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

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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).

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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

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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.

Author information

Author notes

  1. Rabab O. Ali and Mi Sun Moon contributed equally to this work.

Authors and Affiliations

  1. 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

    Rabab O. Ali, Mi Sun Moon, Elizabeth C. Townsend, Kareen Hill, Grace Y. Zhang, Alyson Bradshaw, Hannah Guan, Destanee Hamilton, Christopher Koh & Theo Heller

  2. Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA

    David E. Kleiner

  3. National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA

    Sungyoung Auh

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  1. Rabab O. Ali
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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

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