Emerging therapies for liver fibrosis.
Liver fibrosis occurs as a result of a wide range of injurious processes and in its end-stage results in cirrhosis. This gross disruption of liver architecture is associated with impaired hepatic function, portal hypertension and significant resultant morbidity and mortality. Indeed, liver fibrosis and cirrhosis represent a major worldwide healthcare burden. Recent progress in liver transplantation, the management of portal hypertension and the treatment of chronic viral hepatitis have had an important impact. However, these approaches are not without their limitations - in particular, issues regarding organ availability for transplantation - and serve to highlight the urgent requirement to influence pharmacologically the underlying fibrotic process in many patients. Liver fibrosis has been shown to be a bidirectional process and increasing data from laboratory and clinical studies reveal that even advanced fibrosis and cirrhosis are potentially reversible. Exploration of the molecular mechanisms underlying this bi-directionality will lead to char acterisation of the essential attributes of an antifibrotic therapy. In this review, these mechanisms are highlighted and the growing number of emerging antifibrotic agents discussed.
Fowell
Andrew J
AJ
Liver Research Group, Division of Infection, Inflammation and Repair, University of Southampton, Southampton General Hospital, Southampton, UK. C.A.Gilchrist@ed.ac.uk
Iredale
John P
JP
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D000975:Antioxidants / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D006801:Humans; D008103:Liver Cirrhosis / Q000188:drug therapy* / Q000473:pathology; D020011:Protective Agents / Q000627:therapeutic use*; D016896:Treatment Outcome
D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D020011:Protective Agents