Austin A S, Mahida Y R, Clarke D, Ryder S D, Freeman J G
Division of Gastroenterology, University Hospital, Queens Medical Centre, Nottingham, UK.
Aliment Pharmacol Ther. 2004 Jan 1;19(1):79-88. doi: 10.1046/j.1365-2036.2003.01809.x.
Tumour necrosis factor-alpha is thought to be important in the pathogenesis of portal hypertension. Oxpentifylline (pentoxifylline) and thalidomide inhibit endotoxin-induced tumour necrosis factor-alpha production in vitro.
To assess the toxicity of oxpentifylline (pentoxifylline) and thalidomide in cirrhosis and their effect on the hepatic venous pressure gradient and tumour necrosis factor-alpha production.
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-alpha production was assessed in ex vivo monocyte cultures stimulated with endotoxin.
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-alpha 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.
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-alpha production. The role of tumour necrosis factor-alpha inhibitory drugs in the therapy of portal hypertension should be investigated in a randomized controlled trial.
肿瘤坏死因子-α被认为在门静脉高压的发病机制中起重要作用。己酮可可碱（戊氧苯茶碱）和沙利度胺在体外可抑制内毒素诱导的肿瘤坏死因子-α的产生。
评估己酮可可碱（戊氧苯茶碱）和沙利度胺在肝硬化患者中的毒性，以及它们对肝静脉压力梯度和肿瘤坏死因子-α产生的影响。
在一项开放标签的试点研究中，招募了20例戒酒的、患有稳定酒精性肝硬化和食管静脉曲张的患者；12例患者在接受每日1800毫克己酮可可碱（戊氧苯茶碱）（n = 6）或200毫克沙利度胺（n = 6）治疗2周前后完成了血流动力学测量。在用内毒素刺激的离体单核细胞培养物中评估肿瘤坏死因子-α的产生。
沙利度胺使肝静脉压力梯度从19.7 mmHg（9.3 - 23.5 mmHg）降至12.2 mmHg（4.7 - 19.5 mmHg）（P = 0.03），而未降低肝血流量或改变全身血流动力学参数。沙利度胺使离体肿瘤坏死因子-α的产生减少了约50%。己酮可可碱（戊氧苯茶碱）对所测量的任何参数均无显著影响。40%的患者因副作用导致剂量减少或停药。
沙利度胺而非己酮可可碱（戊氧苯茶碱）可降低稳定酒精性肝硬化患者的肝静脉压力梯度，这一作用可能是由抑制肿瘤坏死因子-α的产生介导的。应在随机对照试验中研究肿瘤坏死因子-α抑制药物在门静脉高压治疗中的作用。
