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新型NASH治疗可减少肝脏脂肪,改善肝损伤标记

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发表于 2017-4-26 23:32 |显示全部帖子
Novel NASH treatment reduces hepatic fat, improves liver injury markers
April 22, 2017

AMSTERDAM — A pegylated form of the hormone FGF21 injected subcutaneously produced improvements in hepatic fat, fibrosis markers and metabolic parameters, according to data presented at the International Liver Congress.


“BMS-986036 10 mg daily and 20 mg weekly for 16 weeks, compared with placebo, significantly decreased hepatic fat fraction in patients with NASH and fibrosis 1 through 3,” Arun Sanyal, MD, from Virginia Commonwealth University, said during his late breaker presentation. “BMS-986036 daily and weekly — relative to placebo — was associated with improvements in biomarkers of fibrosis, metabolic parameters and markers of hepatic injury.”

Sanyal and colleagues conducted a multicenter, randomized, double-blind, placebo-controlled, proof-of-concept study using BMS-986036 (Bristol-Myers Squibb). They recruited adults with BMI 25 kg/mg2 or greater, NASH as confirmed by biopsy and hepatic fat fraction at 10% or greater as determined by MRI-proton density fat fraction (MRI-PDFF).

After a 1-week lead-in placebo period to ensure compliance with injections, patients received injections of either of BMS-986036 10 mg daily (n = 23), 20 mg weekly (n = 21) or placebo daily (n = 24) for 16 weeks. At baseline, all groups were similarly matched.

At week 16, both BMS-986036 groups showed reduced hepatic fat fraction; the 10-mg group saw a 6.8% reduction (P = .0004 compared to placebo) while the 20-mg group saw a 5.2% reduction (P = .008 compared to placebo).

“A relative reduction of 29% or greater in MRI-PDFF produced a histologic response in NASH patients,” Sanyal said.

In comparison to placebo, where 25% of patients reached that 30% relative reduction threshold, 57% of patients receiving 10 mg (P = 0.279) and 52% of patients receiving 20 mg (P = .0566) of the study drug met the same endpoint.

When looking at adiponectin, Sanyal reported that the placebo group saw a –2.3% change, while the BMS-986036 10 mg group saw a 15.3% increase (P = .0071) and the 20-mg group saw a 15.9% increase (P = .0072). Similarly, triglycerides, LDL and HDL cholesterol improved in the treatment groups but failed to improve with placebo.

Over the course of the study, improvements occurred with regard to enzymes alanine aminotransferase and aspartate aminotransferase in the treatment groups but not in the placebo group.

Using MR elastography (MRE), Sanyal showed categorical improvement in liver stiffness. Just seven patients in the placebo group experienced a 15% or greater reduction in liver stiffness while BMS-986036 10 mg achieved the same goal in 36% of patients and 33% of the 20 mg group reported the same.

There were no serious adverse events in any of the treatment groups and most adverse events were considered mild.

“These results suggest that the compound has beneficial effects on steatosis, liver injury and fibrosis in NASH,” Sanyal said. – by Katrina Altersitz

Reference s :

Sanyal A. LBO-02. Presented at: International Liver Congress; April 19-24, 2017; Amsterdam.

Disclosure: This study was supported by Bristol-Myers Squibb.

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发表于 2017-4-26 23:32 |显示全部帖子
新型NASH治疗可减少肝脏脂肪,改善肝损伤标记
2017年4月22日

AMSTERDAM - 根据国际肝脏大会提供的数据,激素FGF21的聚乙二醇化形式皮下注射产生肝脂肪,纤维化标志物和代谢参数的改善。


弗吉尼亚联邦大学的Arun Sanyal医学博士说:“BMS-986036每日10mg,每周20mg,持续16周,与安慰剂相比,NASH和纤维化1〜3患者的肝脂肪分数显着降低。介绍。 “BMS-986036每日和每周 - 相对于安慰剂 - 与纤维化,代谢参数和肝损伤标志物的生物标志物的改善有关。

Sanyal及其同事使用BMS-986036(Bristol-Myers Squibb)进行了一项多中心,随机,双盲,安慰剂对照的概念验证研究。他们招募BMI 25 kg / mg2或更高的成年人,NASH通过活检证实,肝脏脂肪分数为10%或更大,通过MRI-质子密度脂肪分数(MRI-PDFF)测定。

经过1周的安慰剂周期以确保注射顺利进行,患者每天接受BMS-986036 10mg(n = 23),每周20mg(n = 21)或每日安慰剂(n = 24) 16周。在基线时,所有组均相似。

在第16周,两组BMS-986036组均显示肝脏脂肪分数降低; 10 mg组与安慰剂组相比,减少了6.8%(P = 0.0004),而20 mg组与安慰剂组相比减少了5.2%(P = 0.008)。

“在MRI-PDFF中相对减少29%以上可以在NASH患者中产生组织学反应,”Sanyal说。

与安慰剂相比,其中25%的患者达到相对降低阈值的30%,接受10mg(P = 0.279)的患者中有57%和接受20 mg(P = 0.0566)研究药物的患者达到了相同的终点。

当查看脂联素时,Sanyal报道安慰剂组的变化为-2.3%,而BMS-986036 10 mg组增加了15.3%(P = .0071),20 mg组增加了15.9%(P = .0072)。类似地,甘油三酸酯,LDL和HDL胆固醇在治疗组中改善,但是与安慰剂不能改善。

在研究过程中,治疗组中丙氨酸氨基转移酶和天冬氨酸氨基转移酶的改善发生在治疗组中,但不是安慰剂组。

使用MR弹性成像(MRE),Sanyal显示出肝硬化的明显改善。安慰剂组中只有7名患者的肝硬化减少了15%或更多,而BMS-986036 10 mg在36%的患者中达到相同的目标,而在20 mg组中有33%报告相同。

任何治疗组均未发生严重不良事件,多数不良事件被认为是轻度的。

“这些结果表明该化合物对NASH的脂肪变性,肝损伤和纤维化有有益作用,”Sanyal说。 - 由Katrina Altersitz

参考文献:

Sanyal A. LBO-02。主讲:国际肝会; 2017年4月19日至24日阿姆斯特丹

披露:本研究得到了Bristol-Myers Squibb的支持。
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