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.

Highlights

  • Liver fibrosis is an abnormal repair reaction for chronic liver injury caused by various causes, such as chronic hepatitis B (CHB), chronic hepatitis C (CHC) and alcoholic fatty liver disease (AFLD)

  • Many causes will lead to the imbalance of pro-fibrosis/antifibrosis mechanism and promote the occurrence and development of liver fibrosis, such as the excessive production and secretion of pro-inflammatory cytokines, the increase of hepatocyte apoptosis, the proliferation of activated hepatic stellate cells (HSCs), and the excessive production and deposition of extracellular matrix (ECM)

  • The anti-hepatic fibrosis candidate drugs that are at the forefront of research with a good development momentum mainly include OCA, resmetirom, CVC, selonsertib, and elafibranor

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Summary

Introduction

Liver fibrosis is an abnormal repair reaction for chronic liver injury caused by various causes, such as chronic hepatitis B (CHB), chronic hepatitis C (CHC) and alcoholic fatty liver disease (AFLD) It is characterized by diffuse excessive production and deposition of extracellular matrix (ECM) in liver (Poynard et al, 1997; Benhamou et al, 1999; Pinzani and Macias-Barragan, 2010; Povero et al, 2010). With the pro-inflammatory reaction, the normal structure and physiological function of the liver tissues are gradually destroyed, which causes the production of scar tissues replacing the liver parenchyma. It further develops into liver cirrhosis, liver failure or liver cancer, which eventually leads to the death of the patients (Zoubek et al, 2017).

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