Sección de Hepatología, Hospital de Gastroenterología Dr. Carlos Bonorino Udaondo, Facultad de Medicina, Universidad de Buenos Aires, Av. Caseros 2061 (1264), Ciudad Autónoma de Buenos Aires, Argentina.
Instituto de Investigaciones en Salud Pública, Facultad de Odontología, Universidad de Buenos Aires, Marcelo T. Alvear 2142 (1122), Ciudad Autónoma de Buenos Aires, Argentina.
Dig Dis Sci. 2021 Sep;66(9):3199-3208. doi: 10.1007/s10620-020-06630-7. Epub 2020 Oct 9.
The high mortality rate of decompensated cirrhosis underlines the need for new treatments. Experimental models of cirrhosis and its reported relationship with atherosclerotic cardiovascular disease have provided data supporting the rational use of statins in these patients. However, little is known about the safety of statins in this setting.
We evaluate the safety of chronic simvastatin treatment in patients with decompensated cirrhosis.
We conducted a prospective, open, uncontrolled, phase 2a trial in 30 patients with Child-Pugh class A (n = 6), B (n = 22), and C (n = 2) decompensated cirrhosis. The patients received standard treatment throughout the trial plus simvastatin 20 mg/day for 2 weeks and thereafter simvastatin 40 mg/day up to 1 year.
Sixteen out of 30 patients (53.3%) showed adverse events, including gastrointestinal toxicity (36.7%), muscle injury (MI) (36.7%), and headache (13.3%). No liver injury was registered. Due to MI alone, simvastatin dosage was reduced in 23.4% of cases and transiently interrupted in 13.3%. Once these adverse events were overcome, simvastatin was resumed until the end of the trial. MI was associated with baseline MELD score > 12 (p = 0.035) and with baseline Child-Pugh class C. No MI was associated with final Child-Pugh score ≤ 6 (p = 0.030) or final Child-Pugh class A (p = 0.020).
Chronic treatment with simvastatin 40 mg/day in patients with decompensated cirrhosis was associated with several adverse events, being MI the only clinically significant one, which appears to be related to the simvastatin dosage and the degree of cirrhosis severity. Noticeably, no liver injury was recorded.
代偿期肝硬化的高死亡率凸显了对新疗法的需求。肝硬化的实验模型及其与动脉粥样硬化性心血管疾病的关系报告提供了支持在这些患者中合理使用他汀类药物的数据。然而，关于他汀类药物在这种情况下的安全性知之甚少。
我们评估慢性辛伐他汀治疗失代偿期肝硬化患者的安全性。
我们进行了一项前瞻性、开放、非对照、2a 期临床试验，纳入了 30 名 Child-Pugh 分级为 A（n=6）、B（n=22）和 C（n=2）的失代偿期肝硬化患者。所有患者在整个试验期间接受标准治疗，同时加用辛伐他汀 20mg/天，持续 2 周，然后剂量增至 40mg/天，持续 1 年。
30 名患者中有 16 名（53.3%）出现不良事件，包括胃肠道毒性（36.7%）、肌肉损伤（MI）（36.7%）和头痛（13.3%）。未发生肝损伤。由于 MI 单独发生，23.4%的病例减少了辛伐他汀剂量，13.3%的病例暂时中断了治疗。一旦这些不良事件得到解决，就恢复辛伐他汀治疗，直至试验结束。MI 与基线 MELD 评分>12（p=0.035）和基线 Child-Pugh 分级 C 相关。无 MI 与最终 Child-Pugh 评分≤6（p=0.030）或最终 Child-Pugh 分级 A（p=0.020）相关。
失代偿期肝硬化患者每天服用辛伐他汀 40mg 的慢性治疗与多种不良事件相关，其中 MI 是唯一具有临床意义的不良事件，其似乎与辛伐他汀剂量和肝硬化严重程度有关。值得注意的是，未记录到肝损伤。
