A review of liver fibrosis and emerging therapies
File(s)
Published version
Author(s)
Type
Journal Article
Abstract
With an increasing burden of liver cirrhosis, the most advanced stage of hepatic fibrosis, there is an emphasis to better understand the pathological processes and mechanisms to target specific treatments to reverse or cease fibrosis progression. Antiviral therapy for hepatitis B and C has effectively treated underlying causes of chronic liver disease and has induced fibrosis reversal in some however, this has not been targeted for the majority of aetiologies for cirrhosis including alcohol or non-alcoholic steatohepatitis. Fibrosis, characterized by the accumulation of extracellular matrix proteins, occurs due to chronic injury from toxic, infectious or metabolic causes. The primary event of fibrogenesis is increased matrix production and scar formation mediated by the hepatic stellate cell, the principal cell type involved. Experimental models using rodent and human cell lines of liver injury have assisted in better understanding fibrogenesis especially in recognising the role of procoagulant factors. This has led to interventional studies using anticoagulants in animal models with reversal of fibrosis as the primary endpoint. Though these trials have been encouraging, no antifibrotic therapies are currently licenced for human use. This literature review discusses current knowledge in the pathophysiology of hepatic fibrosis, including characteristics of the extracellular matrix, signalling pathways and hepatic stellate cells. We also review current types of experimental models used to induce fibrosis and up-to46 date anticoagulant therapies and agents targeting the hepatic stellate cell that have been trialled in animal and human studies with anti-fibrotic properties.
Date Issued
2019-12
Date Acceptance
2019-08-01
Citation
European Medical Journal Gastroenterology, 2019, 4 (4), pp.105-116
ISSN
2054-6203
Publisher
European Medical Journal
Start Page
105
End Page
116
Journal / Book Title
European Medical Journal Gastroenterology
Volume
4
Issue
4
Copyright Statement
© 2019 European Medical Group LTD trading as European Medical Journal. Creative Commons Attribution-Non Commercial 4.0
Sponsor
Medical Research Council
Medical Research Council (MRC)
Identifier
https://www.emjreviews.com/hepatology/article/a-review-of-liver-fibrosis-and-emerging-therapies/
Grant Number
MR/R00875/1
MR/R000875/1
Subjects
1103 Clinical Sciences
1101 Medical Biochemistry and Metabolomics
Gastroenterology & Hepatology
Publication Status
Published
Date Publish Online
2019-12-12