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Resmetirom可有效治疗非酒精性脂肪性肝炎
作者:小柯机器人 发布时间:2019/11/13 15:54:02

英国牛津大学Stephen A Harrison团队在研究中取得进展。他们的最新研究提出Resmetirom可治疗非酒精性脂肪性肝炎。2019年11月11日,国际知名学术期刊《柳叶刀》发表了这一成果。

非酒精性脂肪性肝炎(NASH)的特征是肝脏脂肪变性、炎症、肝细胞损伤和进行性肝纤维化。Resmetirom(MGL-3196)是一种肝脏靶向、口服活性、选择性的甲状腺激素-β受体激动剂,旨在通过增加肝脏脂肪代谢和降低脂毒性来改善NASH。

研究组在美国25个中心进行了这项为期36周的随机、双盲、安慰剂对照研究,招募了125名经活检证实的成人NASH患者,纤维化1-3期,基线肝脏脂肪至少为10%。将其按2:1随机分组,84名每日口服一次Resmetirom 80mg,41名每日口服一次安慰剂。

治疗12周时,Resmetirom组的肝脏脂肪减少了32.9%,安慰剂组减少了10.4%;第36周时,Resmetirom组的肝脏脂肪减少了37.3%,安慰剂组减少了8.5%,差异均具有统计学意义。不良反应多为轻中度,两组间发生率相差不大。但Resmetirom组中短暂性轻度腹泻和恶心较常见。

总之,Resmetirom治疗NASH患者12周和36周时肝脏脂肪显著减少。该研究样本有限,需扩充患者来进一步验证Resmetirom的安全性和有效性。

附:英文原文

Title: Resmetirom (MGL-3196) for the treatment of non-alcoholic steatohepatitis: a multicentre, randomised, double-blind, placebo-controlled, phase 2 trial

Author: Stephen A Harrison, Mustafa R Bashir, Cynthia D Guy, Rong Zhou, Cynthia A Moylan, Juan P Frias, Naim Alkhouri, Meena B Bansal, Seth Baum, Brent A Neuschwander-Tetri, Rebecca Taub, Sam E Moussa

Issue&Volume: November 11, 2019

Abstract:

Background

Non-alcoholic steatohepatitis (NASH) is characterised by hepatic steatosis, inflammation, hepatocellular injury, and progressive liver fibrosis. Resmetirom (MGL-3196) is a liver-directed, orally active, selective thyroid hormone receptor-β agonist designed to improve NASH by increasing hepatic fat metabolism and reducing lipotoxicity. We aimed to assess the safety and efficacy of resmetirom in patients with NASH.

Methods

MGL-3196-05 was a 36-week randomised, double-blind, placebo-controlled study at 25 centres in the USA. Adults with biopsy confirmed NASH (fibrosis stages 1–3) and hepatic fat fraction of at least 10% at baseline when assessed by MRI-proton density fat fraction (MRI-PDFF) were eligible. Patients were randomly assigned 2:1 by a computer-based system to receive resmetirom 80 mg or matching placebo, orally once a day. Serial hepatic fat measurements were obtained at weeks 12 and 36, and a second liver biopsy was obtained at week 36. The primary endpoint was relative change in MRI-PDFF assessed hepatic fat compared with placebo at week 12 in patients who had both a baseline and week 12 MRI-PDFF. This trial is registered with ClinicalTrials.gov, number NCT02912260.

Findings

348 patients were screened and 84 were randomly assigned to resmetirom and 41 to placebo at 18 sites in the USA. Resmetirom-treated patients (n=78) showed a relative reduction of hepatic fat compared with placebo (n=38) at week 12 (32·9% resmetirom vs 10·4% placebo; least squares mean difference 22·5%, 95% CI 32·9 to 12·2; p<0·0001) and week 36 (37·3% resmetirom [n=74] vs 8·5 placebo [n=34]; 28·8%, 42·0 to 15·7; p<0·0001). Adverse events were mostly mild or moderate and were balanced between groups, except for a higher incidence of transient mild diarrhoea and nausea with resmetirom.

Interpretation

Resmetirom treatment resulted in significant reduction in hepatic fat after 12 weeks and 36 weeks of treatment in patients with NASH. Further studies of resmetirom will allow assessment of safety and effectiveness of resmetirom in a larger number of patients with NASH with the possibility of documenting associations between histological effects and changes in non-invasive markers and imaging.

DOI: 10.1016/S0140-6736(19)32517-6

Source: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(19)32517-6/fulltext

期刊信息

LANCET:《柳叶刀》,创刊于1823年。隶属于爱思唯尔出版社,最新IF:59.102
官方网址:http://www.thelancet.com/
投稿链接:http://ees.elsevier.com/thelancet