Pentoxifylline improves short-term survival in severe acute alcoholic hepatitis: A double-blind, placebo-controlled trial
Pentoxifylline improves short-term survival in severe acute alcoholic hepatitis: A double-blind, placebo-controlled trial
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DOI：
10.1053/gast.2000.20189
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发表时间：
2000-12-01
期刊：
影响因子：
29.4
通讯作者：
Shakil, O
中科院分区：
文献类型：
--
作者：
Akriviadis, E;Botla, R;Shakil, O
背景与目的：我们河流部早期的一项初步研究表明，肿瘤坏死因子的抑制剂己酮可可碱(PTX)对重症急性酒精性肝炎的治疗有好处。本研究的目的是在更大的患者队列中评估这种治疗方法。方法：101例重型酒精性肝炎患者(Maddrey判别因子大于或等于32)进入为期4周的随机双盲试验，PTX(400 mg，每日3次)与安慰剂对照。研究的主要终点是PTX对(1)短期存活率和(2)进展为肝肾综合征的影响。在随机化方面，两组在人口统计学和临床特征或实验室数值(包括肿瘤坏死因子)方面没有差异。结果：接受PTX治疗的49例患者中有12例(24.5%)和接受安慰剂治疗的52例患者中有24例(46.1%)在指数住院期间死亡(P=0.037；相对危险度0.59；95%可信区间0.35-0.97)。死亡原因分别为肝肾综合征6例(50%)和22例(91.7%)(P=0.009；相对危险度0.29；95%可信区间0.13~0.65)。三个变量(年龄、随机化的肌酐水平和PTX治疗)与存活率独立相关。随机分组的肿瘤坏死因子值不能预测存活期；然而，在研究期间，与两组存活者相比，死亡者的肿瘤坏死因子水平显著升高。结论：PTX治疗可提高重型酒精性肝炎患者的短期存活率。这一益处似乎与显著降低发展为肝肾综合征的风险有关。住院期间升高的肿瘤坏死因子水平与死亡率的增加有关。
Background & Aims:An earlier pilot study from our river unit suggested benefit from treatment with pentoxifylline (PTX), an inhibitor of tumor necrosis factor (TNF), in severe acute alcoholic hepatitis. The aim of the present study was to evaluate this treatment in a larger cohort of patients. Methods: One hundred one patients with severe alcoholic hepatitis (Maddrey discriminant factor greater than or equal to 32) entered a 4-week double-blind randomized trial of PTX (400 mg orally 3 times daily) vs, placebo. Primary endpoints of the study were the effect of PTX on (1) short-term survival and (2) progression to hepatorenal syndrome. On randomization, there were no differences in demographic and clinical characteristics or laboratory values (including TNF) between the 2 groups. Results: Twelve (24.5%) of the 49 patients who received PTX and 24 (46.1%) of the 52 patients who received placebo died during the index hospitalization (P = 0.037; relative risk, 0.59; 95% confidence interval, 0.35-0.97). Hepatorenal syndrome was the cause of death in 6 (50%) and 22 (91.7%) patients (P = 0.009; relative risk, 0.29; 95% confidence interval, 0.13-0.65). Three variables (age, creatinine level on randomization, and treatment with PTX) were independently associated with survival. TNF Values on randomization were not predictive of survival; however, during the study period they increased markedly in nonsurvivors compared with survivors in both groups. Conclusions: Treatment with PTX improves short-term survival in patients with severe alcoholic hepatitis. The benefit appears to be related to a significant decrease in the risk of developing hepatorenal syndrome. increasing TNF levels during the hospital course are associated with an increase in mortality rate.