Pathophysiology and Treatment Options for Hepatic Fibrosis: Can It Be Completely Cured?

Cells. 2021 May 4;10(5):1097. doi: 10.3390/cells10051097.


Hepatic fibrosis is a dynamic process that occurs as a wound healing response against liver injury. During fibrosis, crosstalk between parenchymal and non-parenchymal cells, activation of different immune cells and signaling pathways, as well as a release of several inflammatory mediators take place, resulting in inflammation. Excessive inflammation drives hepatic stellate cell (HSC) activation, which then encounters various morphological and functional changes before transforming into proliferative and extracellular matrix (ECM)-producing myofibroblasts. Finally, enormous ECM accumulation interferes with hepatic function and leads to liver failure. To overcome this condition, several therapeutic approaches have been developed to inhibit inflammatory responses, HSC proliferation and activation. Preclinical studies also suggest several targets for the development of anti-fibrotic therapies; however, very few advanced to clinical trials. The pathophysiology of hepatic fibrosis is extremely complex and requires comprehensive understanding to identify effective therapeutic targets; therefore, in this review, we focus on the various cellular and molecular mechanisms associated with the pathophysiology of hepatic fibrosis and discuss potential strategies to control or reverse the fibrosis.

Keywords: Kupffer cells; exosomes; extracellular matrix; hepatic stellate cells; hepatocytes; inflammasomes; inflammation; liver fibrosis; miRNA.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / therapeutic use
  • Exosomes / metabolism
  • Humans
  • Inflammasomes / metabolism
  • Liver Cirrhosis / drug therapy
  • Liver Cirrhosis / etiology
  • Liver Cirrhosis / metabolism*
  • MicroRNAs / genetics
  • MicroRNAs / metabolism
  • Molecular Targeted Therapy / methods*


  • Anti-Inflammatory Agents
  • Inflammasomes
  • MicroRNAs