of HealthBethesdaUSA
  3. 3.National Institute of Diabetes and Digestive and Kidney DiseasesNational Institutes of HealthBethesdaUSA

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