西班牙巴塞罗那Clínic de Barcelona医院Pere Ginès团队研究了辛伐他汀和利福昔明治疗失代偿性肝硬化的疗效与安全性。该研究于2025年2月5日发表于《美国医学会杂志》。

目前尚无有效的治疗方法来预防肝硬化严重并发症的发展。辛伐他汀和利福昔明对肝硬化显示出有益作用。

为了探讨辛伐他汀联合利福昔明是否能改善失代偿性肝硬化患者的预后，2019年1月至2022年12月，研究组在14家欧洲医院对失代偿性肝硬化患者进行了双盲、安慰剂对照、3期试验。最后一次随访日期为2022年12月。患者被随机分配接受辛伐他汀20mg/d和利福昔明1200mg/d治疗（n=117），或相同外观的安慰剂（n=120），除标准治疗外，持续12个月，根据Child-Pugh B或C级分层。主要终点是与器官衰竭相关的肝硬化严重并发症的发生率，符合急性或慢性肝衰竭的标准。次要结局包括移植或死亡以及肝硬化并发症的复合终点（腹水、肝性脑病、静脉曲张出血、急性肾损伤和感染）。

在237名随机参与者中（Child-Pugh B级：n=194；Child-Pugh C级：n=43），72%为男性，平均年龄57岁。两组在急性至慢性肝衰竭的发展（治疗组和安慰剂组分别为21名[17.9%]和17名[14.2%]患者；风险比为1.23；95%置信区间为0.65-2.34；P = .52）；移植或死亡（治疗组和安慰剂组分别有22名[18.8%]和29名[24.2%]患者；风险比为0.75；95%置信区间为0.43-1.32；P = .32）；或肝硬化并发症的发生（治疗组和安慰剂组分别有50名[42.7%]和55名[45.8%]患者；风险比为0.93；95%置信区间为0.63-1.36；P = .70）方面没有差异。两组的不良事件发生率相似（426 vs 419；P=0.59），但治疗组3例（2.6%）出现横纹肌溶解症。

研究结果表明，在标准治疗中加入辛伐他汀和利福昔明并不能改善失代偿性肝硬化患者的预后。

附：英文原文

Title: Simvastatin and Rifaximin in Decompensated Cirrhosis: A Randomized Clinical Trial

Author: Elisa Pose, César Jiménez, Giacomo Zaccherini, Daniela Campion, Salvatore Piano, Frank Erhard Uschner, Koos de Wit, Olivier Roux, Kohilan Gananandan, Wim Laleman, Cristina Solé, Sonia Alonso, Berta Cuyàs, Xavier Ariza, Adrià Juanola, Ann T. Ma, Laura Napoleone, Jordi Gratacós-Ginès, Marta Tonon, Enrico Pompili, Jordi Sánchez-Delgado, Andrew S. Allegretti, Manuel Morales-Ruiz, Marta Carol, Martina Pérez-Guasch, Núria Fabrellas, Judit Pich, Claudia Martell, María Joyera, Gemma Domenech, José Ríos, Ferrán Torres, Miquel Serra-Burriel, Rubén Hernáez, Elsa Solà, Isabel Graupera, Hugh Watson, Germán Soriano, Rafael Baares, Rajeshwar P. Mookerjee, Claire Francoz, Ulrich Beuers, Jonel Trebicka, Paolo Angeli, Carlo Alessandria, Paolo Caraceni, Víctor M. Vargas, Juan G. Abraldes, Patrick S. Kamath, Pere Ginès, LIVERHOPE Consortium

Issue&Volume: 2025-02-05

Abstract:

Importance  There are no useful treatments to prevent the development of severe complications of liver cirrhosis. Simvastatin and rifaximin have shown beneficial effects in liver cirrhosis.

Objective  To assess whether simvastatin combined with rifaximin improves outcomes in patients with decompensated cirrhosis.

Design, Setting, and Participants  Double-blind, placebo-controlled, phase 3 trial conducted among patients with decompensated cirrhosis in 14 European hospitals between January 2019 and December 2022. The last date of follow-up was December 2022.

Interventions  Patients were randomly assigned to receive simvastatin, 20 mg/d, plus rifaximin, 1200 mg/d (n=117), or identical-appearing placebo (n=120) for 12 months in addition to standard therapy, stratified according to Child-Pugh class B or C.

Main Outcomes and Measures  The primary end point was incidence of severe complications of liver cirrhosis associated with organ failure meeting criteria for acute-on-chronic liver failure. Secondary outcomes included transplant or death and a composite end point of complications of cirrhosis (ascites, hepatic encephalopathy, variceal bleeding, acute kidney injury, and infection).

Results  Among the 237 participants randomized (Child-Pugh class B: n=194; Child-Pugh class C: n=43), 72% were male and the mean age was 57 years. There were no differences between the 2 groups in terms of development of acute-on-chronic liver failure (21 [17.9%] vs 17 [14.2%] patients in the treatment and placebo groups, respectively; hazard ratio, 1.23; 95% CI, 0.65-2.34; P=.52); transplant or death (22 [18.8%] vs 29 [24.2%] patients in the treatment and placebo groups, respectively; hazard ratio, 0.75; 95% CI, 0.43-1.32; P=.32); or development of complications of cirrhosis (50 [42.7%] vs 55 [45.8%] patients in the treatment and placebo groups, respectively; hazard ratio, 0.93; 95% CI, 0.63-1.36; P=.70). Incidence of adverse events was similar in both groups (426 vs 419; P=.59), but 3 patients in the treatment group (2.6%) developed rhabdomyolysis.

Conclusions and Relevance  The addition of simvastatin plus rifaximin to standard therapy does not improve outcomes in patients with decompensated liver cirrhosis.

DOI: 10.1001/jama.2024.27441

Source: https://jamanetwork.com/journals/jama/fullarticle/2829933