title: Resolution of liver fibrosis: basic mechanisms and clinical relevance.
abstract: With evidence from a large number of animal models and clinical trials, it is now beyond debate that liver fibrosis and even cirrhosis are potentially reversible if the underlying cause can be successfully eliminated. However, in a significant proportion of patients cure of the underlying disease may not result in fibrosis regression or a significant reduction of the risk for hepatocellular carcinoma development. Understanding of the mechanistic pathways and regulatory factors that characterize matrix remodeling and architectural repair during fibrosis regression may provide therapeutic approaches to induce or accelerate regression as well as novel diagnostic tools. Recent seminal observations have determined that in resolving liver fibrosis a significant proportion of hepatic stellate cell-myofibroblasts (HSC-MFs) can revert to a near quiescent phenotype. Hepatic macrophages derived from inflammatory monocytes may contribute to fibrosis resolution through an in situ phenotypic switch mediated by phagocytosis. Emerging therapeutic approaches include deletion or inactivation of HSC-MFs, modulation of macrophage activity and autologous cell infusion therapies. Novel noninvasive diagnostic tests such as serum and imaging markers responsive to extracellular matrix degradation are being developed to evaluate the clinical efficacy of antifibrotic interventions.
authors.affiliation: The University of Edinburgh/ Medical Research Council (MRC) Centre for Inflammation Research, Queen's Medical Research Institute, Edinburgh, United Kingdom.
authors.forename: Prakash
authors.initials: P
authors.lastname: Ramachandran
authors.affiliation: The University of Edinburgh/ Medical Research Council (MRC) Centre for Inflammation Research, Queen's Medical Research Institute, Edinburgh, United Kingdom.
authors.forename: John P
authors.initials: JP
authors.lastname: Iredale
authors.affiliation: The University of Edinburgh/ Medical Research Council (MRC) Centre for Inflammation Research, Queen's Medical Research Institute, Edinburgh, United Kingdom.
authors.forename: Jonathan A
authors.initials: JA
authors.lastname: Fallowfield
mesh_terms: D000818:Animals; D055166:Hepatic Stellate Cells / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D008103:Liver Cirrhosis / Q000378:metabolism / Q000473:pathology*; D020127:Recovery of Function; D015398:Signal Transduction