Suzuki Ayako, Karachaliou Georgia Sofia, Perkins Amy M, Dorn Chad, Reeves Ruth M, Arnold Timothy, Bashir Mustafa R, Efird Jimmy T, Abdelmalek Manal F, Diehl Anna Mae
Gastroenterology, Duke University Medical Center, Durham, NC, USA.
Gastroenterology, Durham VA Medical Center, Durham, NC, USA.
EClinicalMedicine. 2025 Aug 20;87:103431. doi: 10.1016/j.eclinm.2025.103431. eCollection 2025 Sep.
The hepatoprotective effects of statins in chronic liver diseases are well-documented; however, variation by age, sex, and formulation remains unclear. The optimal regimen for cirrhosis prevention has yet to be defined. We aimed to address this knowledge gap.
In this retrospective cohort study using Veterans Affairs (VA) electronic health records, we defined a cohort of patients with chronic liver enzyme elevation primarily associated with metabolic dysfunction, between Jan 1, 2007, and Dec 31, 2009. Patients were followed-up for incident cirrhosis for a 10-year period until 2019. Time to cirrhosis was analysed using Cox proportional hazards models, with and without adjustment for demographics, relevant comorbidities, and co-medications. Hazard ratio (HR) estimates were used to compare event rates between groups. We also assessed potential effect modification by age and sex and evaluated differences across statin formulations.
In adjusted models, baseline statin use was significantly associated with a reduced risk of cirrhosis over 10 years (HR 0.74 [95% confidence interval 0.70-0.78], p < 0.0001). Cumulative statin dose, standardised by low-density lipoprotein (LDL)-lowering intensity as simvastatin-equivalent units, and duration were dose-dependently associated with cirrhosis risk reduction (p < 0.05). The protective effect of statin use, at baseline and during follow-up, demonstrated a significant effect modification with age (p ≤ 0.01), with greater protection in older individuals. No sex disparities were observed. Borderline to significant protection against cirrhosis was achieved with a daily dose of ≥6961 mg simvastatin-equivalent for at least 245 days per year among individuals aged ≥54 years. Those younger than 54 years required a higher dose (>15,561 mg annually) to achieve comparative protection. No significant differences in effectiveness were observed among different formulations.
Statins reduce cirrhosis risk in a dose- and age-dependent manner. A daily dose equivalent to ≥20 mg simvastatin (or >40 mg for <54 years) appears effective, regardless of formulation. Independent validation in a cohort with a higher proportion of women is warranted.
The Department of Defence, Translational Team Science Award.
他汀类药物在慢性肝病中的肝脏保护作用已有充分记录；然而，其在年龄、性别和剂型方面的差异仍不清楚。预防肝硬化的最佳治疗方案尚未确定。我们旨在填补这一知识空白。
在这项使用退伍军人事务部（VA）电子健康记录的回顾性队列研究中，我们确定了一组在2007年1月1日至2009年12月31日期间主要因代谢功能障碍导致慢性肝酶升高的患者。对患者进行了为期10年的随访，直至2019年，观察肝硬化的发生情况。使用Cox比例风险模型分析肝硬化发生时间，模型调整了人口统计学、相关合并症和联合用药情况。风险比（HR）估计值用于比较组间事件发生率。我们还评估了年龄和性别的潜在效应修饰作用，并评估了不同他汀类药物剂型之间的差异。
在调整后的模型中，基线时使用他汀类药物与10年内肝硬化风险降低显著相关（HR 0.74 [95%置信区间0.70 - 0.78]，p < 0.0001）。以降低低密度脂蛋白（LDL）强度标准化为辛伐他汀等效单位的累积他汀剂量和用药时长与肝硬化风险降低呈剂量依赖性相关（p < 0.05）。基线和随访期间使用他汀类药物的保护作用在年龄方面显示出显著的效应修饰（p ≤ 0.01），对老年人的保护作用更大。未观察到性别差异。在年龄≥54岁的个体中，每天剂量≥6961毫克辛伐他汀等效单位且每年至少245天可实现对肝硬化接近显著的保护作用。54岁以下的个体需要更高剂量（每年>15,561毫克）才能实现类似的保护作用。不同剂型之间在有效性方面未观察到显著差异。
他汀类药物以剂量和年龄依赖性方式降低肝硬化风险。无论剂型如何，相当于每天≥20毫克辛伐他汀（54岁以下为>40毫克）的剂量似乎有效。有必要在女性比例更高的队列中进行独立验证。
美国国防部转化团队科学奖
Zotero 插件