Corporal Michael J. Crescenz VA Medical Center, Philadelphia, Pennsylvania; Division of Gastroenterology and Hepatology, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania.
Corporal Michael J. Crescenz VA Medical Center, Philadelphia, Pennsylvania; Division of Gastroenterology and Hepatology, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania.
Gastroenterology. 2019 May;156(6):1693-1706.e12. doi: 10.1053/j.gastro.2019.01.026. Epub 2019 Jan 18.
BACKGROUND & AIMS: Concerns related to hepatotoxicity frequently lead to discontinuation or non-initiation of 3-hydroxy-3-methylglutaryl-coenzyme A reductase therapy in patients with cirrhosis despite data supporting statin use. We investigated the independent effects of hyperlipidemia and statin exposure on mortality, hepatic decompensation, and hepatocellular carcinoma development in a large national cohort of patients with cirrhosis.
We performed a retrospective cohort study of patients with newly diagnosed cirrhosis from January 1, 2008 through June 30, 2016 in the Veterans Health Administration. Subjects were divided into 2 cohorts: 21,921 patients with prior statin exposure (existing users) and 51,023 statin-naïve individuals, of whom 8794 subsequently initiated statin therapy (new initiators) and 44,269 did not (non-initiators). Multivariable Cox proportional hazard models with inverse probability weighting were constructed to assess the effects of time-updating lipid profiles and cumulative exposure to statins on survival and hepatic decompensation. Statin-naïve new initiators were propensity matched with non-initiators to simulate a randomized controlled trial of statin use in cirrhosis.
In statin-naïve subjects, every 10-mg/dL increase in baseline total cholesterol was associated with a 3.6% decrease in mortality. In existing users, each year of continued statin exposure was associated with a hazard ratio of 0.920 (95% confidence interval 0.0.897-0.943) for mortality. After risk-set matching, each year of statin exposure among new initiators was associated with a hazard ratio of 0.913 (95% confidence interval 0.890-0.937) for mortality.
In a retrospective cohort study of veterans with a new diagnosis of cirrhosis, we associated hypercholesterolemia with well-preserved hepatic function and decreased mortality. Nonetheless, each cumulative year of statin exposure was associated with an independent 8.0%-8.7% decrease of mortality of patients with cirrhosis of Child-Turcotte-Pugh classes A and B.
尽管有数据支持他汀类药物的使用，但与肝毒性相关的担忧常常导致肝硬化患者停止或不开始使用 3-羟基-3-甲基戊二酰辅酶 A 还原酶治疗。我们在一个大型的全国肝硬化患者队列中，研究了高脂血症和他汀类药物暴露对死亡率、肝失代偿和肝细胞癌发展的独立影响。
我们对 2008 年 1 月 1 日至 2016 年 6 月 30 日期间在退伍军人健康管理局新诊断为肝硬化的患者进行了回顾性队列研究。受试者分为两组：21921 例有他汀类药物暴露史的患者（现有使用者）和 51023 例他汀类药物初治患者，其中 8794 例随后开始他汀类药物治疗（新使用者），44269 例未开始（未使用者）。采用逆概率加权的多变量 Cox 比例风险模型来评估脂质谱时间更新和他汀类药物累积暴露对生存和肝失代偿的影响。他汀类药物初治的新使用者与未使用者进行倾向匹配，以模拟肝硬化患者使用他汀类药物的随机对照试验。
在他汀类药物初治患者中，基线总胆固醇每增加 10mg/dL，死亡率降低 3.6%。在现有使用者中，继续使用他汀类药物的每一年与死亡率的风险比为 0.920（95%置信区间 0.897-0.943）。经过风险集匹配后，新使用者中每年使用他汀类药物与死亡率的风险比为 0.913（95%置信区间 0.890-0.937）。
在一项退伍军人新诊断为肝硬化的回顾性队列研究中，我们发现高胆固醇血症与肝功能良好和死亡率降低有关。尽管如此，每个累积年的他汀类药物暴露与 A 和 B 级 Child-Turcotte-Pugh 肝硬化患者的死亡率独立降低 8.0%-8.7%相关。
