Emricasan改善肝硬化，高MELD患者的肝功能

StephenW

Emricasan improves liver function in patients with cirrhosis, high MELD

Frenette CT, et al. Clin Gastroenterol Hepatol. 2018;doi:10.1016/j.cgh.06.012.
July 31, 2018

Compared with placebo, treatment with emricasan for 3 months reduced MELD scores, international normalized ratio and total bilirubin in patients with cirrhosis and MELD score 15 or higher, according to a recently published study.

“This study is a proof of concept study for this medication which may potentially reverse and stabilize decompensated cirrhosis in patients with MELD scores between 15 and 20,” Catherine T. Frenette, MD, from the Scripps Clinic in California, told Healio Gastroenterology and Liver Disease. “If this is proven to be of benefit in larger studies, then it may be an option for patients to delay the need for liver transplant, or to help those patients who cannot get a liver transplant.”
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Frenette and colleagues enrolled patients with Child-Pugh class A or B cirrhosis and MELD scores between 11 and 18 to participate in the study. The researchers randomly assigned 42 patients to receive emricasan (Conatus Pharmaceuticals) and 44 patients to receive placebo.

Most of the patients were decompensated (90.7%), including variceal hemorrhage (12.8%), ascites (52.3%) and hepatic encephalopathy (68.6%).

While the researchers observed no significant difference in total bilirubin, INR or serum albumin between the groups’ overall populations at 3 months, patients with MELD scores of 15 or higher showed improvement in total bilirubin (–0.79 mg/dL; P < .05) and INR (–0.19; P < .05) compared with placebo. Patients with nonalcoholic steatohepatitis showed a nonsignificant trend toward similar improvements.

Both patients with MELD scores of 15 or higher (P = .003) and patients with NASH (P = .029) had significant improvements in MELD scores at 3 months compared with placebo.

At 6 months, the researchers compared patients in the emricasan group with their baseline results and found that those in the high-MELD subgroup either stabilized or continued to show improvements for MELD score (–1.6 to –2.8) and INR (–0.14 to –0.21). The NASH subgroup also showed stabilized or relative improvements over a total of 6 months.

The rates of moderate adverse events (38.6% vs. 28.6%), severe adverse events (11.4% vs. 9.5%) and discontinuations due to adverse events (6.8% vs. 4.8%) were similar between the treatment and placebo groups, with no reported deaths.

“The results need to be proven in a larger phase 3 study, but with these results I am hopeful that we will soon have a treatment for these patients.,” Frenette said. – by Talitha Bennett

Disclosure: Frenette reports she is consultant to Bayer, BTG, Conatus, Gilead, Intercept and Wako; an advisory board member of Eisai; a member of the speakers bureau for AbbVie, Bayer, Bristol-Myers Squibb, Gilead, Intercept, Merck and Salix; and receives research support from Bayer, Conatus and Genfit. Please see the full study for the other authors' relevant financial disclosures.

StephenW

Emricasan改善肝硬化，高MELD患者的肝功能

Frenette CT，et al。 Clin Gastroenterol Hepatol。 2018; DOI：10.1016 / j.cgh.06.012。
2018年7月31日

根据最近发表的一项研究，与安慰剂相比，用emricasan治疗3个月可降低肝硬化患者的MELD评分，国际标准化比率和总胆红素，且MELD评分为15分或更高。

加利福尼亚斯克里普斯诊所的Catherine T. Frenette博士告诉Healio Gastroenterology and Liver，“这项研究证明了这种药物的概念研究，可能会使MELD评分在15到20之间的患者反转并稳定失代偿性肝硬化”。疾病。 “如果这被证明对大型研究有益，那么患者可能会选择延迟肝移植的需要，或者帮助那些无法进行肝移植的患者。”
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Frenette及其同事招募患有Child-Pugh A级或B级肝硬化且MELD评分在11到18之间的患者参与该研究。研究人员随机分配了42名接受emricasan（Conatus Pharmaceuticals）的患者和44名接受安慰剂的患者。

大多数患者失代偿（90.7％），包括静脉曲张出血（12.8％），腹水（52.3％）和肝性脑病（68.6％）。

虽然研究人员观察到3个月时各组总体人群中总胆红素，INR或血清白蛋白无显着差异，但MELD评分为15或更高的患者总胆红素改善（-0.79 mg / dL; P <.05）与安慰剂相比，INR（-0.19; P <.05）。患有非酒精性脂肪性肝炎的患者表现出类似改善的无显着趋势。

MELD评分为15或更高（P = .003）的患者和患有NASH的患者（P = .029）与安慰剂相比，3个月时MELD评分显着改善。

在6个月时，研究人员将emricasan组的患者与基线结果进行了比较，发现高MELD亚组的患者稳定或继续显示MELD评分（-1.6至-2.8）和INR（-0.14至 - ）的改善。 0.21）。 NASH亚组在总共6个月内也表现出稳定或相对改善。

治疗组和安慰剂组之间的中度不良事件发生率（38.6％vs。28.6％），严重不良事件（11.4％vs。9.5％）和不良事件中断（6.8％vs。4.8％）相似，没有报告死亡。

“结果需要在更大的3期研究中得到证实，但有了这些结果，我希望我们很快就会对这些患者进行治疗。”Frenette说。 - Talitha Bennett

披露：Frenette报道她是Bayer，BTG，Conatus，Gilead，Intercept和Wako的顾问; Eisai的顾问委员会成员; AbbVie，Bayer，Bristol-Myers Squibb，Gilead，Intercept，Merck和Salix的演讲局成员;并获得拜耳，Conatus和Genfit的研究支持。有关其他作者的相关财务披露，请参阅完整的研究。