Department of Gastroenterology and Hepatology, Digestive Disease Institute, Cleveland Clinic, Cleveland, OH 44915, USA.
Hepatology. 2011 Nov;54(5):1610-9. doi: 10.1002/hep.24544. Epub 2011 Aug 24.
The primary aim of this study was to compare the effects of pentoxifylline (PTX) versus placebo on the histological features of nonalcoholic steatohepatitis (NASH). In all, 55 adults with biopsy-confirmed NASH were randomized to receive PTX at a dose of 400 mg three times a day (n = 26) or placebo (n = 29) over 1 year. The primary efficacy endpoint was defined as improvement in histological features of NASH through reduction in steatosis, lobular inflammation, and/or hepatocellular ballooning as reflected by a decrease of ≥ 2 points in the nonalcoholic fatty liver disease (NAFLD) activity score (NAS). After 1 year, intention-to-treat analysis showed a decrease of ≥ 2 points in the NAS in 38.5% of patients on PTX versus 13.8% of those on placebo (P = 0.036). Per protocol analysis, a decrease of ≥ 2 points in the NAS from baseline was observed in 50% of the patients on PTX versus 15.4% of those on placebo (P = 0.01). The mean change in NAS score from baseline was -1.6 in the PTX group, versus -0.1 in the placebo group (P < 0.001). PTX significantly improved steatosis (mean change in score -0.9 versus -0.04 with placebo, P < 0.001) and lobular inflammation (median change -1 versus 0 with placebo, P = 0.02). No significant effects in hepatocellular ballooning were observed. PTX also improved liver fibrosis (mean change in fibrosis score was -0.2 among those on PTX versus +0.4 among those on placebo, P = 0.038). Although not statistically significant (P = 0.17), improvement in fibrosis was observed in a greater proportion (35%) of patients in the PTX group compared to placebo (15%). Adverse effects were similar in both groups.
PTX improved histological features of NASH compared to placebo. PTX was well tolerated in patients with NASH.
本研究旨在比较己酮可可碱（PTX）与安慰剂对非酒精性脂肪性肝炎（NASH）组织学特征的影响。
共纳入 55 例经肝活检证实的 NASH 患者，随机分为 PTX 组（n=26）和安慰剂组（n=29），PTX 组予 PTX 400mg，每日 3 次，安慰剂组予安慰剂，两组疗程均为 1 年。主要疗效终点定义为通过减少脂肪变性、小叶炎症和/或肝细胞气球样变来改善 NASH 的组织学特征，即非酒精性脂肪性肝病（NAFLD）活动评分（NAS）降低≥2 分。
1 年后，意向治疗分析显示，PTX 组患者 NAS 降低≥2 分的比例为 38.5%，安慰剂组为 13.8%（P=0.036）。按方案分析，PTX 组患者 NAS 基线降低≥2 分的比例为 50%，安慰剂组为 15.4%（P=0.01）。PTX 组和安慰剂组患者 NAS 评分的平均变化分别为-1.6 和-0.1（P<0.001）。PTX 可显著改善脂肪变性（评分变化-0.9 与安慰剂组-0.04，P<0.001）和小叶炎症（中位数变化-1 与安慰剂组 0，P=0.02）。未观察到肝细胞气球样变的显著改善。PTX 还可改善肝纤维化（PTX 组纤维化评分的平均变化为-0.2，安慰剂组为+0.4，P=0.038）。虽然无统计学意义（P=0.17），但与安慰剂组相比，PTX 组改善纤维化的患者比例更高（35%比 15%）。两组不良反应相似。
与安慰剂相比，PTX 可改善 NASH 的组织学特征。PTX 治疗 NASH 患者耐受性良好。
