Pathophysiology and pharmacologic modulation of hepatic fibrosis

Most chronic liver disorders are accompanied morphologically by the deposition of fibrous tissue within the hepatic parenchyma. This fibrotic tissue compromises hepatic function and contributes significantly to hepatic failure. Fibrosis is a dynamic process associated with the continual deposition and resorption of connective tissue. Therapeutic strategies are emerging whereby this dynamic process can be modulated. Since collagen is the major component of the extracellular matrix deposited in hepatic fibrosis, most anti-fibrotic therapies have been directed toward the control of collagen metabolism. After collagen genes are transcribed and translated into precursor procollagen proteins, a number of post-translational modifications that ensure the deposition of structurally sound collagen within the extracellular matrix occur. A number of drugs can specifically modulate collagen biosynthesis at the transcriptional level or at various post-translational stages. These anti-fibrotic drugs include corticosteroids, azathioprine, penicillamine, colchicine, zinc, prostaglandins, cyclosporine, and interferons. The pharmacologic action of these drugs and the clinical role in veterinary and human fibrotic hepatopathies will be discussed.