Division of Pediatric Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Emory University School of Medicine, Children's Healthcare of Atlanta, Atlanta, Georgia, USA.
Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA.
Hepatology. 2022 Aug;76(2):429-444. doi: 10.1002/hep.32403. Epub 2022 Feb 28.
To date, no pharmacotherapy exists for pediatric NAFLD. Losartan, an angiotensin II receptor blocker, has been proposed as a treatment due to its antifibrotic effects.
The Nonalcoholic Steatohepatitis Clinical Research Network conducted a multicenter, double-masked, placebo-controlled, randomized clinical trial in children with histologically confirmed NAFLD at 10 sites (September 2018 to April 2020). Inclusion criteria were age 8-17 years, histologic NAFLD activity score ≥ 3, and serum alanine aminotransferase (ALT) ≥ 50 U/l. Children received 100 mg of losartan or placebo orally once daily for 24 weeks. The primary outcome was change in ALT levels from baseline to 24 weeks, and the preset sample size was n = 110. Treatment effects were assessed using linear regression of change in treatment group adjusted for baseline value. Eighty-three participants (81% male, 80% Hispanic) were randomized to losartan (n = 43) or placebo (n = 40). During an enrollment pause, necessitated by the 2019 coronavirus pandemic, an unplanned interim analysis showed low probability (7%) of significant group difference. The Data and Safety Monitoring Board recommended early study termination. Baseline characteristics were similar between groups. The 24-week change in ALT did not differ significantly between losartan versus placebo groups (adjusted mean difference: 1.1 U/l; 95% CI = -30.6, 32.7; p = 0.95), although alkaline phosphatase decreased significantly in the losartan group (adjusted mean difference: -23.4 U/l; 95% CI = -41.5, -5.3; p = 0.01). Systolic blood pressure decreased in the losartan group but increased in placebo (adjusted mean difference: -7.5 mm Hg; 95% CI = -12.2, -2.8; p = 0.002). Compliance by pill counts and numbers and types of adverse events did not differ by group.
Losartan did not significantly reduce ALT in children with NAFLD when compared with placebo.
迄今为止，尚无针对小儿非酒精性脂肪性肝病 (NAFLD) 的药物治疗方法。血管紧张素 II 受体阻滞剂氯沙坦因其抗纤维化作用而被提议作为一种治疗方法。
非酒精性脂肪性肝炎临床研究网络 (Nonalcoholic Steatohepatitis Clinical Research Network) 在 10 个地点（2018 年 9 月至 2020 年 4 月）对组织学确诊为 NAFLD 的儿童进行了一项多中心、双盲、安慰剂对照、随机临床试验。纳入标准为年龄 8-17 岁，组织学 NAFLD 活动评分≥3，血清丙氨酸氨基转移酶 (ALT)≥50 U/l。儿童每天口服 100 mg 氯沙坦或安慰剂，持续 24 周。主要结局为从基线到 24 周时 ALT 水平的变化，预设样本量为 n=110。采用线性回归分析治疗组调整基线值后的变化来评估治疗效果。83 名参与者（81%为男性，80%为西班牙裔）被随机分配至氯沙坦（n=43）或安慰剂（n=40）组。由于 2019 年冠状病毒病大流行，需要暂停入组，计划外的中期分析显示组间差异的可能性很低（7%）。数据和安全监测委员会建议提前终止研究。两组的基线特征相似。氯沙坦组与安慰剂组 24 周时 ALT 的变化无显著差异（调整平均差值：1.1 U/l；95%CI=-30.6,32.7；p=0.95），但氯沙坦组碱性磷酸酶显著下降（调整平均差值：-23.4 U/l；95%CI=-41.5,-5.3；p=0.01）。氯沙坦组收缩压下降，而安慰剂组上升（调整平均差值：-7.5 mmHg；95%CI=-12.2,-2.8；p=0.002）。按药片计数和不良事件的数量和类型计算，两组的依从性无差异。
与安慰剂相比，氯沙坦并未显著降低小儿非酒精性脂肪性肝病患者的 ALT。
