Antifibrotic therapies: will we ever get there?

Progressive hepatic fibrosis is the final common pathway for most chronic liver injuries, leading to cirrhosis with risk of liver failure and hepatocellular carcinoma. It is now recognized that fibrosis is a dynamic process, and may be reversible prior to the establishment of advanced architectural changes to the liver. The most effective antifibrotic strategy is to cure the underlying disease process before advanced fibrosis has developed. Unfortunately, this is often not possible, and specific antifibrotic therapies are needed. Advances in the understanding of the pathogenesis of liver fibrosis have identified several potential novel therapeutic targets, but unfortunately clinical development has been disappointing. One major limitation has been the often prolonged natural history of fibrosis compared to experimental models, and difficulties in accurate noninvasive fibrosis assessment, thus making clinical trial design difficult. In this review, we highlight the most promising current antifibrotic strategies.