Okanoue Takeshi, Sakamoto Michiie, Harada Kenichi, Inagaki Masaya, Totsuka Naoko, Hashimoto Gaia, Kumada Hiromitsu
Department of Gastroenterology, Saiseikai Suita Hospital, Osaka, Japan.
Department of Pathology, Keio University School of Medicine, Tokyo, Japan.
Hepatol Res. 2021 Sep;51(9):943-956. doi: 10.1111/hepr.13695. Epub 2021 Aug 5.
To evaluate the efficacy, safety, and tolerability of apararenone 10 mg/day in patients with nonalcoholic steatohepatitis (NASH).
In this multicenter, randomized, double-blind, placebo-controlled phase II study, patients received apararenone 10 mg or placebo once daily for 72 weeks. The primary efficacy end-point was percent change in serum alanine aminotransferase (ALT) from baseline to 24 weeks after randomization. Secondary efficacy end-points included changes in liver fibrosis markers. Adverse drug reactions (ADRs) and serum potassium levels were evaluated.
Forty-eight patients were randomly assigned to treatment (placebo, 23; apararenone, 25). The percent change in ALT at 24 weeks was -3.0% and -13.7% with placebo and apararenone, respectively (p = 0.308). The apararenone group showed greater reductions from baseline in fibrosis markers (type IV collagen 7S and procollagen-3 N-terminal peptide) and noninvasive tests of fibrosis (enhanced liver fibrosis score and Fibrosis-4 index) at all time points versus placebo. The percentage of patients with improvement of 1 point or more in fibrosis stage/without nonalcoholic fatty liver disease activity score worsening was 41.7% with apararenone and 26.1% with placebo (p = 0.203). Adverse drug reactions were reported in three (13.0%) and three (12.5%) patients in the placebo and apararenone groups, respectively. Serum potassium levels increased in the apararenone group during the study and decreased to near baseline after the end of treatment.
In patients with NASH, apararenone 10 mg/day for 72 weeks was effective in decreasing ALT levels, improved multiple potential fibrosis markers, and was safe and well tolerated. Pathological findings showed anti-inflammatory and antifibrotic effects of apararenone.
评估每天服用10毫克阿帕雷酮对非酒精性脂肪性肝炎（NASH）患者的疗效、安全性和耐受性。
在这项多中心、随机、双盲、安慰剂对照的II期研究中，患者每天接受一次10毫克阿帕雷酮或安慰剂治疗，持续72周。主要疗效终点是随机分组后24周血清丙氨酸氨基转移酶（ALT）相对于基线的变化百分比。次要疗效终点包括肝纤维化标志物的变化。评估药物不良反应（ADR）和血清钾水平。
48名患者被随机分配接受治疗（安慰剂组23名；阿帕雷酮组25名）。安慰剂组和阿帕雷酮组在24周时ALT的变化百分比分别为-3.0%和-13.7%（p = 0.308）。在所有时间点，与安慰剂相比，阿帕雷酮组的纤维化标志物（IV型胶原7S和前胶原-3 N末端肽）和纤维化的非侵入性检测（增强肝纤维化评分和纤维化-4指数）从基线的降低幅度更大。纤维化阶段改善1分或更多且非酒精性脂肪性肝病活动评分未恶化的患者百分比，阿帕雷酮组为41.7%，安慰剂组为26.1%（p = 0.203）。安慰剂组和阿帕雷酮组分别有3名（13.0%）和3名（12.5%）患者报告了药物不良反应。在研究期间，阿帕雷酮组血清钾水平升高，治疗结束后降至接近基线水平。
对于NASH患者，每天服用10毫克阿帕雷酮，持续72周，可有效降低ALT水平，改善多种潜在纤维化标志物，且安全耐受性良好。病理结果显示阿帕雷酮具有抗炎和抗纤维化作用。
