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

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

Arshi Khanam  1 , Paul G Saleeb  2 , Shyam Kottilil  1
Affiliations
Review

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

Arshi Khanam et al. Cells. .

Abstract

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.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Mechanisms of liver fibrosis. Chronic liver injury mediated by different factors activates several parenchymal and non-parenchymal cells and induce cellular and molecular pathways that encourage hepatic inflammation by producing numerous inflammatory mediators. Extreme inflammation drives hepatic stellate cells activation, which then transform into proliferative and extracellular matrix producing myofibroblast leading to fibrosis and hepatic dysfunction. NAFLD: Non-alcoholic fatty liver disease, NASH: non-alcoholic steatohepatitis, DILI: drug-induced liver injury, KCs: kupffer cells, TGF-β: transforming growth factor beta, TNF-α: tumor necrosis factor alpha, TIM-4: T cell immunoglobulin and mucin-4, IRF-5: interferon regulatory factor-5, NLRP3: NLR family pyrin domain containing 3, HSC: hepatic stellate cell.
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