Application of lipid-regulating drugs in prevention and treatment of nonalcoholic fatty liver disease
-
摘要: 非酒精性脂肪性肝病(NAFLD)是指除外过量饮酒及其他明确肝损伤因素所致的,以弥漫性肝细胞大泡性脂肪变性为主要特征的临床病理综合征。其中,脂质代谢紊乱是NAFLD的重要特征,改善血脂异常乃是防治NAFLD的重要手段,而调脂药物在降低血脂的同时,也可能促使脂质更集中运输至肝脏进行代谢,造成肝脂蓄积而加重肝损伤。目前,国内对于调脂药物在NAFLD中的应用仍持谨慎态度甚至存在争议。如何合理应用调脂药物,已成为防治NAFLD的重要课题。简要综述了调脂药物在NAFLD中的应用进展,以期对调脂药物防治NAFLD提供一定参考。Abstract: Nonalcoholic fatty liver disease ( NAFLD) is a clinicopathological syndrome characterized by diffuse macrovesicular steatosis in hepatocytes and is caused by the factors except excessive drinking and other specific factors for liver injury. In particular, lipid metabolism disorder is a significant characteristic of NAFLD, and improvement of dyslipidemia is an important method for the prevention and treatment of NAFLD. Lipid-regulating drugs can not only reduce blood lipids, but also promote the transportation of lipids to the liver for metabolism, which may cause liver lipid accumulation and aggravate liver injury. At present, there are still controversies over the application of lipid-regulating drugs in the treatment of NAFLD in China. Rational use of lipid-regulating drugs has become an important topic in the prevention and treatment of NAFLD. This article summarizes the application of lipid-regulating drugs in NAFLD, in order to provide a reference for lipid-regulating drugs in the prevention and treatment of NAFLD.
-
Key words:
- nonalcoholic fatty liver disease /
- drug therapy /
- review
-
[1]CHALASANI N, YOUNOSSI Z, LAVINE JE, et al.The diagnosis and management of non-alcoholic fatty liver disease:practice guideline by the American Association for the Study of Liver Diseases, American College of Gastroenterology, and the American Gastroenterological Association[J].Hepatology, 2012, 55 (6) :2005-2023. [2]LOMONACO R, SUNNY NE, BRIL F, et al.Non-alcoholic fatty liver disease:current issues and novel treatment approaches[J].Drugs, 2013, 73 (1) :1-14. [3]LABRECQUE DR, ABBAS Z, ANANIA F, et al.World gastroenterology organisation global guidelines:nonalcoholic fatty liver disease and non-alcoholic steatohepatitis[J].J Clin Gastroenterol, 2014, 48 (6) :467-473. [4]BREA A, PUZO J.Non-alcoholic fatty liver disease and cardiovascular risk[J].Int J Cardiol, 2013, 167 (4) :1109-1117. [5]DONG S, LIU P, SUN MY.Role of“two-hit”in non-alcoholic fatty liver disease[J].J Clin Hepatol, 2012, 28 (7) :551-555. (in Chinese) 董姝, 刘平, 孙明瑜.非酒精性脂肪肝发病机制---“二次打击”学说研究进展[J].临床肝胆病杂志, 2012, 28 (7) :551-555. [6]TAKAKI A, KAWAI D, YAMAMOTO K.Multiple hits, including oxidative stress, as pathogenesis and treatment target in non-alcoholic steatohepatitis (NASH) [J].Int J Mol Sci, 2013, 14 (10) :20704-20728. [7]PAOLELLA G, MANDATO C, PIERRI L, et al.Gut-liver axis and probiotics:their role in non-alcoholic fatty liver disease[J].World J Gastroenterol, 2014, 20 (42) :15518-15531. [8]HE FP.Atherosclerosis in patients with nonalcoholic fatty liver disease[J].J Pract Hepatol, 2017, 20 (3) :263-266.何方平.非酒精性脂肪性肝病与动脉粥样硬化[J].实用肝脏病杂志, 2017, 20 (3) :263-266. [9]TARGHER G, DAY CP, BONORA E.Risk of cardiovascular disease in patients with non-alcoholic fatty liver disease[J].N Engl JMed, 2010, 363 (3) :1341-1350. [10]ATHYROS VG, TZIOMALOS K, KARAGIANNIS A.Statins for improving myocardial perfusion in patients with non-alcoholic fatty liver disease undergoing percutaneous coronary intervention[J].Am J Cardiol, 2016, 117 (2) :311-312. [11]TARANTINO G, SALDALAMACCHIA G, ARENA A, et al.Non-alcoholicfatty liver disease:further expression of the metabolicsyndrome[J].J Gastroenterol Hepatol, 2007, 22 (3) :293-303. [12]CHANG BX, ZOU ZS, LI BS, et al.2015 The Japanese Society of Gastroenterology of Evidence based clinical practice guidelines for nonalcoholic fatty live rdisease/nonal coholicsteatohepatitis[J].JClin Hepatol, 2015, 31 (7) :1027-1030. (in Chinese) 常彬霞, 邹正升, 李保森, 等.2015年日本胃肠病学会非酒精性脂肪性肝病/非酒精性脂肪性肝炎的循证医学临床治疗指南[J].临床肝胆病杂志, 2015, 31 (7) :1027-1030. [13]Asia-Pacific Working Group.The Asia-Pacific Working Party on non-alcoholic fatty liver disease guidelines 2017[J].J Gastroenterol Hepatol, 2017.[Epub ahead of print]. [14]Group of Fatty Liver and Alcoholic Liver Diseases, Society of Hepatology, Chinese Medical Association.Guidelines for Management of non-alcoholic fatty liver disease[J].J Clin Hepatol, 2010, 26 (2) :120-124. (in Chinese) 中华医学会肝脏病学分会脂肪肝和酒精性肝病学组.非酒精性脂肪性肝病诊疗指南[J].临床肝胆病杂志, 2010, 26 (2) :120-124. [15]UCHIYAMA H, TSUJIMOTO M, SHINMOTO T, et al.Uremic toxins enhance statin-induced cytotoxicity in differentiated human rhabdomyosarcoma cells[J].Toxins (Basel) , 2014, 6 (9) :2612-2625. [16]WILEY LK, MORETZ JD, DENNY JC, et al.Phenotyping adverse drug reactions:statin-related myotoxicity[J].AMIA Jt Summits Transl Sci Proc, 2015, 25 (5) :466-470. [17]BIRTCHER K.When compliance is an issue-how to enhance statin adherence and address adverse effect[J].Curr Atheroscler Rep, 2015, 17 (1) :471. [18]SCHULZE J, GLASS X.Statin hepatotoxicity and the dilemma of causality in rare hepatic adverse drug reactions[J].J Hepatol, 2012, 57 (3) :702-703. [19]ABDOLI N, HEIDARI R, AZARMI Y, et al.Mechanisms of the statins cytotoxicity in freshly isolated rat hepatocytes[J].J Biochem Mol Toxicol, 2013, 27 (6) :287-294. [20]TOLOSA L, CARMONA A, CASTELL JV, et al.High-content screening of drug-induced mitochondrial impairment in hepatic cells:effects of statins[J].Arch Toxicol, 2015, 89 (10) :1847-1860. [21]SZABO M, VERES Z, BATAI-KONCZOS A, et al.Statins alter the hepatobiliary transport of unconjugated and conjugated bilirubin sandwich-cultured rat hepatocytes[J].Toxicol In Vitro, 2014, 28 (6) :1136-1143. [22]GRAJALES-REYES GE, BAEZ-PAGAN CA, ZHU H, et al.Transgenic mouse model reveals an unsuspected role of the acetylcholine receptor in statin-induced neuromuscular adverse drug reactions[J].Pharmacogenomics J, 2013, 13 (4) :362-368. [23]DORMUTH CR, FILION KB, PATERSON JM, et al.Higher potency statins and the risks of new diabetes:multicentre, observational study of administrative databases[J].BMJ, 2014, 29 (348) :g3244. [24]SATTAR N, PREISS D, MURRAY HM, et al.Statins and risk of incident diabetes:a collaborative meta-analysis of randomised statin trials[J].Lancet, 2010, 375 (9716) :735-742. [25]PREISS D, SESHEHASAI SR, WELSH P, et al.Risk of incident diabetes with intensive-dose compared with moderate-dose statin therapy:a meta analysis[J].JAMA, 2011, 305 (24) :2556-2564. [26]CARTER AA, GOMES T, CAMACHO X, et al.Risk of incident diabetes among patients treated with statins:population based study[J].BMJ, 2013, 23 (346) :f2610. [27]RIDKER PM, PRADHAN A, MACFADYEN JG, et al.Cardiovascular benefits and diabetes risks of statin therapy in primary prevention:an analysis from the JUPITER trial[J].Lancet, 2012, 380 (9841) :565-571. [28]GOLDSTEIN LB, AMARENCO P, SZAREK M, et al.Hemorrhagic stroke in the Stroke Prevention by Aggressive Reduction in Cholesterol Levels study[J].Neurology, 2008, 70 (24 Pt 2) :2364-2370. [29]HYOGO H, YAMAGISHI S, MAEDA S, et al.Atorvastatin improves disease activity of nonalcoholic steatohepatitis partly through its tumour necrosis factor-α-lowering property[J].Dig Liver Dis, 2012, 44 (6) :492-496. [30]VUPPALANCHI R, CHALASANI N.Nonalcoholic fatty liver disease and nonalcoholic steatohepatitis:selected practical issues in their evaluation and management[J].Hepatology, 2009, 49 (2) :306-317. [31]LU YJ, CHEN ZY, YAN MX, et al.Effect of atorvastatin on adipokines in rats with nonalcoholic fatty liver disease[J].Chin J Clin Pharmacol Ther, 2015, 5 (20) :520-524. (in Chinese) 陆永娟, 陈芝芸, 严茂祥, 等.阿托伐他汀对非酒精性脂肪性肝病大鼠脂肪细胞因子的影响[J].中国临床药理学与治疗学, 2015, 20 (5) :520-524. [32]FRAULOB JC, SOUZA-MELLO V, AGUILA MB, et al.Beneficial effects of rosuvastatin on insulin resistance, adiposity, inflammatory markers an non-alcoholic fatty liver disease in mice fed on a high-fat diet[J].Clin Sci (Lond) , 2012, 123 (4) :259-270. [33]YOKOHAMA K, FUKUNISHI S, LI M, et al.Rosuvastatin as a potential preventive drug for the development of hepatocellular carcinoma associated with non-alcoholic fatty liver disease in mice[J].Int J Mol Med, 2016, 38 (5) :1499-1506. [34]ALKHATATBEH MJ, LINCZ LF, THORNE RF.Low simvastatin concentrations reduce oleic acid-induced steatosis in Hep G2 cells:an in vitro model of non-alcoholic fatty liver disease[J].Exp Ther Med, 2016, 11 (4) :1487-1492. [35]SAMY W, HASSANIAN MA.Paraoxonase-1 activity, malondialdehyde and glutathione peroxidase in non-alcoholic fatty liver disease and the effect of atorvastatin[J].Arab J Gastroenterol, 2011, 12 (2) :80-85. [36]FOSTER T, BUDOFF MJ, SAAB S, et al.Atorvastatin and antioxidantsfor the treatment of nonalcoholic fatty liver disease:the St Francis Heart Study randomized clinical trial[J].Am J Gastroenterol, 2011, 106 (1) :71-77. [37]European Association for the Study of the Liver (EASL) ;European Association for the Study of Diabetes (EASD) ;European Association for the Study of Obesity (EASO) .Clinical Practice Guidelines for themanagement of non-alcoholic fatty liver disease[J].J Hepatology, 2016, 64 (6) :1388-1402. [38]NELSON A, TORRES DM, MORGAN AE, et al.A pilot study using simvastatin in the treatment of nonalcoholic steatohepatitis:a randomized placebo-controlled trial[J].J Clin Gastroenterol, 2009, 43 (10) :990-994. [39]BJORNSSON ES.Hepatotoxicity of statins and other lipid-lowering agents[J].Liver Int, 2016, 37 (2) :173-178. [40]SHI JP, FAN JG.Advances in clinical research on nonalcoholic fatty liver disease in 2009[J].J Pract Hepatol, 2010, 13 (1) :1-3. (in Chinese) 施军平, 范建高.2009年非酒精性脂肪性肝病临床研究进展回顾[J].实用肝脏病杂志, 2010, 13 (1) :1-3. [41]CLHEN DE, ANANIA FA, CHALASANI N.An assessment of statin safety by hepatologists[J].Am J Cardiol, 2006, 97 (8) :77-81. [42]HONG XZ, LI LD, WU LM.Effects of fenofibrate andxuezhikang on high-fat diet-induced nonalcoholic fatty liver disease[J].Clin Exp Pharmacol Physiol, 2007, 34 (2) :27-35. [43]FABBRINI E, MOHAMMED BS, KORENBLAT KM, et al.Effect offenofibrate and niacin on intrahepatic triglyceride content, very lowdensity lipoprotein kinetics, and insulin action in obese subjects with nonalcoholic fatty liver disease[J].J Clin Endocrinol Metab, 2010, 95 (6) :2727-2735. [44]FERNANDEZ-MITANDA C, PEREZ-CARREARA M, COBLINA F, et al.A pilot trial of fenofibrate for the treatment of non-alcoholic fatty liver disease[J].Dig Liver Dis, 2008, 40 (3) :200-205. [45]REINER Z, CATAPANO AL, BACKER G, et al.ESC/EAS Guidelinesfor the management of dyslipidaemias:the Task Force for the management of dyslipidaemias of the European Society of Cardiology (ESC) and the European Atherosclerosis Society (EAS) [J].Eur Heart J, 2011, 32 (14) :1769-1818. [46]BELLOSTA S, CORSINI A.Statin drug interactions and related adverse reactions[J].Expert Opin Drug Saf, 2012, 11 (6) :933-946. [47]DESAI CS, MARTIN SS, BLUMENTHAL RS.Non-cardiovascular effects associated with statins[J].BMJ, 2014, 349:g3743. [48]YOUNOSZAI Z, LI Z, STEPANOVA M, et al.Statin use is not associated with liver related mortality[J].Ann Hepatol, 2013, 13 (1) :84-90. [49]DEMYEN M, ALKHALLOUFI K, PYRSOPOULOS NT.Lipidlowering agents and hepatotoxicity[J].Clin Liver Dis, 2013, 17 (4) :699-714. [50]KIM RG, LOOMBA R, PROKOP LJ, et al.Statin use and risk of cirrhosis and related complications in patients with chronic liverdiseases:a systematic review and meta-analysis[J].Clin Gastroenterol Hepatol, 2017.[Epub ahead of print]. [51]CHATRATH H, VUPPALANCHI R, CHALASNI N.Dyslipidemia in patients with nonalcoholic fatty liver disease[J].Semin Liver Dis, 2012, 32 (1) :22-29. [52]LIU T, ZHANG L, FAN JG, et al.An excerpt of non-alcoholic fatty liver disease (NAFLD) :assessment and management (NICEguidelines in 2016) [J].J Clin Hepatol, 2016, 32 (11) :2036-2038. [53]SARGES P, STEINBERG JM, LEWIS JH.Drug-induced liver injury:high lights from a review of the 2015 literature[J].Drug Saf, 2016, 39 (9) :801-821. [54]BAYS H, COHEN DE, CHALASAI N, et al.An assessment by the Statin Liver Safety Task Force:2014 update[J].J Clin Lipidol, 2014, 8 (3 Suppl) :47-57. [55]Group for Chinese expert consensus on use of statins in elderly patients with dyslipidemia.Chinese expert consensus on use of statins in elderly patients with dyslipidemia[J].Chin J Intern Med, 2015, 54 (5) :467-477.
本文二维码
计量
- 文章访问数: 1536
- HTML全文浏览量: 42
- PDF下载量: 357
- 被引次数: 0