The preliminary results of a prospective double-blind controlled trial of colchicine in 100 patients with hepatitis B virus-related cirrhosis are reported. The patients, 94 males and 6 females, aged 32-80, were assigned to receive either 1 mg of colchicine or an identical placebo orally on a daily basis. The duration of the follow up ranged from 15 to 51 months (median 26 months). Seventy percent had histological proof of cirrhosis. On entry, 80 patients were in Child-Pugh class A, 19 were in class B, and one was in class C. Compared to the placebo group, there was no improvement in the colchicine group after a 24-month follow up in any of the biochemistry data, for example, serum albumin, alkaline phosphatase, alanine and aspartate aminotransferase, bilirubin, and prothrombin time. The difference in the cumulative survival rates at 51 months did not reach statistical significance (p = 0.8) in either group. There was no histological improvement in 30 patients who were willing to undergo repeated liver biopsies. No trend toward improvement of the hepatic pressure gradient was observed in these patients. The serum levels of aminopropeptide of type III procollagen increased significantly in patients in both groups after 24 months of therapy (1.07 +/- 0.06 vs. 1.36 +/- 0.06 U/ml in the colchicine group, 0.93 +/- 0.09 vs. 1.25 +/- 0.07 U/ml in the placebo group; p < 0.05). In addition, neither the clinical deterioration of cirrhosis nor death was prevented in patients receiving colchicine therapy. This report indicates that colchicine has no effect in the treatment of HBV-related postnecrotic cirrhosis.
"Colchicine is an anti-inflammatory agent that under some conditions suppresses collagen formation and/or stimulates collagenase. An early report on its use in patients with advanced fibrosis or cirrhosis was encouraging (Kershenobich et al., 1988) but has not been replicated, and randomized trials of patients with primary biliary cirrhosis (Kaplan et al., 1986; Kaplan et al., 1999) or chronic viral hepatitis (Wang et al., 1994) have been negative. Corticosteroids are useful for diseases that benefit from broad immunosuppression, such as autoimmune hepatitis. "
[Show abstract][Hide abstract] ABSTRACT: Cells termed myofibroblasts are prominent in the injury response of all epithelial tissues. They exhibit proliferation, migration, production of collagen and other extracellular matrix (ECM) molecules, and con- traction, all for containing the injury and closing the wound. When the injury is limited in time, the final stage of the repair involves a dismantling of the cel- lular apparatus and restoration of normal tissue structure. With multiple cycles of repair, however, there is net accumulation of ECM, to the detriment of tissue structure and function. Repair-related ECM coalesces into fibrous bundles and, over time, undergoes changes that render it resistant to degra- dation. The result is a scar. In the skin, a scar may have cosmetic importance only. In the liver, how- ever, extensive scarring is the setting for unregu- lated growth and neoplasia; also, fibrous bands dis- rupt normal blood flow, leading to portal hyperten- sion and its complications. With regard to therapy for fibrosis, the first consideration is elimination of the injury factor. However, given that many liver dis- eases do not have effective therapies at present, strategies targeting fibrogenesis per se are under development. The main source of myofibroblast-like cells and ECM production in the liver is the perisinu- soidal stellate cell, which responds to injury with a pleiotypic change termed activation. Activation is orchestrated by cytokines and the ECM itself. Among the cytokines involved in this process, transforming growth factor-beta (TGF-β) is particularly prominent. The early changes in ECM include de novo produc- tion of a specific "fetal" isoform of fibronectin, which arises from sinusoidal endothelial cells. It is stimu- lated by TGF-β and acts directly on stellate cells to promote their activation. Based on these and other advances in understanding the fundamentals of the injury response, several strategies now exist for altering fibrogenesis, ranging from agents that block TGF-β to traditional Chinese herbal extracts. Arrest of fibrogenesis, even with underlying cirrhosis, is likely to extend life or prolong the time to transplant. Whether it reduces the risk of hepatocellular carci- noma remains to be proven. Although TGF-β antag- onists are effective anti-fibrogenic agents, they will require detailed safety testing because of the finding that several forms of epithelial neoplasia are associ- ated with altered regulation of TGF-β.
Experimental and Molecular Medicine 12/2001; 33(4). DOI:10.1038/emm.2001.31 · 3.45 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: There is no medical treatment of documented benefit in primary sclerosing cholangitis (PSC). Colchicine has been observed to reduce mortality in primary biliary cirrhosis in one study. The aim of this study was to examine the effect of colchicine in PSC.
Eighty-four patients with PSC were randomized to receive 1 mg of colchicine daily (n = 44) or placebo (n = 40) in a double-blind 3-year study. The effect of treatment was evaluated through blind scoring of 10 variables in prestudy and poststudy liver biopsy specimens, daily recording of symptoms, and biochemical tests (serum bilirubin, alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase, albumin, immunoglobulins, ceruloplasmin, alpha 1-antitrypsin, and plasma prothrombin levels) at 6-month intervals.
There was no evidence of a favorable effect of colchicine on survival, symptoms, serum biochemistry, or liver histology in patients with PSC.
One milligram of colchicine daily is ineffective in PSC.
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