A Review of Liver Fibrosis and Emerging Therapies

• Main Authors: Rooshi Nathwani, Benjamin H. Mullish, David Kockerling, Roberta Forlano, Pinelopi Manousou, Ameet Dhar
• Format: Article
• Language: English
• Published: European Medical Journal 2019-12-01
• Series: European Medical Journal
• Subjects: anticoagulation; antifibrotic therapy; fibrosis; hepatic fibrosis; hepatic stellate cell
• Online Access: https://www.emjreviews.com/hepatology/article/a-review-of-liver-fibrosis-and-emerging-therapies/

With the increasing burden of liver cirrhosis, the most advanced stage of hepatic fibrosis, there is a need 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 nonalcoholic steatohepatitis. Fibrosis, characterised by the accumulation of extracellular matrix proteins, is caused by 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, which is the principal cell type involved. Experimental models using rodent and human cell lines of liver injury have assisted in better understanding of 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. Current types of experimental models used to induce fibrosis, as well as up-to-date anticoagulant therapies and agents targeting the hepatic stellate cell that have been trialled in animal and human studies with antifibrotic properties, are also reviewed.