Muñoz-Espinosa Linda E, Torre Aldo, Cisneros Laura, Montalvo Iaarah, Malé René, Mejía Scherezada, Aguilar Juan Ramón, Lizardi Javier, Zuñiga-Noriega Jaime, Eugenia Icaza María, Gasca-Díaz Frida, Hernández-Hernández Larissa, Cordero-Pérez Paula, Chi Luis, Torres Lilian, Rodríguez-Alvarez Fátima, Tapia Graciela, Poo Jorge Luis
Universidad Autónoma de Nuevo León, "Dr. José E. González" University Hospital, Monterrey, Mexico.
Instituto Nacional de Ciencias Médicas y Nutrición, Ciudad de México, Mexico.
Liver Int. 2025 Jun;45(6):e70131. doi: 10.1111/liv.70131.
Advanced liver fibrosis (ALF) predicts an adverse prognosis in chronic liver disease. In addition to etiological treatment, a new approach to stop or reverse residual fibrosis is desirable.
To assess the efficacy and safety of prolonged-release pirfenidone (PR-PFD) versus placebo in compensated cirrhosis.
180 patients with ALF (F4) were randomly assigned to: placebo, 1200 mg/d, and 1800 mg/d PR-PFD, plus standardised care, for 24mo. Frequency of lab tests: (3mo), liver stiffness measurement (LSM), FibroTest, ultrasound (US) (6mo), and endoscopy (annually).
Fibrosis evolution estimated from LSM was significantly lower only in the 1200 compared to placebo and 1800 groups (24.2 ± 2.4 vs. 15.4 ± 2.4; 27.6 ± 2.4 vs. 24.6 ± 2.4; 24.4 ± 2.3 vs. 23.3 ± 2.3 kPa, respectively, p < 0.001), in intergroup analysis, meeting the primary endpoint. Fibrotest was significantly lower only in the 1200 mg/d group, compared to baseline values (0.86 ± 0.02 vs. 0.83 ± 0.02 units, p < 0.001). Liver function test (LFT's) also improved as well as Model for End-Stage Liver Disease (MELD) score and quality of life (QoL). Decompensations occurred in 19 patients: 12 ascites (more frequent in placebo, p = 0.003), 5 variceal bleeding, 4 encephalopathies, 4 hepatocarcinomas. Adverse events were mainly mild gastrointestinal (n = 35, 48 and 46, p = 0.010) and cutaneous (n = 12, 15, and 22, p = 0.0001) in placebo, 1200 and 1800 mg/day, respectively.
PR-PFD at a dose of 1200 mg significantly decreased non-invasive liver fibrosis markers at 24 months and induced improvement in LFT's, MELD, and QoL in compensated cirrhosis, without safety concerns.
ClinicalTrials.gov identifier: NCT01046474.
晚期肝纤维化（ALF）预示着慢性肝病的不良预后。除了病因治疗外，需要一种新的方法来阻止或逆转残余纤维化。
评估缓释吡非尼酮（PR-PFD）与安慰剂相比在代偿期肝硬化中的疗效和安全性。
180例ALF（F4）患者被随机分为：安慰剂组、1200mg/d组和1800mg/d PR-PFD组，均接受标准化护理，为期24个月。实验室检查频率：（每3个月一次），肝脏硬度测量（LSM）、FibroTest、超声（US）（每6个月一次）和内镜检查（每年一次）。
在组间分析中，从LSM估计的纤维化进展仅在1200mg/d组显著低于安慰剂组和1800mg/d组（分别为24.2±2.4 vs. 15.4±2.4；27.6±2.4 vs. 24.6±2.4；24.4±2.3 vs. 23.3±2.3kPa，p<0.001），达到主要终点。与基线值相比，仅1200mg/d组的FibroTest显著降低（0.86±0.02 vs. 0.83±0.02单位，p<0.001）。肝功能检查（LFT's）以及终末期肝病模型（MELD）评分和生活质量（QoL）也有所改善。19例患者发生失代偿：12例腹水（安慰剂组更常见，p = 0.003），5例静脉曲张出血，4例肝性脑病，4例肝癌。不良事件主要为轻度胃肠道事件（分别为35例、48例和46例，p = 0.010）和皮肤事件（分别为12例、15例和22例，p = 0.0001），分别发生在安慰剂组、1200mg/d组和1800mg/d组。
1200mg剂量的PR-PFD在24个月时显著降低了非侵入性肝纤维化标志物，并使代偿期肝硬化患者的LFT's、MELD和QoL得到改善，且无安全问题。
ClinicalTrials.gov标识符：NCT01046474。
