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Extracellular Matrix Remodeling with Focus on Biochemical Markers in Liver Fibrosis: Limitations and Possibilities

  • Mette Juul NielsenEmail author
  • Morten A. Karsdal
  • Aleksander Krag
  • Diana Julie Leeming
Chapter

Abstract

Liver fibrosis is the common factor of liver diseases regardless of the underlying cause. Continuous accumulation of extracellular matrix (ECM) proteins will eventually lead to organ failure. The extracellular matrix is composed of fibrous and non-fibrous collagens, elastin, and proteoglycans. In advanced stages of fibrosis the balance of the ECM remodeling is disturbed resulting in alterations of the quality and constitution of ECM liver proteins. As a result, the extracellular matrix density maximizes and a superfluous build-up of fibrous tissue as well as a general change in the protein profile and liver structure occurs. In fact, compared with a healthy liver, a cirrhotic liver may comprise nearly six times as much collagen; where type I and III collagens are the most plentiful. Formation and disease relevant degradation products of extracellular and intracellular proteins released into the circulation are the result of the extracellular matrix remodeling. Serving as serological biomarker targets these fragments can hold valuable clues about the disease pathogenesis. Being able to identify early signs of liver fibrosis with the aim of stopping further progression is a clinical need. Unlike in histology, serological markers can potentially mirror both the activity of the fibrotic processes and the total extracellular matrix mass going through a modification. The most prevalent ECM remodeling markers such as hyaluronic acid, N-terminal procollagen type III, and type IV collagen will be discussed in the following chapter. A novel alternative: The Protein Fingerprint Technology will also be introduced. This technology has become widely recognized for its ability to identify and quantify disease-specific protein fragments in body liquids, demonstrating a sound potential as a serological biomarker of extracellular matrix remodeling in fatty liver diseases with fibrosis.

Keywords

Extracellular matrix Remodeling Fibrosis Collagen Biomarkers Neo-epitope 

Abbreviations

ALD

Alcoholic liver disease

ALT

Alanine aminotransferase

AST

aspartate aminotransferase

AUC

Area under receiver operator characteristics curve

BIPED

Burden of disease, Investigative, Prognostic, Efficacy of intervention, Diagnostic

C3M

Type III collagen degradation fragment

ECM

Extracellular matrix

ELF

Enhanced liver fibrosis

FACIT

fibril-associated collagens

FDA

Food and drug administration

HA

Hyaluronic acid

HALT-C

Hepatitis C Antiviral Long-term Treatment against Cirrhosis

HBV

Hepatitis B virus

HCV

Hepatitis C virus

HSC

Hepatic stellate cells

MMP

Matrix metalloproteinase

NAFLD

Non-alcoholic liver disease

NPV

Negative predictive value

PIIINP

N-terminal type III collagen propeptide

PPV

Positive predictive value

Pro-C3

True type III collagen formation fragment

PTM

Post-translational modification

TIMP

Tissue inhibitor of metalloproteinase

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Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Mette Juul Nielsen
    • 1
    Email author
  • Morten A. Karsdal
    • 1
  • Aleksander Krag
    • 2
  • Diana Julie Leeming
    • 1
  1. 1.Nordic Bioscience, Biomarkers and ResearchHerlevDenmark
  2. 2.Department of Gastroenterology and HepatologyUniversity of Southern Denmark, Odense University HospitalOdenseDenmark

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