Younossi Zobair M, Stepanova Maria, Racila Andrei, Henry Linda, Labriola Dominic, Taub Rebecca, Nader Fatema
The Global NASH Council, Washington, District of Columbia, USA.
Beatty Liver and Obesity Research Program, Inova Health System, Falls Church, Virginia, USA.
Hepatology. 2025 Apr 1;81(4):1318-1327. doi: 10.1097/HEP.0000000000001084. Epub 2024 Sep 6.
Resmetirom, liver-directed thyroid-hormone receptor-β agonist, received approval for metabolic dysfunction-associated steatohepatitis (MASH) treatment. We assessed health-related quality of life (HRQL) in patients with MASH treated with resmetirom.
Patients with MASH/NASH without cirrhosis and with confirmed/suspected fibrosis were enrolled in a 54-month double-blind randomized placebo-controlled phase III clinical trial with serial biopsy assessments at baseline and week 52 (MAESTRO-NASH, NCT03900429). HRQL was assessed using Chronic Liver Disease Questionnaire-NASH (CLDQ-NAFLD) and Liver Disease Quality of Life (LDQOL). Baseline HRQL score changes by treatment group (resmetirom 80 mg, resmetirom 100 mg, or placebo) and histological response (improvement of fibrosis without worsening of NAFLD activity score or resolution of MASH/NASH without worsening of fibrosis) were compared after 52 weeks. Included were 966 intention-to-treat patients: 323 received resmetirom 100 mg, 322 resmetirom 80 mg, and 321 placebo. By weeks 24 and 52, patients receiving 80 or 100 mg resmetirom experienced HRQL improvement in CLDQ-NAFLD Worry domain (mean +0.21 to +0.24, p < 0.05). At week 52, subjects who met histologic endpoints after treatment with resmetirom (100 mg and 80 mg pooled) experienced HRQL improvement in CLDQ-NAFLD Worry +0.46 (41% met minimal clinically important difference [MCID]), LDQOL domains: Role Emotional +3.0 (28% met MCID), Health Distress +8.1 (38% MCID), Stigma +3.5 (39% MCID), and total LDQOL +2.2 (35% MCID) (all p < 0.05). Similar improvements were noted in histologic responders from 100 mg or 80 mg resmetirom groups when separated-no improvements in placebo or nonresponders. Baseline F3 histologic responders had similar/more pronounced HRQL improvements.
Patients with MASH/NASH with fibrosis improvement or the resolution of MASH with resmetirom experienced clinically meaningful and statistically significant HRQL improvements.
肝脏靶向性甲状腺激素受体-β激动剂resmetirom已获批用于治疗代谢功能障碍相关脂肪性肝炎（MASH）。我们评估了接受resmetirom治疗的MASH患者的健康相关生活质量（HRQL）。
无肝硬化且有确诊/疑似纤维化的MASH/非酒精性脂肪性肝炎（NASH）患者参加了一项为期54个月的双盲随机安慰剂对照III期临床试验，在基线和第52周进行系列活检评估（MAESTRO-NASH，NCT03900429）。使用非酒精性脂肪性肝病慢性肝病问卷（CLDQ-NAFLD）和肝病生活质量（LDQOL）评估HRQL。比较52周后各治疗组（resmetirom 80mg、resmetirom 100mg或安慰剂）的基线HRQL评分变化以及组织学反应（纤维化改善且非酒精性脂肪性肝病活动评分未恶化或MASH/NASH缓解且纤维化未恶化）。纳入966例意向性治疗患者：323例接受resmetirom 100mg，322例接受resmetirom 80mg，321例接受安慰剂。在第24周和第52周时，接受80mg或100mg resmetirom治疗的患者在CLDQ-NAFLD担忧领域的HRQL有所改善（均值从+0.21提高到+0.24，p<0.05）。在第52周时，接受resmetirom（100mg和80mg合并）治疗后达到组织学终点的受试者在CLDQ-NAFLD担忧领域的HRQL提高了0.46（41%达到最小临床重要差异[MCID]），在LDQOL领域：角色情绪提高3.0（28%达到MCID），健康困扰提高8.1（38%达到MCID），耻辱感提高3.5（39%达到MCID），LDQOL总分提高2.2（35%达到MCID）（均p<0.05）。100mg或80mg resmetirom组的组织学应答者分别有类似的改善，安慰剂组或无应答者无改善。基线F3组织学应答者的HRQL改善相似/更明显。
接受resmetirom治疗后纤维化改善或MASH缓解的MASH/NASH患者在HRQL方面有临床意义且具有统计学显著性的改善。
