A pilot study to investigate the use of oxpentifylline (pentoxifylline) and thalidomide in portal hypertension secondary to alcoholic cirrhosis
Summary 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...
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Published in | Alimentary pharmacology & therapeutics Vol. 19; no. 1; pp. 79 - 88 |
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Main Authors | , , , , |
Format | Journal Article |
Language | English |
Published |
Oxford, UK
Blackwell Science Ltd
01.01.2004
Blackwell |
Subjects | |
Online Access | Get full text |
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Summary: | Summary
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. |
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ISSN: | 0269-2813 1365-2036 |
DOI: | 10.1046/j.1365-2036.2003.01809.x |