Liver Fibrosis: Therapeutic Targets and Advances in Drug Therapy

Abstract

Liver fibrosis is an abnormal wound repair response caused by a variety of chronic liver injuries, which is characterized by over-deposition of diffuse extracellular matrix (ECM) and anomalous hyperplasia of connective tissue, and it may further develop into liver cirrhosis, liver failure or liver cancer. To date, chronic liver diseases accompanied with liver fibrosis have caused significant morbidity and mortality in the world with increasing tendency. Although early liver fibrosis has been reported to be reversible, the detailed mechanism of reversing liver fibrosis is still unclear and there is lack of an effective treatment for liver fibrosis. Thus, it is still a top priority for the research and development of anti-fibrosis drugs. In recent years, many strategies have emerged as crucial means to inhibit the occurrence and development of liver fibrosis including anti-inflammation and liver protection, inhibition of hepatic stellate cells (HSCs) activation and proliferation, reduction of ECM overproduction and acceleration of ECM degradation. Moreover, gene therapy has been proved to be a promising anti-fibrosis method. Here, we provide an overview of the relevant targets and drugs under development. We aim to classify and summarize their potential roles in treatment of liver fibrosis, and discuss the challenges and development of anti-fibrosis drugs.

Macrophage Polarization and Its Role in Liver Disease

“…This is perhaps a potential mechanism by which M2 macrophages ameliorate ALD and MAFLD. LF is a chronic liver disease resulting from the excessive repair of liver tissue injury, characterized by excessive deposition of ECM in the liver, which manifests as intrahepatic connective tissue dysplasia (278). Due to extensive etiologies, such as common CCl 4 and schistosome infection in research, the pathogenesis of LF is not consistent (279).…”

Structural and Temporal Dynamics of Mesenchymal Stem Cells in Liver Diseases From 2001 to 2021: A Bibliometric Analysis

“…In basic studies, the mechanism of MSCs in treating liver cirrhosis has been evaluated from multiple perspectives. Chronic injury factors such as hepatitis virus and alcohol can gradually destroy the endothelial barrier and liver cells, causing inflammatory cell infiltration and activating hepatic stellate cells (HSCs) ( 87 ). Activation of HSCs (aHSCs) obtains a phenotype of myofibroblasts characterized by increased expression of α-smooth muscle actin (α-SMA) and increased production of ECM components, growth factors and cytokines, which is the main determinant during liver fibrosis ( 88 ).…”

Role of IQ Motif-Containing GTPase-Activating Proteins in Hepatocellular Carcinoma

“…Fibrosis is an aberrant tissue restoration process in response to long-term and persistent liver injuries that may further develop into liver cirrhosis, failure, or cancer if left untreated. Hitherto, chronic liver diseases coupled with fibrotic liver have resulted in remarkable worldwide morbidity and mortality ( 82 – 84 ). Since IQGAP1 is one of the vital scaffolding proteins that have established pivotal roles in cytoskeleton remodeling and rearrangements of cellular networks and various vital cellular processes.…”