Hepatic Fibrosis

Hepatic fibrosis is a reversible wound-healing response characterized by the accumulation of extracellular matrix (ECM) or "scar;" it follows chronic, but not self-limited, liver disease. The ECM components in fibrotic liver are similar, regardless of the underlying cause. Activation or transdifferentiation of hepatic stellate cells into contractile myofibroblasts is the central event in hepatic fibrosis. Resident activated stellate cells and other myofibroblasts derived from intra- and extrahepatic sources orchestrate the accumulation of cytokines, production and degradation of the normal ECM, vascular and organ contraction, and modulation of inflammation. Both hepatic fibrosis and even cirrhosis may be reversible, however the exact stage at which cirrhosis becomes irreversible is not known. Cirrhosis represents a continuum of progressive ECM accumulation and risk of decompensation, yet patients may be asymptomatic for many years. The methods for noninvasive staging of hepatic fibrosis have improved significantly and can replace liver biopsy in many patients. Emerging antifibrotic therapies target key cytokines, receptors, and soluble molecules associated with stellate cell activation and inflammation. Clinical trials of antifibrotic therapies are well underway, and continued progress is anticipated that will ultimately yield new approaches for patients with fibrotic liver disease.