Linda E. Muñoz-Espinosa, Aldo Torre, Laura Cisneros, Iaarah Montalvo, René Malé, Scherezada Mejía, Juan Ramón Aguilar, Javier Lizardi, Jaime Zuñiga-Noriega, María Eugenia Icaza, Frida Gasca-Díaz, Larissa Hernández-Hernández, Paula Cordero-Pérez, Luis Chi, Lilian Torres, Fátima Rodríguez-Alvarez, Graciela Tapia, Jorge Luis Poo
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In addition to etiological treatment, a new approach to stop or reverse residual fibrosis is desirable.</p>\n </section>\n \n <section>\n \n <h3> Objective</h3>\n \n <p>To assess the efficacy and safety of prolonged-release pirfenidone (PR-PFD) versus placebo in compensated cirrhosis.</p>\n </section>\n \n <section>\n \n <h3> Methods</h3>\n \n <p>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).</p>\n </section>\n \n <section>\n \n <h3> Results</h3>\n \n <p>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, <i>p</i> < 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, <i>p</i> < 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, <i>p</i> = 0.003), 5 variceal bleeding, 4 encephalopathies, 4 hepatocarcinomas. 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引用次数: 0
摘要
背景：晚期肝纤维化（ALF）预示着慢性肝病的不良预后。除了病原学治疗，一种新的方法来停止或逆转残余纤维化是可取的。目的评价缓释吡非尼酮（PR-PFD）与安慰剂治疗代偿性肝硬化的疗效和安全性。方法将180例ALF （F4）患者随机分为：安慰剂、1200mg /d和1800mg /d PR-PFD组，外加标准化治疗，疗程24个月。实验室检查频率：（3个月），肝硬度测量（LSM），纤维试验，超声（US）（6个月），内窥镜检查（每年）。结果与安慰剂组和1800组相比，LSM估计的纤维化进展仅在1200组中显着降低(24.2±2.4 vs 15.4±2.4；27.6±2.4 vs. 24.6±2.4；分别为24.4±2.3和23.3±2.3 kPa, p < 0.001)，组间分析，满足主要终点。与基线值相比，仅在1200 mg/d组中，Fibrotest显著降低（0.86±0.02比0.83±0.02单位，p < 0.001）。肝功能测试（LFT's）、终末期肝病模型（MELD）评分和生活质量（QoL）也有所改善。19例患者出现代偿失代偿：12例腹水（安慰剂组更常见，p = 0.003）， 5例静脉曲张出血，4例脑病，4例肝癌。安慰剂组、1200和1800 mg/天组的不良事件主要为轻度胃肠道（n = 35、48和46，p = 0.010）和皮肤（n = 12、15和22，p = 0.0001）。结论1200mg PR-PFD可显著降低24个月时无创肝纤维化指标，改善代偿性肝硬化患者的LFT、MELD和QoL，无安全性问题。试验注册ClinicalTrials.gov标识符：NCT01046474
Noninvasive Evaluation of Prolonged-Release Pirfenidone in Compensated Liver Cirrhosis. ODISEA Study, a Randomised Trial
Background
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.
Objective
To assess the efficacy and safety of prolonged-release pirfenidone (PR-PFD) versus placebo in compensated cirrhosis.
Methods
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).
Results
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.
Conclusion
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.
期刊介绍：
Liver International promotes all aspects of the science of hepatology from basic research to applied clinical studies. Providing an international forum for the publication of high-quality original research in hepatology, it is an essential resource for everyone working on normal and abnormal structure and function in the liver and its constituent cells, including clinicians and basic scientists involved in the multi-disciplinary field of hepatology. The journal welcomes articles from all fields of hepatology, which may be published as original articles, brief definitive reports, reviews, mini-reviews, images in hepatology and letters to the Editor.
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