Statin use and non-alcoholic steatohepatitis in at risk individuals
Statin use and non-alcoholic steatohepatitis in at risk individuals
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DOI：
10.1016/j.jhep.2015.05.006
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发表时间：
2015-09-01
影响因子：
25.7
通讯作者：
Valenti, Luca
中科院分区：
文献类型：
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作者：
Dongiovanni, Paola;Petta, Salvatore;Valenti, Luca
背景和目标：过量的肝脏游离胆固醇有助于非酒精性脂肪性肝炎的发病机制，他汀类药物可减少胆固醇合成。本研究的目的是评估他汀类药物的使用是否与脂肪性hepatitis. Methods相关的组织学肝损伤有关：在一个多中心队列中评估了他汀类药物使用、遗传危险因素和肝损伤之间的关系，该队列包括1201名欧洲个体，他们因疑似非酒精性脂肪性hepatitis接受了肝活检。记录了107名受试者使用他汀类药物的情况，并且以剂量依赖性方式与预防脂肪变性、NASH和F2-F4期纤维化相关（所有受试者调整后p <0.05）。在100名接受治疗的患者中，招募方式、性别、IFG或2型糖尿病的存在、PNPLA 3 I148 M风险等位基因、TM6SF 2 E167 K变体、年龄和BMI 1：1匹配，他汀类药物使用仍然与防止脂肪变性相关（OR 0.09，95% C。I. 0.01 - 0.32; p = 0.004）、脂肪性肝炎（OR 0.25，95% C. I. 0.13 - 0.47; p <0.001）和纤维化分期F2-F4（OR 0.42，95%C. I. 0.20 - 0.8; p = 0.017）。结果在第二次分析中得到证实，其中个体在招募中心内匹配（所有p <0.05）。他汀类药物对脂肪性肝炎的保护作用在不携带I148M PNPLA3风险变体的受试者中更强（相互作用p = 0.02），因为他汀类药物与阴性患者的脂肪性肝炎呈负相关（p <0.001），但与I148M变体阳性患者无关（p = n.s.）。结论：他汀类药物的使用与非酒精性脂肪性肝炎风险个体的全谱肝损伤保护相关。然而，I148 M PNPLA3风险变体限制了这种有益效果。(C)2015年欧洲肝脏研究协会。Elsevier B.V.出版，保留所有权利。
Background & Aims: Excess hepatic free cholesterol contributes to the pathogenesis of non-alcoholic steatohepatitis, and statins reduce cholesterol synthesis. Aim of this study was to assess whether statin use is associated with histological liver damage related to steatohepatitis.Methods: The relationship between statin use, genetic risk factors, and liver damage was assessed in a multi-center cohort of 1201 European individuals, who underwent liver biopsy for suspected non-alcoholic steatohepatitis.Results: Statin use was recorded in 107 subjects, and was associated with protection from steatosis, NASH, and fibrosis stage F2-F4, in a dose-dependent manner (adjusted p < 0.05 for all). In 100 treated patients matched 1: 1 for modality of recruitment, gender, presence of IFG or type 2 diabetes, PNPLA3 I148M risk alleles, TM6SF2 E167K variant, age, and BMI, statin use remained associated with protection from steatosis (OR 0.09, 95% C. I. 0.01-0.32; p = 0.004), steatohepatitis (OR 0.25, 95% C. I. 0.13-0.47; p < 0.001), and fibrosis stage F2-F4 (OR 0.42, 95% C. I. 0.20-0.8; p = 0.017). Results were confirmed in a second analysis, where individuals were matched within recruitment center (p < 0.05 for all). The protective effect of statins on steatohepatitis was stronger in subjects not carrying the I148M PNPLA3 risk variant (p = 0.02 for interaction), as statins were negatively associated with steatohepatitis in patients negative (p < 0.001), but not in those positive for the I148M variant (p = n.s.).Conclusions: Statin use was associated with protection towards the full spectrum of liver damage in individuals at risk of non-alcoholic steatohepatitis. However, the I148M PNPLA3 risk variant limited this beneficial effect. (C) 2015 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.