Department of Gastroenterology and Hepatology, Dr Ziauddin Hospital, Clifton Campus, Karachi, Pakistan
Department of Gastroenterology and Hepatology, Dr Ziauddin Hospital, Clifton Campus, Karachi, Pakistan.
BMJ Open Gastroenterol. 2024 Jun 6;11(1):e001342. doi: 10.1136/bmjgast-2023-001342.
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.
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.
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.
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.
NCT05804305.
非酒精性脂肪性肝炎（NASH）的治疗是一个未满足的临床需求。米索前列醇是一种天然前列腺素 E1 的结构类似物，据报道可减少促炎细胞因子的产生，可能在治疗 NASH 方面具有潜在作用。我们旨在评估米索前列醇治疗 NASH 患者的疗效和安全性。
在这项 2 期、双盲、随机、安慰剂对照试验中，NASH 患者以 1:1 的比例随机分配接受 200µg 米索前列醇或安慰剂，每日 3 次，持续 2 个月。主要终点是改善肝功能试验（LFTs）、白细胞介素 6（IL-6）和内毒素水平。次要终点是改善胰岛素抵抗、血脂异常、肝纤维化和肝脂肪变性。
共有 50 名患者接受了随机分组，其中 44 名（88%）为男性。年龄范围为 25-64 岁（平均值±平均值标准差（SEM）38.1±1.4）。19 名（38%）患者同时患有 2 型糖尿病。32 名（64%）患者超重或肥胖。在 2 个月的治疗结束时，米索前列醇组的总白细胞计数（TLC）（p=0.005）、丙氨酸氨基转移酶（ALT）（p<0.001）、天冬氨酸氨基转移酶（AST）（p=0.002）和受控衰减参数（CAP）（p=0.003）均有所下降，而安慰剂组的 ALT（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）均有所下降。两组的胰岛素抵抗、肝纤维化（弹性成像）和血脂异常均无改善。然而，与安慰剂组相比，米索前列醇组的 CAP 显著降低（p=0.039）。此外，米索前列醇组治疗前后的 IL-6 和内毒素水平保持稳定，而安慰剂组的 IL-6 水平升高（p=0.049）。米索前列醇组有 6 名（12%）患者至少有 1 种不良事件，安慰剂组有 5 名（10%）患者有不良事件。米索前列醇组最常见的不良事件是腹泻。每组均未发生危及生命的事件或与治疗相关的死亡。
米索前列醇和安慰剂组的生化谱均有改善，但 CAP 所示的脂肪变性改善更明显，而安慰剂组的 IL-6 水平恶化。
NCT05804305。
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