治疗慢性肝病的新药:辛伐他汀*

doi:10.3969/j.issn.1672-5069.2021.04.038

摘要/Abstract

摘要： 目的辛伐他汀除了具有降脂特性外,还具有抗氧化、抗增殖和抗炎等多种功能,同时能改善内皮细胞功能和刺激新生血管生成,临床上很少出现明显的急性肝损伤副作用,为慢性肝病的治疗提供了一个新的选择。本文简要介绍了辛伐他汀治疗慢性肝病的基础和临床研究现状。

关键词: 慢性肝病, 辛伐他汀, 治疗

Abstract: Objective Besides its lipid-lowering function, the simvastatin also exhibits multiple pleiotropic effects, such as antioxidative, antiproliferative and antiinflammatory properties, as well as the capacity to improve endothelial function and to stimulate neoangiogenesis. It rarely lead to apparent clinical acute liver injury, and might be a new choice for the treatment of patients with chronic liver diseases. In this article, we briefly introduce the basic and clinical researches of simvastatin in the treatment of patients with chronic liver diseases.

Key words: Chronic liver diseases, Simvastatin, Therapy

毕再鸿, 韩白乙拉, 王炳元. 治疗慢性肝病的新药:辛伐他汀^*[J]. 实用肝脏病杂志, 2021, 24(4): 603-606.

Bi Zaihong, Hanbai Yila, Wang Bingyuan. Simvastatin: a newface for treatment of patients with chronic liver disease[J]. Journal of Practical Hepatology, 2021, 24(4): 603-606.

参考文献

[1] Pose E, Trebicka J, Mookerjee RP, et al. Statins: Old drugs as new therapy for liver diseases? J Hepatol,2019,70(1):194-202.
[2] Wen J, Wu Y, Wei W, et al. Protective effects of recombinant human cytoglobin against chronic alcohol-induced liver disease in vivo and in vitro.Sci Rep,2017,7:41647.
[3] Guixé-Muntet S, de Mesquita FC, Vila S, et al. Cross-talk between autophagy and KLF2 determines endothelial cell phenotype and microvascular function in acute liver injury. J Hepatol, 2017,66(1):86-94.
[4] Meireles CZ, Pasarin M, Lozano JJ, et al. Simvastatin attenuates liver injury in rodents with biliary cirrhosis submitted to hemorrhage/resuscitation.Shock,2017,47(3):370-377.
[5] Zafra C, Abraldes JG, Turnes J, et al. Simvastatin enhances hepatic nitric oxide production and decreases the hepatic vascular tone in patients with cirrhosis. Gastroenterology,2004,126(3):749-755.
[6] Pollo-Flores P, Soldan M, Santos UC, et al. Three months of simvastatin therapy vs. placebo for severe portal hypertension in cirrhosis: A randomized controlled trial. Dig Liver Dis,2015,47(11):957-963.
[7] Abraldes JG, Albillos A, Bañares R, et al. Simvastatin lowers portal pressure in patients with cirrhosis and portal hypertension: a randomized controlled trial. Gastroenterology, 2009,136(5):1651-1658.
[8] Bishnu S, Ahammed SM, Sarkar A, et al. Effects of atorvastatin on portal hemodynamics and clinical outcomes in patients with cirrhosis with portal hypertension. Eur J Gastroenterol Hepatol, 2018,30(1):54-59.
[9] Jiang H. Simvastatin protects high glucose-induced H9c2 cells from injury by inducing autophagy. Pharm Biol,2020,58(1):1077-1084.
[10] Li H, Rabearivony A, Zhang W, et al. Chronopharmacology of simvastatin on hyperlipidaemia in high-fat diet-fed obese mice. J Cell Mol Med,2020,24(18):11024-11029.
[11] Hide D, Warren A, Fernández-Iglesias A, et al. Ischemia/reperfusion injury in the aged liver: The importance of the sinusoidal endothelium in developing therapeutic strategies for the elderly. J Gerontol A Biol Sci Med Sci,2020,75(2):268-277.
[12] Bosch J, Gracia-Sancho J, Abraldes JG. Cirrhosis as new indication for statins.Gut,2020,69(5):953-962.
[13] Liu Z, Lai CH, Zhang X, et al. Simvastatin ameliorates total liver ischemia/reperfusion injury via KLF2-mediated mechanism in rats. Clin Res Hepatol Gastroenterol,2019,43(2):171-178.
[14] Tripathi DM, Vilaseca M, Lafoz E, et al. Simvastatin prevents progression of acute on chronic liver failure in rats with cirrhosis and portal hypertension.Gastroenterology,2018,155(5):1564-1577.
[15] La Mura V, Pasarín M, Meireles CZ, et al. Effects of simvastatin administration on rodents with lipopolysaccharide-induced liver microvascular dysfunction.Hepatology,2013,57(3):1172-1181.
[16] Baiges A, Hernández-Gea V, Bosch J. Pharmacologic prevention of variceal bleeding and rebleeding.Hepatol Int,2018,12(Suppl 1):68-80.
[17] Stolf AM, Lívero Fdos R, Dreifuss AA, et al. Effects of statins on liver cell function and inflammation in septic rats.J Surg Res, 2012,178(2):888-897.
[18] Chang FM, Wang YP, Lang HC, et al. Statins decrease the risk of decompensation in hepatitis B virus- and hepatitis C virus-related cirrhosis: A population-based study.Hepatology, 2017,66(3):896-907.
[19] Abraldes JG, Albillos A, Bañares R, et al. Simvastatin lowers portal pressure in patients with cirrhosis and portal hypertension: a randomized controlled trial.Gastroenterology, 2009,136(5):1651-1658.
[20] Elwan N, Salah R, Hamisa M, et al. Evaluation of portal pressure by Doppler ultrasound in patients with cirrhosis before and after simvastatin administration - a randomized controlled trial. F1000Res, 2018,7:256.
[21] Abraldes JG, Villanueva C, Aracil C, et al. BLEPS Study Group. Addition of simvastatin to standard therapy for the prevention of variceal rebleeding does not reduce rebleeding but increases survival in patients with cirrhosis. Gastroenterology, 2016,150(5):1160-1170.
[22] Feng J, Dai W, Mao Y, et al. Simvastatin re-sensitizes hepatocellular carcinoma cells to sorafenib by inhibiting HIF-1α/PPAR-γ/PKM2-mediated glycolysis.J Exp Clin Cancer Res, 2020,39(1):24.
[23] 张宁, 赵彩彦. 他汀类药物对肝细胞癌的作用与机制研究进展.实用肝脏病杂志,2015,18 (3): 329-332.
[24] Dongiovanni P, Petta S, Mannisto V, et al. Statin use and non-alcoholic steatohepatitis in at risk individuals.J Hepatol,2015,63(3):705-712.
[25] Nascimbeni F, Aron-Wisnewsky J, Pais R, et al. LIDO study Group. Statins, antidiabetic medications and liver histology in patients with diabetes with non-alcoholic fatty liver disease.BMJ Open Gastroenterol,2016,3(1):e000075.
[26] 袁乐媛,韩惠芳,王炳元,等.酒精性肝病与血脂代谢相关性分析.胃肠病学和肝病学杂志,2015,24(8):973-976.
[27] 钟碧慧. 降脂药物在NAFLD患者中的合理应用. 实用肝脏病杂志, 2016,19(2):143-146.
[28] Atef MM, Hafez YM, Alshenawy HA, et al. Ameliorative effects of autophagy inducer, simvastatin on alcohol-induced liver disease in a rat model.J Cell Biochem,2018,234:136-143.
[29] Zhao G, Yu YM, Kaneki M, et al. Simvastatin protects hepatocytes from apoptosis by suppressing the TNF-α/caspase-3 signaling pathway in mice with burn injury.Ann Surg,2013,257(6):1129-1136.
[30] Carloni S, Balduini W. Simvastatin preconditioning confers neuroprotection against hypoxia-ischemia induced brain damage in neonatal rats via autophagy and silent information regulator 1 (SIRT1) activation.Exp Neurol,2020,324:113117.
[31] U.S. Food and Drug Administration (FDA). FDA drug safety communication: important safety label changes to cholesterol-lowering statin drugs. Rockville, MD, 2012. Available: http://www.fda.gov/drugs/drugsafety/ucm293101.htm.
[32] Chalasani N, Aljadhey H, Kesterson J, et al. Patients with elevated liver enzymes are not at higher risk for statin hepatotoxicity. Gastroenterology,2004,126(5):1287-1292.
[33] Muñoz AE, Pollarsky F, Marino M, et al. Safety of chronic simvastatin treatment in patients with decompensated cirrhosis: Many adverse events but no liver injury. Dig Dis Sci,2020,84:2345-2349.
[34] Pose, E, Napoleone, L, Amin, A, et al. (2020). Safety of two different doses of simvastatin plus rifaximin in decompensated cirrhosis (LIVERHOPE-SAFETY): a randomised, double-blind, placebo-controlled, phase 2 trial.Lancet Gastroenterol Hepatol,2019,5(1), 31-41.
[35] Dickerman BA, García-Albéniz X, Logan RW, et al. Avoidable flaws in observational analyses: an application to statins and cancer. Nat Med, 2019,25(10):1601-1606.

治疗慢性肝病的新药:辛伐他汀^*

Simvastatin: a newface for treatment of patients with chronic liver disease

PDF (PC)

可视化

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 15

编辑推荐

Metrics

本文评价

[1]	张佳, 晋明渊, 杜艳云, 胡秀娟, 王烈姣. NAFLD合并Hp感染患者清除治疗前后血清细胞因子水平变化^*[J]. 实用肝脏病杂志, 2021, 24(4): 500-503.
[2]	刘永昌, 赵殿堂, 孙启峰, 张启文. 吲哚菁绿荧光导航和三维可视化腹腔镜精准手术治疗原发性肝癌患者应用研究^*[J]. 实用肝脏病杂志, 2021, 24(4): 561-564.
[3]	王雪梅, 张瑶, 杨学平, 王玥, 张记. 超声引导下经皮肝穿刺抽脓法和置管引流法治疗艾滋病并发肝脓肿患者临床效果分析[J]. 实用肝脏病杂志, 2021, 24(4): 573-576.
[4]	唐文涛, 黄会, 蔡婵娟. 平阳霉素联合超化碘油混悬液经动脉介入栓塞治疗肝血管瘤患者中远期疗效研究^*[J]. 实用肝脏病杂志, 2021, 24(4): 581-584.
[5]	史海军, 张日欣, 宁纯民. 规则性肝叶切除治疗复杂性肝内胆管结石患者疗效研究[J]. 实用肝脏病杂志, 2021, 24(4): 585-588.
[6]	付前广, 李倩, 冯小雪, 王勇, 邓如兵, 崔畅. 腹腔镜胆总管探查术联合腹腔镜胆囊切除术治疗胆囊结石合并胆总管结石患者临床疗效研究^*[J]. 实用肝脏病杂志, 2021, 24(4): 589-592.
[7]	安西全, 李燕, 孟根才次克. 替诺福韦联合索拉非尼治疗乙型肝炎相关中晚期原发性肝癌患者临床观察[J]. 实用肝脏病杂志, 2021, 24(4): 600-602.
[8]	袁平戈, 陈文雯. 非酒精性脂肪性肝炎新药研发临床思考[J]. 实用肝脏病杂志, 2021, 24(3): 305-307.
[9]	徐文婷, 张继红, 韦冬珏, 李巍. 替诺福韦补救治疗rtM204位点突变的慢性乙型肝炎患者效果研究[J]. 实用肝脏病杂志, 2021, 24(3): 335-338.
[10]	王雪, 瞿发林, 戚伟利, 钱薇. 慢性乙型肝炎患者外周血Treg/Th17比值平衡及其对替比夫定治疗效果的影响[J]. 实用肝脏病杂志, 2021, 24(3): 339-342.
[11]	陈熙, 王玮, 高健伟, 许乐. 合并非酒精性脂肪性肝病对恩替卡韦治疗慢性乙型肝炎患者抗病毒疗效的影响[J]. 实用肝脏病杂志, 2021, 24(3): 343-346.
[12]	裴旭东, 张晓虎, 褚桂克, 李延玲, 赵萍, 王立坤, 陈新菊. 消脂祛浊方治疗合并肥胖的痰湿型非酒精性单纯性脂肪肝患者临床效果初步研究[J]. 实用肝脏病杂志, 2021, 24(3): 355-358.
[13]	齐玫, 张瑞金, 田树萍, 于艳华. 平均血小板体积对自身免疫性肝炎患者治疗不应答的预测价值分析[J]. 实用肝脏病杂志, 2021, 24(3): 371-374.
[14]	王云强, 王丽萍, 黄冬梅, 王艳彬, 刘晓杰, 李明宇, 赵欣宇. 经颈静脉肝内门体静脉分流术治疗乙型肝炎肝硬化门脉高压症患者疗效和血流动力学变化分析[J]. 实用肝脏病杂志, 2021, 24(3): 399-402.
[15]	伍畅, 张远安, 彭春芬. 内镜下套扎术后应用卡维地洛治疗肝硬化并发食管胃底静脉曲张破裂出血患者疗效研究[J]. 实用肝脏病杂志, 2021, 24(3): 403-406.