背景:非酒精性脂肪性肝炎(NASH)的管理是一个未满足的临床需求。米索前列醇,前列腺素E1是天然存在的前列腺素E1的结构类似物,据报道可以减少促炎细胞因子的产生,并且可能在治疗NASH中具有潜在作用。我们旨在评估米索前列醇治疗NASH患者的疗效和安全性。
方法:在此阶段2,双盲,随机化,安慰剂对照试验,NASH患者以1∶1的比例随机分组,接受200µg米索前列醇或安慰剂,每日3次,共2个月.主要终点是肝功能测试(LFTs)的改善,白细胞介素-6(IL-6)和内毒素水平。次要终点是胰岛素抵抗的改善,血脂异常,肝纤维化和肝脂肪变性。
结果:共有50名患者接受了随机分组,其中44人(88%)为男性。年龄范围为25-64岁(平均值±SE(SEM)38.1±1.4)。19例(38%)患者合并2型糖尿病。32例(64%)患者超重或肥胖。在2个月的治疗结束时,总白细胞计数(TLC)减少(p=0.005),丙氨酸氨基转移酶(ALT)(p<0.001),谷草转氨酶(AST)(p=0.002)和受控衰减参数(CAP)(p=0.003)在米索前列醇组中观察到,而安慰剂随后ALT下降(p<0.001),AST(p=0.018),γ-谷氨酰转移酶(GGT)(p=0.003),CAP(p=0.010)和甘油三酯(p=0.048)。胰岛素抵抗没有减少,两组的肝纤维化(弹性成像)和血脂异常。然而,与安慰剂组相比,米索前列醇导致CAP显著降低(p=0.039)。此外,在米索前列醇组中,治疗前和治疗后IL-6和内毒素水平保持稳定,而在安慰剂组,IL-6水平升高(p=0.049).米索前列醇组有6例(12%)患者出现至少1例不良事件,安慰剂组中有5例(10%)。米索前列醇组最常见的不良事件是腹泻。各组均未发生危及生命事件或治疗相关死亡。
结论:米索前列醇和安慰剂组的生化特征均有改善,无统计学意义。然而,脂肪变性有了更多的改善,正如CAP所描绘的,米索前列醇组和安慰剂组IL-6水平恶化。
背景:NCT05804305。
BACKGROUND: The management of non-alcoholic steatohepatitis (NASH) is an unmet clinical need.
Misoprostol, a structural analogue of naturally occurring prostaglandin E1, has been reported to decrease proinflammatory cytokine production and may have a potential role in treating NASH. We aimed to evaluate the efficacy and safety of
misoprostol in treating patients with NASH.
METHODS: In this phase 2, double-blind, randomised, placebo-controlled trial, patients with NASH were randomly assigned in a 1:1 ratio to receive 200 µg of misoprostol or placebo thrice daily for 2 months. The primary endpoint was an improvement in liver function tests (LFTs), interleukin-6 (IL-6) and endotoxin levels. The secondary endpoint was improvement in insulin resistance, dyslipidaemia, hepatic fibrosis and hepatic steatosis.
RESULTS: A total of 50 patients underwent randomisation, of whom 44 (88%) were males. The age range was 25-64 years (mean±SE of mean (SEM) 38.1±1.4). 19 (38%) patients had concomitant type 2 diabetes mellitus. 32 (64%) patients were either overweight or obese. At the end of 2 months\' treatment, a reduction in total leucocyte count (TLC) (p=0.005), alanine aminotransferase (ALT) (p<0.001), aspartate aminotransferase (AST) (p=0.002) and controlled attenuation parameter (CAP) (p=0.003) was observed in the misoprostol group, whereas placebo ensued a decline in ALT (p<0.001), AST (p=0.018), gamma-glutamyl transferase (GGT) (p=0.003), CAP (p=0.010) and triglycerides (p=0.048). There was no diminution in insulin resistance, hepatic fibrosis (elastography) and dyslipidaemia in both groups. However,
misoprostol resulted in a significant reduction in CAP as compared with the placebo group (p=0.039). Moreover, in the misoprostol group, pretreatment and post-treatment IL-6 and endotoxin levels remained stable, while in the placebo group, an increase in the IL-6 levels was noted (p=0.049). Six (12%) patients had at least one adverse event in the
misoprostol group, as did five (10%) in the placebo group. The most common adverse event in the
misoprostol group was diarrhoea. No life-threatening events or treatment-related deaths occurred in each group.
CONCLUSIONS: Improvement in the biochemical profile was seen in both misoprostol and placebo groups without any statistically significant difference. However, there was more improvement in steatosis, as depicted by CAP, in the misoprostol group and worsening of IL-6 levels in the placebo group.
BACKGROUND: NCT05804305.