title: Future mechanistic strategies for tackling fibrosis--an unmet need in liver disease.
abstract: Standardised mortality rates for liver disease in the UK have increased 400% since 1970. However, evidence from a large number of animal models and clinical trials indicates that liver fibrosis and even cirrhosis are potentially reversible if the underlying cause can be successfully removed. Nevertheless, in a significant number of patients cure of the underlying disease may not result in fibrosis regression, and no antifibrotic drug has been licenced by the United States Food and Drug Administration or the European Medicines Agency. Dissection of the mechanistic pathways and regulatory factors that characterise matrix remodelling and architectural repair during fibrosis regression are revealing novel therapeutic approaches to induce liver repair. Points of attack in the fibrotic cascade include promoting the loss of hepatic myofibroblasts, inhibiting profibrogenic properties of myofibroblasts, stimulating degradation of accumulated liver scar tissue, targeting the immune response, and cell-based therapies. Therapeutic candidates are now being evaluated in early-phase human trials but translation into the clinic will require careful patient selection and stratification, and the definition and validation of clinically meaningful endpoints.
authors.affiliation: MRC/University of Edinburgh Centre for Inflammation Research, Queen's Medical Research Institute, Edinburgh, UK.
authors.forename: Jonathan A
authors.initials: JA
authors.lastname: Fallowfield
mesh_terms: D006801:Humans; D008103:Liver Cirrhosis / Q000188:drug therapy / Q000276:immunology / Q000503:physiopathology
keywords: Liver fibrosis; antifibrotic therapy; reversibility