Backgrounds & Aims

There is a need to identify therapies that prevent the development of acute-on-chronic liver failure (ACLF) in patients with cirrhosis. This study sought to evaluate the association between statin exposure and the risk of developing ACLF in a large national cohort of patients with cirrhosis.

Methods

We performed a retrospective cohort study of patients diagnosed with cirrhosis within the Veterans Health Administration from 2008 and 2018. Patients were stratified into 3 groups based on statin exposure (statin naïve, existing statin user, and new statin initiator). Cox proportional hazards regression models with inverse probability treatment weighting and marginal structural models were utilized to comprehensively address potential confounding in estimating the association between time-updated statin exposure and first occurrence of high-grade ACLF.

Results

The cohort included 84,963 patients, of whom 26.9% were on a statin at baseline. A total of 8,558 (10.1%) patients with cirrhosis were hospitalized with high-grade ACLF over a median follow-up time of 51.6 months (IQR 27.5–81.4). Time-updated statin use was associated with a significant reduction in the hazard of developing ACLF (hazard ratio [HR] 0.62, 95% CI 0.59-0.65, p <0.001). Increasing doses of statin were associated with progressively reduced hazard of developing ACLF (HR 0.75, 95% CI 0.66-0.86, p <0.001 for <20 mg vs. 0 mg of time-updated statin exposure, in simvastatin equivalents; HR 0.61, 95%, CI 0.58-0.64, p <0.001 for >20 mg vs. 0 mg statin exposure). Furthermore, every additional 5 months of statin exposure was associated with a 9% reduced hazard of high-grade ACLF (HR 0.91, 95% CI 0.90-0.92, p <0.001).

Conclusions

In this large, retrospective, cohort study in patients with cirrhosis, statin use was significantly associated with reduced development of high-grade ACLF.

Lay summary

Statin therapy has been shown to have numerous beneficial effects in patients with chronic liver disease. This study demonstrated a strong association between statin therapy and a reduced risk of acute-on-chronic liver failure development in patients with cirrhosis. The results of this study support the promising role that statins may play in future prevention of acute-on-chronic liver failure in patients with cirrhosis.

中文翻译：

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在退伍军人事务队列中，他汀类药物暴露与慢加急性肝衰竭的发展减少有关

背景与目标

需要确定预防肝硬化患者发生慢性肝衰竭 (ACLF) 的治疗方法。本研究试图在全国大型肝硬化患者队列中评估他汀类药物暴露与发生 ACLF 风险之间的关联。

方法

我们对 2008 年和 2018 年退伍军人健康管理局诊断为肝硬化的患者进行了一项回顾性队列研究。根据他汀类药物暴露情况将患者分为 3 组（他汀类药物初治者、现有他汀类药物使用者和新他汀类药物启动者）。使用具有逆概率治疗加权和边际结构模型的 Cox 比例风险回归模型来全面解决估计时间更新他汀类药物暴露与首次发生高级 ACLF 之间关联的潜在混杂问题。

结果

该队列包括 84,963 名患者，其中 26.9% 在基线时服用他汀类药物。共有 8,558 名 (10.1%) 肝硬化患者因高级别 ACLF 住院，中位随访时间为 51.6 个月 (IQR 27.5–81.4)。及时更新他汀类药物的使用与发生 ACLF 的风险显着降低相关（风险比 [HR] 0.62，95% CI 0.59-0.65，p < 0.001）。增加他汀类药物剂量与逐渐降低发生 ACLF 的风险相关（HR 0.75, 95% CI 0.66-0.86, p < 0.001 for <20 mg vs. 0 mg time-updated statin exposure, in simvastatin equivalents; HR 0.61, 95 %，CI 0.58-0.64，p < 0.001 对于 >20 mg与0 毫克他汀类药物暴露）。此外，他汀类药物暴露每增加 5 个月，重度 ACLF 的风险就会降低 9%（HR 0.91，95% CI 0.90-0.92，p < 0.001）。

结论

在这项针对肝硬化患者的大型回顾性队列研究中，他汀类药物的使用与减少高级别 ACLF 的发生显着相关。

外行总结

他汀类药物治疗已被证明对慢性肝病患者有许多有益作用。这项研究表明，他汀类药物治疗与肝硬化患者发生慢性肝衰竭急性发作的风险降低之间存在很强的相关性。这项研究的结果支持他汀类药物在未来预防肝硬化患者慢性肝功能衰竭方面可能发挥的重要作用。