Statin exposure is associated with reduced development of acute-on-chronic liver failure in a Veterans Affairs cohort.
Statin exposure is associated with reduced development of acute-on-chronic liver failure in a Veterans Affairs cohort.
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DOI：
10.1016/j.jhep.2021.12.034
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发表时间：
2022-05
影响因子：
25.7
通讯作者：
Kaplan, David E.
中科院分区：
文献类型：
--
作者：
Mahmud, Nadim;Chapin, Sara;Goldberg, David S.;Reddy, K. Rajender;Taddei, Tamar H.;Kaplan, David E.
关键词：
需要确定可以预防肝硬化患者发生慢加急性肝衰竭（ACLF）的疗法。本研究旨在评估全国大型肝硬化患者队列中他汀类药物暴露与发生 ACLF 风险之间的关联。我们对 2008 年至 2018 年退伍军人健康管理局内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三组（未使用他汀类药物、现有他汀类药物使用者和新的他汀类药物起始者）。利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的他汀类药物暴露与首次发生高级别 ACLF 之间的关联时的潜在混杂因素。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。中位随访时间为 51.6 个月 (IQR 27.5, 81.4)，共有 8,558 名肝硬化患者 (10.1%) 因高级别 ACLF 住院。随时间更新的他汀类药物使用与发生 ACLF 的风险显着降低相关（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（辛伐他汀当量，HR 0.75，95% CI 0.66-0.86，p<0.001，<20mg vs. 0mg 时间更新的他汀类药物暴露；HR 0.61, 95%，CI 0.58-0.64，p<0.001，>20mg vs. 0mg他汀类药物暴露）。此外，每增加 5 个月的他汀类药物暴露，高级 ACLF 的风险就会降低 9%（HR 0.91，95% CI 0.90-0.92，p<0.001）。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高级 ACLF 发展的减少显着相关。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，他汀类药物治疗与降低肝硬化患者发生慢加急性肝衰竭的风险之间存在密切关系。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加急性肝衰竭方面可能发挥的有希望的作用。
There is a need to identify therapies that may prevent 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. We performed a retrospective cohort study of patients diagnosed with cirrhosis within the Veterans Health Administration from 2008 and 2018. Patients were stratified into three 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. The cohort included 84,963 patients, of which 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 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 (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 <20mg vs. 0mg of time-updated statin exposure, in simvastatin equivalents; HR 0.61, 95%, CI 0.58-0.64, p<0.001 for >20mg vs. 0mg 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). In this large, retrospective cohort study in patients with cirrhosis, statin use was significantly associated with reduced development of high-grade ACLF. 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 for the development of acute-on-chronic liver failure 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.
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DOI：
10.1002/hep.31558
发表时间：
2021-01
期刊：
Hepatology (Baltimore, Md.)
影响因子：
--
作者：
Mahmud N;Fricker Z;Hubbard RA;Ioannou GN;Lewis JD;Taddei TH;Rothstein KD;Serper M;Goldberg DS;Kaplan DE
通讯作者：
Kaplan DE
2001-2013 年美国退伍军人肝硬化和肝细胞癌负担趋势（按肝脏疾病分类
影响因子：
29.4
作者：
Beste, Lauren A.;Leipertz, Steven L.;Ioannou, George N.
通讯作者：
Ioannou, George N.
影响因子：
25.7
作者：
Marrone, Giusi;Russo, Lucia;Gracia-Sancho, Jorge
通讯作者：
Gracia-Sancho, Jorge
DOI：
10.13063/2327-9214.1023
发表时间：
2013
期刊：
EGEMS (Washington, DC)
影响因子：
--
作者：
Davis LA;Mann A;Cannon GW;Mikuls TR;Reimold AM;Caplan L
通讯作者：
Caplan L
影响因子：
2
作者：
Austin, Peter C.
通讯作者：
Austin, Peter C.