Abstract: The present invention is based on the finding that the artificial induction of hepatic stellate cell (HSC) apoptosis in vivo can promote the resolution of liver fibrosis. Thus, the present invention provides methods for treating liver disease in a subject involving administration of an inducer of apoptosis which is capable of selectively inducing hepatic stellate cell apoptosis in the liver of the subject or of an agent which is capable of giving rise to such an inducer in the subject. In addition, the invention provides methods for treating liver fibrosis in a subject comprising the selective delivery of an inducer of apoptosis specifically to the hepatic stellate cells of the subject or of an agent which is capable of giving rise to an inducer of hepatic stellate cell apoptosis.

Abstract: Provided are methods of inhibiting proliferation and/or trans-differentiation of hepatic stellate cells, which method comprises the step of contacting hepatic stellate cells with a ligand of the low affinity glucocorticoid binding site (LAGS), which may be the rat p28 receptor or the human hpr6.6 receptor. The invention also provides ligands for use in such methods (e.g. pregnenolone 16-alpha carbonitrile) and methods for screening for the same (e.g. based on competition or displacement assays using LAGS ligands such as dexamethasone). Such ligands may be used in the treatment of liver disorders.