Inhibition of hepatic fibrogenesis: a review of pharmacologic candidates.
Therapeutic attempts with anti-fibrotic drugs are still at an experimental stage. The clinical efficacies of most agents listed in Table II have not been proved. Some potential agents, such as colchicine, analogues of PGE, gamma-interferon, inhibitors of prolyl hydroxylase, malotilate, and PUL, must be further evaluated in controlled clinical trials. In addition, almost all anti-fibrotic agents, except HOE 077, are neither liver-nor fibrosis-specific. Some site-directed (targeted) drug delivery systems, drug-loaded vesicle carrier systems, like liposomes and erythrocyte ghosts, which selectively affect the extracellular matrix-producing cells, may improve efficacy and reduce adverse effects if they can be carriers for anti-fibrotic agents. Developments in biochemistry, immunohistochemistry, and molecular biology have considerably advanced our understanding of pathogenic mechanisms of hepatic fibrosis. With the development of available pathologic and serologic markers for ongoing fibrogenesis, experimental and clinical anti-fibrotic trials have become more active. Some therapeutic strategies have chosen targets for interference in collagen metabolism. In vivo inhibition of Ito cell activation has been a focus for the anti-fibrotic studies (70). In the present review an update of pharmacologic intervention in the process of metabolic pathways of collagen, the main extracellular matrices in both interstitium and basement membrane, has been summarized. Several drugs or biochemical agents that act on different steps of collagen synthesis, crosslinking, and breakdown are listed and discussed briefly. Moreover, agents that inhibit other matrix components are also involved in the review.(ABSTRACT TRUNCATED AT 250 WORDS)
Wu
J
J
Dept. of Histology and Cell Biology, University Hospital, University of Umeå, Sweden.
Danielsson
A
A
D003078:Colchicine / Q000627:therapeutic use; D006801:Humans; D007371:Interferon-gamma / Q000627:therapeutic use; D008103:Liver Cirrhosis / Q000517:prevention & control*; D008314:Malonates / Q000627:therapeutic use; D011393:Procollagen-Proline Dioxygenase / Q000037:antagonists & inhibitors; D011459:Prostaglandins E, Synthetic / Q000627:therapeutic use
D008314:Malonates; D011459:Prostaglandins E, Synthetic; D007371:Interferon-gamma; D011393:Procollagen-Proline Dioxygenase; C024808:diisopropyl 1,3-dithiol-2-ylidenemalonate; D003078:Colchicine