A pilot study to investigate the use of oxpentifylline (pentoxifylline) and thalidomide in portal hypertension secondary to alcoholic cirrhosis

• Published in: Alimentary pharmacology & therapeutics Vol. 19; no. 1; pp. 79 - 88
• Main Authors: Austin, A. S., Mahida, Y. R., Clarke, D., Ryder, S. D., Freeman, J. G.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Science Ltd 01.01.2004; Blackwell
• Subjects: Adult; Aged; Biological and medical sciences; Blood Pressure - drug effects; Cardiac Output - drug effects; Digestive system; Drug Therapy, Combination; Enzyme Inhibitors - adverse effects; Enzyme Inhibitors - therapeutic use; Female; Gastroenterology. Liver. Pancreas. Abdomen; Humans; Hypertension, Portal - drug therapy; Hypertension, Portal - etiology; Hypertension, Portal - metabolism; Liver Cirrhosis, Alcoholic - complications; Liver Cirrhosis, Alcoholic - metabolism; Male; Medical sciences; Middle Aged; Pentoxifylline - adverse effects; Pentoxifylline - therapeutic use; Pharmacology. Drug treatments; Pilot Projects; Thalidomide - adverse effects; Thalidomide - therapeutic use; Tumor Necrosis Factor-alpha - metabolism; Vasodilator Agents - adverse effects; Vasodilator Agents - therapeutic use; 3',5'-Cyclic-nucleotide phosphodiesterase; Antileprous agent; Vasodilator agent; Portal circulation disease; Enzyme; Enzyme inhibitor; Cardiovascular disease; Hepatic disease; Hypnotic; Esterases; Phosphoric diester hydrolases; Vascular disease; Pentoxifylline; Cirrhosis; Portal hypertension; Digestive diseases; Hydrolases; Xanthine derivatives; Sedative; Antibacterial agent; Thalidomide
• ISSN: 0269-2813; 1365-2036
• DOI: 10.1046/j.1365-2036.2003.01809.x

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.