+ Site Statistics
+ Search Articles
+ Subscribe to Site Feeds
EurekaMag Most Shared ContentMost Shared
EurekaMag PDF Full Text ContentPDF Full Text
+ PDF Full Text
Request PDF Full TextRequest PDF Full Text
+ Follow Us
Follow on FacebookFollow on Facebook
Follow on TwitterFollow on Twitter
Follow on Google+Follow on Google+
Follow on LinkedInFollow on LinkedIn

+ Translate

Translating an understanding of the pathogenesis of hepatic fibrosis to novel therapies

Clinical Gastroenterology and Hepatology 11(3): 224-31.E1-5

Translating an understanding of the pathogenesis of hepatic fibrosis to novel therapies

The response to injury is one of wound healing and fibrogenesis, which ultimately leads to fibrosis. The fibrogenic response to injury is a generalized one across virtually all organ systems. In the liver, the injury response, typically occuring over a prolonged period of time, leads to cirrhosis (although it should be pointed out that not all patients with liver injury develop cirrhosis). The fact that many different diseases result in cirrhosis suggests a common pathogenesis. The study of hepatic fibrogenesis over the past 2 decades has been remarkably active, leading to a considerable understanding of this process. It has been clearly demonstrated that the hepatic stellate cell is a central component in the fibrogenic process. It has also been recognized that other effector cells are important in the fibrogenic process, including resident fibroblasts, bone marrow derived cells, fibrocytes, and even perhaps cells derived from epithelial cells (i.e., through epithelial to mesenchymal transition or EMT). A key aspect of the biology of fibrogenesis is that the fibrogenic process is dynamic; thus, even advanced fibrosis (or cirrhosis) is reversible. Together, an understanding of the cellular basis for liver fibrogenesis, along with multiple aspects of the basic pathogenesis of fibrosis, have highlighted many exciting potential therapeutic opportunities. Thus, while the most effective anti-fibrotic therapy is treatment of the underlying disease, in situations in which this not possible, specific anti-fibrotic therapy is likely to not only become feasible, but will soon become a reality. The goal of this review is to highlight the mechanisms underlying fibrogenesis that may be translated into future anti-fibrotic therapies and to review the current state of clinical development.

Accession: 036708067

PMID: 23305825

DOI: 10.1016/j.cgh.2013.01.005

Related references

Friedman, S.L., 2008: Preface. Hepatic fibrosis: pathogenesis, diagnosis, and emerging therapies. Clinics in Liver Disease 12(4): Xiii-Xxiv

King, T.E., 2006: Idiopathic interstitial pneumonias: translating our current understanding into novel therapies. Experimental Lung Research 31 Suppl 1: 41-46

Thannickal, V.J.; Roman, J., 2010: Challenges in translating preclinical studies to effective drug therapies in idiopathic pulmonary fibrosis. American Journal of Respiratory and Critical Care Medicine 181(6): 532-533

Weiskirchen, R.; Tacke, F., 2016: Liver Fibrosis: From Pathogenesis to Novel Therapies. Chronic liver injury is accompanied by a dysbalanced scarring process, termed fibrosis. This process is mainly driven by chronic inflammation and an altered activity of a multitude of different chemokines and cytokines, resulting in the infiltrati...

Pleyer, U.; Hazirolan, D.; Stübiger, N., 2012: Comments on the pathogenesis of Behçet's disease. A key to understanding new therapies?. The etiology and pathogenesis of Behçet's syndrome remains unclear. It has been postulated that an infectious agent may induce an immune-mediated, generalized vasculitis in genetically predisposed individuals (HLA-B51 +). There is accumula...

Kucharzik, T.; Maaser, C.; Lügering, A.; Kagnoff, M.; Mayer, L.; Targan, S.; Domschke, W., 2006: Recent understanding of IBD pathogenesis: implications for future therapies. The inflammatory bowel diseases (IBD) are comprised of two major phenotypes, Crohn's disease (CD) and ulcerative colitis (UC). Research over the last couple of years has led to great advances in understanding the inflammatory bowel diseases a...

Koyama, Y.; Brenner, D.A., 2016: New therapies for hepatic fibrosis. Liver fibrosis is an outcome of many chronic diseases, and often results in cirrhosis, liver failure, and portal hypertension. Liver transplantation is the only treatment available for patients with advanced stages of liver cirrhosis. Therefore, a...

Dhooghe, B.; Noël, S.; Huaux, Fçois.; Leal, T., 2014: Lung inflammation in cystic fibrosis: pathogenesis and novel therapies. Despite remarkable progress following the identification of the causing gene, the final outcome of cystic fibrosis (CF) remains determined mainly by the progressive reduction of lung function. Inflammation of the airways is one of the key elements...

Friedman, S.L., 2016: Hepatic Fibrosis: Emerging Therapies. There has been tremendous progress made in understanding the pathogenesis of hepatic fibrosis, which has created new opportunities for the treatment of this condition. Clinical evidence of fibrosis reversibility has established that the liver has...

Bononi, A.; Napolitano, A.; Pass, H.I.; Yang, H.; Carbone, M., 2016: Latest developments in our understanding of the pathogenesis of mesothelioma and the design of targeted therapies. Malignant mesothelioma is an aggressive cancer whose pathogenesis is causally linked to occupational exposure to asbestos. Familial clusters of mesotheliomas have been observed in settings of genetic predisposition. Mesothelioma incidence is antic...