title: Cirrhosis--can we reverse hepatic fibrosis?
abstract: Cirrhosis, a pathological condition defined by deranged hepatic architecture resulting from progressive fibrosis, is the final common pathway through which nearly all chronic diseases of the liver produce morbidity and mortality. Historically, treatments for hepatic fibrosis have been directed against specific causes of chronic liver injury, and include corticosteroids for autoimmune hepatitis, interferon for hepatitis B and C, and iron depletion for haemochromatosis. However, there is no effective treatment for most causes of chronic liver disease. Fortunately, the past decade has witnessed great advances in our understanding of the fundamental pathophysiological mechanisms underlying fibrosis of the liver. It is now recognised that hepatic stellate cells (myofibroblast-like cells that encircle the sinusoids) are primarily responsible for hepatic fibrosis and subsequent progression to cirrhosis. In response to liver injury stellate cells undergo a phenotypic transformation that is termed activation, and characterised by chemotaxis, proliferation, contraction, fibrogenesis, and extracellular matrix degradation. Under conditions of persistent injury the behavioural responses of these stellate cells act in concert to bring about fibrosis of the liver. Recent investigations elucidating the signal transduction pathways that link hepatic injury to stellate cell function suggest novel targets at which treatment for fibrosis may be directed. For example, antagonism of TGF-beta receptor signaling has been shown to modulate fibrosis in animal models. This work, as well as other studies in both humans and animals, indicates that hepatic fibrosis may be slowed or reversed. These results suggest that a rational approach to treatment can be developed based on our detailed understanding of the molecular and cellular mechanisms underlying cirrhosis, which will have a major impact on the clinical management of patients with chronic liver disease.
authors.affiliation: Department of Medicine (Digestive Diseases), UCLA School of Medicine, Los Angeles, California 90095, USA.
authors.forename: Pisit
authors.initials: P
authors.lastname: Tangkijvanich
authors.forename: Hal F
authors.initials: HF
authors.lastname: Yee
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D018450:Disease Progression; D015536:Down-Regulation / Q000502:physiology; D042783:Endothelial Cells / Q000502:physiology; D005355:Fibrosis; D006509:Hepatitis B / Q000188:drug therapy; D017228:Hepatocyte Growth Factor / Q000502:physiology; D006801:Humans; D008099:Liver / Q000166:cytology / Q000473:pathology*; D008103:Liver Cirrhosis / Q000473:pathology* / Q000503:physiopathology; D010982:Platelet-Derived Growth Factor / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D016212:Transforming Growth Factor beta / Q000502:physiology
chemical_list: D010982:Platelet-Derived Growth Factor; D016212:Transforming Growth Factor beta; D017228:Hepatocyte Growth Factor