HISTOLOGY AND HISTOPATHOLOGY

Cellular and Molecular Biology

 

Review

Liver fibrosis: a dynamic and potentially reversible process

Davide Povero1,2*, Chiara Busletta1,2*, Erica Novo1,2, Lorenzo Valfrè di Bonzo1,2, Stefania Cannito1,2, Claudia Paternostro1,2 and Maurizio Parola1,2

1Department of Experimental Medicine and Oncology and 2Interuniversitary Centre of Hepatic Pathophysiology, University of Torino, Italy
* These two authors contributed equally to the present study.

Offprint requests to: Maurizio Parola, Dip. Medicina e Oncologia Sperimentale, Università degli Studi di Torino, Corso Raffaello 30, 10125 Torino, Italy. e-mail: maurizio.parola@unito.it


Summary. In any chronic liver disease (CLDs), whatever the aetiology, reiteration of liver injury results in persisting inflammation and progressive fibrogenesis, with chronic activation of the wound healing response in CLDs, representing a major driving force for progressive accumulation of ECM components, eventually leading to liver cirrhosis. Cirrhosis is characterized by fibrous septa dividing the hepatic parenchyma into regenerative pseudo-lobules, as well as by extensive changes in vascular architecture, the development of portal hypertension and related complications. Liver fibrogenesis (i.e., the dynamic process leading to increased deposition of ECM and much more) can lead to different patterns of fibrosis and is sustained by myofibroblast-like cells (MFs) of different origin, with activated hepatic stellate cells (HSC/MFs) being the major cell type involved. Major pro-fibrogenic mechanisms also include oxidative stress, as well as derangement of epithelial-mesenchymal interactions and, as recently suggested, the process of epithelial to mesenchymal transition (EMT).
Liver fibrosis has been considered traditionally as an irreversible process but experimental and clinical literature data published in the last decade have suggested that both the removal of the aetiological agent or condition, as well as an effective therapy, can result in significant regression of liver fibrosis. This is usually associated, particularly in animal models, with induction of apoptosis in MFs but, unfortunately, human HSC/MFs are much more resistant to apoptosis than murine MFs. However, clinical studies provided no unequivocal evidence for a complete reversal of cirrhosis or a significant reversal of vascular changes in conditions of established cirrhosis
. Histol Histopathol 25, 1075-1091 (2010)

Key words: Liver fibrosis, Hepatic stellate cells, Hepatic myofibroblasts, Liver cirrhosis, Myofibroblast apoptosis

DOI: 10.14670/HH-25.1075