Liver Fibrosis: Mechanistic Concepts and Therapeutic Perspectives

Abstract

Liver fibrosis due to viral or metabolic chronic liver diseases is a major challenge of global health. Correlating with liver disease progression, fibrosis is a key factor for liver disease outcome and risk of hepatocellular carcinoma (HCC). Despite different mechanism of primary liver injury and disease-specific cell responses, the progression of fibrotic liver disease follows shared patterns across the main liver disease etiologies. Scientific discoveries within the last decade have transformed the understanding of the mechanisms of liver fibrosis. Removal or elimination of the causative agent such as control or cure of viral infection has shown that liver fibrosis is reversible. However, reversal often occurs too slowly or too infrequent to avoid life-threatening complications particularly in advanced fibrosis. Thus, there is a huge unmet medical need for anti-fibrotic therapies to prevent liver disease progression and HCC development. However, while many anti-fibrotic candidate agents have shown robust effects in experimental animal models, their anti-fibrotic effects in clinical trials have been limited or absent. Thus, no approved therapy exists for liver fibrosis. In this review we summarize cellular drivers and molecular mechanisms of fibrogenesis in chronic liver diseases and discuss their impact for the development of urgently needed anti-fibrotic therapies.

Dendritic Cell and T Cell Crosstalk in Liver Fibrogenesis and Hepatocarcinogenesis: Implications for Prevention and Therapy of Liver Cancer

“…However, there is an emerging body of evidence describing important contributions of adaptive immune cells to chronic liver diseases and fibrosis [ 62 , 63 ]. Several studies point towards a profibrotic role of the T cell response whilst the progression of cirrhosis in turn disrupts T cell function [ 49 , 64 ].…”

Molecular Pathways Modulated by Mesenchymal Stromal Cells and Their Extracellular Vesicles in Experimental Models of Liver Fibrosis

“…Chronic liver disease (CLD) may be caused by different types of injury (viral infection, alcohol abuse, NASH, ischemic injury, chemical compounds, autoimmune and genetic diseases, etc. ), and it is one of the major global health problems that causes about 2 million deaths per year worldwide (Asrani et al, 2019;Roehlen et al, 2020). Fibrosis is the main characteristic of CLD and is due to an excessive ECM accumulation, which compromises the normal morphology and function of the liver.…”

Anti-Cancer Effects of Green Tea Epigallocatchin-3-Gallate and Coffee Chlorogenic Acid

“…Similar results were reported by Wang et al [ 137 ] who showed that CGA could inhibit schistosomiasis-induced liver fibrosis through IL-13/miR-21/Smad7 signaling interactions in LX2 cells and schistosome-infected mice. Since liver fibrosis is a key factor for the risk of HCC [ 138 ], CGA might be useful for its prevention.…”