Fibrosis in the liver: acute protection and chronic disease

The understanding of the cellular and molecular mechanisms of the fibrotic wound-healing response of the liver has made dramatic progress in the past 20 years. Hepatic stellate cells (HSCs), which after liver injury proliferate and transdifferentiate to myofibroblasts, have emerged as the primary source of the fibrotic response, even though other fibrogenic cells may also contribute to the production of extracellular matrix (ECM). Advances in the understanding of HSC regulation include apoptotic signaling, angiogenic signaling, and responses to oxidative stress. The ECM has emerged not only as a structural scaffold, but also as a dynamic and interactive matrix regulating stellate cell activation. Additionally, the innate immune system and immune signaling, as well as a broadening understanding of the transcriptional regulation including microRNAs and epigenetic events offer potential therapeutic targets. Unraveling genetic determinants related to mechanisms of hepatic fibrogenesis promise individualized therapy or prevention. Hepatic fibrosis and cirrhosis have emerged as treatable and potentially reversible consequence of chronic liver disease.