ISSN:
1365-2036
Source:
Blackwell Publishing Journal Backfiles 1879-2005
Topics:
Medicine
Notes:
Background : Tumour necrosis factor-α is thought to be important in the pathogenesis of portal hypertension. Oxpentifylline (pentoxifylline) and thalidomide inhibit endotoxin-induced tumour necrosis factor-α production in vitro.Aims : To assess the toxicity of oxpentifylline (pentoxifylline) and thalidomide in cirrhosis and their effect on the hepatic venous pressure gradient and tumour necrosis factor-α production.Methods : In an open-label pilot study, 20 abstinent patients with stable alcoholic cirrhosis and oesophageal varices were recruited; 12 patients completed haemodynamic measurements before and after treatment with oxpentifylline (pentoxifylline) 1800 mg (n = 6) or thalidomide 200 mg (n = 6) daily for 2 weeks. Tumour necrosis factor-α production was assessed in ex vivo monocyte cultures stimulated with endotoxin.Results : Thalidomide reduced the hepatic venous pressure gradient from 19.7 mmHg (9.3–23.5 mmHg) to 12.2 mmHg (4.7–19.5 mmHg) (P = 0.03) without reducing the hepatic blood flow or altering systemic haemodynamic parameters. Thalidomide reduced ex vivo tumour necrosis factor-α production by approximately 50%. Oxpentifylline (pentoxifylline) had no significant effect on any of the parameters measured. Side-effects led to dose reduction or treatment withdrawal in 40% of patients.Conclusion : Thalidomide, but not oxpentifylline (pentoxifylline), reduces the hepatic venous pressure gradient in stable alcoholic cirrhotics, an effect that may be mediated by the inhibition of tumour necrosis factor-α production. The role of tumour necrosis factor-α inhibitory drugs in the therapy of portal hypertension should be investigated in a randomized controlled trial.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1046/j.1365-2036.2003.01809.x
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