肝脏疾病中的他汀类药物：不仅预防心血管事件

StephenW

Editorial
Statins in liver disease: not only prevention of cardiovascular events
Antonio Magan-Fernandez ORCID Icon, Manfredi Rizzo ORCID Icon, Giuseppe Montalto ORCID Icon & Giulio Marchesini
Pages 743-744 | Received 02 Apr 2018, Accepted 14 May 2018, Accepted author version posted online: 17 May 2018, Published online: 24 May 2018

    Download citation https://doi.org/10.1080/17474124.2018.1477588

KEYWORDS: Fatty liver, cardiovascular risk, hydroxymethylglutaryl-CoA reductase inhibitors, non-alcoholic fatty liver disease, fatty liver, drug safety

Statins are lipid-lowering agents and one of the most prescribed drugs worldwide. Their main mechanism of action – inhibition of the mevalonate pathway through an effect on hydroxy-methylglutaryl CoA reductase, thus affecting the synthesis of cholesterol in the liver – makes this class of drugs pivotal in primary and secondary prevention of cardiovascular risk, as extensively demonstrated in large prospective, randomized controlled trials. Along the years, we learned that the lower the better, and LDL-cholesterol targets have been progressively reduced to values ≤70 mg/dL for secondary prevention or in the presence of diabetes.

The use of statins in patients with liver disease has long been limited by concern for their potential hepatotoxicity, raised by anecdotal evidence of raised liver enzymes following their use, or possible trapping of lipids in the liver. Statins metabolism occurs in the liver and statin intake has been associated with higher transaminase levels [1 Tziomalos K, Athyros VG, Paschos P, et al. Nonalcoholic fatty liver disease and statins. Metabolism. 2015;64(10):1215–1223.[Crossref], [PubMed], [Web of Science ®], [Google Scholar]]. In 2006, an extensive analysis of the Dallas Heart Study suggested that no harm was to be expected for the use of statins in subjects with liver disease, also including patients with hepatic steatosis [2 Browning JD. Statins and hepatic steatosis: perspectives from the Dallas Heart Study. Hepatology. 2006;44(2):466–471.[Crossref], [PubMed], [Web of Science ®], [Google Scholar]], and in a large practice-based analysis, patients with elevated liver enzymes were not at higher risk of statin hepatotoxicity [3 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.[Crossref], [PubMed], [Web of Science ®], [Google Scholar]]. In a comprehensive review, Bjornsson et al. reported that statin-related adverse events are very rare, although potentially severe. Both atorvastatin and simvastatin were associated with fatal outcomes, whereas no fatality was reported with rosuvastatin, suggesting a safer profile of novel statins [4 Bjornsson ES. Hepatotoxicity of statins and other lipid-lowering agents. Liver Int. 2017;37(2):173–178.[Crossref], [PubMed], [Web of Science ®], [Google Scholar]]. This analysis was further supported by a Cochrane Systematic Review in 2013, confirming that statins should be used, independently of any underlying liver disease, since the control of cardiovascular risk remains pivotal to reduce comorbidity [5 Eslami L, Merat S, Malekzadeh R, et al. Statins for non-alcoholic fatty liver disease and non-alcoholic steatohepatitis. Cochrane Database Syst Rev. 2013;27(12):CD008623.[PubMed], [Web of Science ®], [Google Scholar]]. This is mainly the case of subjects with both alcoholic and nonalcoholic fatty liver disease (AFLD and NAFLD), frequently associated with the metabolic syndrome and cardiovascular risk.

Several prospective studies and meta-analyses followed to support a more extensive use of statins, particularly in the NAFLD area. In the present issue of Expert Review of Gastroenterology & Hepatology, Imprialos et al. review the available evidence about statins and NAFLD, discussing the positive effects, possibly outweighing the reduction in cardiovascular risk and moving statins as a possible therapeutic option for liver disease itself [6 Imprialos KP, Stavropoulos K, Doumas M, et al. The potential role of statins in treating liver disease. Expert Rev Gastroenterol Hepatol. 2018;12(4):331–339.[Taylor & Francis Online], [Web of Science ®], [Google Scholar]]. A few comments about this relevant issue might be of interest.

Nonalcoholic fatty liver, i.e. the accumulation of lipids in hepatocytes above the physiologic threshold of 5% in the absence of significant alcohol intake (limits: 20 g/day in females, 30 g/day in males), occurs in nearly 25% of adults worldwide, but in nearly 75% of subjects with obesity and over 50% of cases with type 2 diabetes [7 Younossi Z, Anstee QM, Marietti M, et al. Global burden of NAFLD and NASH: trends, predictions, risk factors and prevention. Nat Rev Gastroenterol Hepatol. 2018;15(1):11–20.[Crossref], [PubMed], [Web of Science ®], [Google Scholar]]. In approximately 10% of cases with fatty liver the disease progresses to hepatic necroi\nflammation and fibrosis (nonalcoholic steatohepatitis – NASH), cirrhosis (NASH – cirrhosis), and eventually to hepatocellular carcinoma (HCC). The overall prevalence of disease is expected to increase further, due to the obesity epidemics, and NAFLD is now the second leading cause of liver transplantation in the United States [8 Wong RJ, Aguilar M, Cheung R, et al. Nonalcoholic steatohepatitis is the second leading etiology of liver disease among adults awaiting liver transplantation in the United States. Gastroenterology. 2015;148(3):547–555.[Crossref], [PubMed], [Web of Science ®], [Google Scholar]]. However, in long-term follow-up studies, fatal cardiovascular events are the most common causes of NASH-related mortality [9 Ekstedt M, Franzen LE, Mathiesen UL, et al. Long-term follow-up of patients with NAFLD and elevated liver enzymes. Hepatology. 2006;44(4):865–873.[Crossref], [PubMed], [Web of Science ®], [Google Scholar]], driven by type 2 diabetes mellitus (T2DM), metabolic syndrome, with increased levels of small dense atherogenic lipoprotein subfractions [10 Sonmez A, Nikolic D, Dogru T, et al. Low- and high-density lipoprotein subclasses in subjects with nonalcoholic fatty liver disease. J Clin Lipidol. 2015;9(4):576–582.[Crossref], [PubMed], [Web of Science ®], [Google Scholar]] and diffuse atherosclerotic lesions [11 Purnak T, Efe C, Beyazit Y, et al. Recent insights into the relationship between inflammatory liver diseases and atherosclerosis. J Investig Med. 2011;59(6):904–911.[Crossref], [PubMed], [Web of Science ®], [Google Scholar]], and requiring intensive treatment. This is the rationale for statin use in this population, but what about their effects on the liver?

The initial evidence for a beneficial effect of statins on liver function came from epidemiological studies, where statin use was associated with reduced risk of ultrasonography- and/or histologically-assessed NAFLD/NASH [12 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.[Crossref], [PubMed], [Web of Science ®], [Google Scholar],13 Bril F, Portillo Sanchez P, Lomonaco R, et al. Liver safety of statins in prediabetes or T2DM and nonalcoholic steatohepatitis: post hoc analysis of a randomized trial. J Clin Endocrinol Metab. 2017;102(8):2950–2961.[Crossref], [PubMed], [Web of Science ®], [Google Scholar]], also in the presence of diabetes, where the use of statins reduced the risk of both NASH and severe fibrosis [14 Nascimbeni F, Aron-Wisnewsky J, Pais R, et al. Statins, antidiabetic medications and liver histology in patients with diabetes with non-alcoholic fatty liver disease. BMJ Open Gastroenterol. 2016;3(1):e000075.[Crossref], [PubMed], [Web of Science ®], [Google Scholar]]. Atorvastatin reduced the expression of perilipin 5 in hepatocytes, contributing to increased lipolysis and reduced triglyceride accumulation through protein kinase A phosphorylation [15 Gao X, Nan Y, Zhao Y, et al. Atorvastatin reduces lipid accumulation in the liver by activating protein kinase A-mediated phosphorylation of perilipin 5. Biochim Biophys Acta. 2017;1862(12):1512–1519.[Crossref], [PubMed], [Web of Science ®], [Google Scholar]]. A systematic review and meta-analysis confirmed that statins were associated with lower risk of advanced liver disease and mortality, and might also reduce portal hypertension, stopping disease progression and even promoting fibrosis regression [16 Kim RG, Loomba R, Prokop LJ, et al. Statin use and risk of cirrhosis and related complications in patients with chronic liver diseases: a systematic review and meta-analysis. Clin Gastroenterol Hepatol. 2017;15(10):1521–1530 e1528.[Crossref], [PubMed], [Web of Science ®], [Google Scholar]]. Simvastatin acted as Krüppel-like factor 2 inducer, improving cell viability, ameliorating liver injury in ischemia/reperfusion and improving fibrosis, endothelial dysfunction and portal hypertension in both animal and human models of liver sinusoidal endothelial and stellate cells [17 Guixe-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.[Crossref], [PubMed], [Web of Science ®], [Google Scholar],18 Marrone G, Maeso-Diaz R, Garcia-Cardena G, et al. KLF2 exerts antifibrotic and vasoprotective effects in cirrhotic rat livers: behind the molecular mechanisms of statins. Gut. 2015;64(9):1434–1443.[Crossref], [PubMed], [Web of Science ®], [Google Scholar]]. Acute pretreatment with simvastatin of the donor protected liver tissue and cells during cold storage for posterior transplantation [19 Gracia-Sancho J, Garcia-Caldero H, Hide D, et al. Simvastatin maintains function and viability of steatotic rat livers procured for transplantation. J Hepatol. 2013;58(6):1140–1146.[Crossref], [PubMed], [Web of Science ®], [Google Scholar]]. The pleiotropic effects of statins also extend to anti-fibrotic action, as well as to better response to treatment for chronic hepatitis C and reduced risk and better survival rate of hepatocellular carcinoma [20 Janicko M, Drazilova S, Pella D, et al. Pleiotropic effects of statins in the diseases of the liver. World J Gastroenterol. 2016;22(27):6201–6213.[Crossref], [PubMed], [Web of Science ®], [Google Scholar]]. Unfortunately, only few and limited studies were specifically designed to test the use of statins in the treatment of NAFLD and were inconclusive. Larger studies would be difficult to arrange, particularly in diabetes-associated NAFLD, considering that the use of statins carries an increased risk of new onset diabetes [21 Katsiki N, Athyros VG, Karagiannis A, et al. Statins and type 2 diabetes mellitus: an update after 1 year. Curr Pharm Des. 2016;22(18):2723–2725.[Crossref], [PubMed], [Web of Science ®], [Google Scholar]]. Several novel drugs are on the horizon for treatment in NAFLD/NASH, and are being tested in phases 2–3 trials in subjects with/without diabetes in order to reduce hepatic necroinflammation, without worsening of fibrosis [22 Brodosi L, Marchignoli F, Petroni ML, et al. NASH: a glance at the landscape of pharmacological treatment. Ann Hepatol. 2016;15(5):673–681.[PubMed], [Web of Science ®], [Google Scholar]]. No matter they may be confidently associated with statins to achieve better hepatic and cardiovascular outcomes. NAFLD Clinical Practice Guidelines, jointly published by the European Associations of Liver Disease, Diabetes and Obesity (EASL-EASD-EASO) strongly recommend strict control of cardiovascular risk in patients with NAFLD/NASH [23 European Association for the Study of the Liver, European Association for the Study of Diabetes, European Association for the Study of Obesity. EASL-EASD-EASO Clinical Practice Guidelines for the management of non-alcoholic fatty liver disease. Diabetologia. 2016;59(6):1121–1140.[Crossref], [PubMed], [Web of Science ®], [Google Scholar]], and statins remain a safe, effective and pivotal therapeutic option to this goal.
Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

StephenW

社论
肝脏疾病中的他汀类药物：不仅预防心血管事件
Antonio Magan-Fernandez ORCID Icon，Manfredi Rizzo ORCID Icon，Giuseppe Montalto ORCID Icon＆Giulio Marchesini
第743-744页|收到2018年4月2日，接受2018年5月14日，接受作者版本在线发布：2018年5月17日，在线发布：2018年5月24日

    下载引文https://doi.org/10.1080/17474124.2018.1477588

关键词：脂肪肝，心血管风险，羟甲基戊二酰辅酶A还原酶抑制剂，非酒精性脂肪肝，脂肪肝，药物安全性

他汀类药物是降脂药，也是全球处方药最多的药物之一。它们的主要作用机制 - 通过对羟甲基戊二酰辅酶A还原酶的作用抑制甲羟戊酸途径，从而影响肝脏中胆固醇的合成 - 使得这类药物在心血管风险的一级和二级预防中起关键作用，如大型前瞻性随机对照试验。多年来，我们了解到越低越好，LDL胆固醇目标逐渐降低至≤70mg/ dL，用于二级预防或糖尿病。

他汀类药物在肝病患者中的使用长期受到关注其潜在肝毒性的限制，这是由于使用后肝酶升高或肝脏中脂质可能被捕获的传闻证据所致。他汀类药物代谢发生在肝脏，他汀类药物摄入量与较高的转氨酶水平有关[1 Tziomalos K，Athyros VG，Paschos P，et al。非酒精性脂肪肝和他汀类药物。代谢。 2015; 64（10）：1215-1223。[Crossref]，[PubMed]，[Web ofScience®]，[Google Scholar]]。 2006年，对达拉斯心脏研究的广泛分析表明，对于肝病患者使用他汀类药物也没有任何危害，包括肝脏脂肪变性患者[2 Browning JD。他汀类药物和肝脏脂肪变性：达拉斯心脏研究的观点。肝病。 2006; 44（2）：466-471。[Crossref]，[PubMed]，[Web ofScience®]，[Google Scholar]]，在一项基于实践的大型分析中，肝酶升高的患者不高他汀类药物肝毒性的风险[3 Chalasani N，Aljadhey H，Kesterson J，et al。肝酶升高的患者他汀类药物肝毒性的风险不高。消化内科。 2004; 126（5）：1287-1292。[Crossref]，[PubMed]，[Web ofScience®]，[Google Scholar]]。在综合评论中，Bjornsson等。据报道，他汀类药物相关的不良事件非常罕见，尽管可能很严重。阿托伐他汀和辛伐他汀均与致命结果相关，而罗苏伐他汀未报告死亡，表明新型他汀类药物更安全[4 Bjornsson ES。他汀类药物和其他降脂药的肝毒性。肝脏国际2017; 37（2）：173-178。[Crossref]，[PubMed]，[Web ofScience®]，[Google Scholar]]。 2013年Cochrane系统评价进一步支持了这一分析，证实应使用他汀类药物，不论任何潜在的肝脏疾病，因为控制心血管风险仍然是降低合并症的关键[5 Eslami L，Merat S，Malekzadeh R，et人。他汀类药物为非酒精性脂肪性肝病和非酒精性脂肪性肝炎。 Cochrane Database Syst Rev. 2013; 27（12）：CD008623。[PubMed]，[Web ofScience®]，[Google Scholar]]。这主要是患有酒精性和非酒精性脂肪性肝病（AFLD和NAFLD）的受试者，通常与代谢综合征和心血管风险相关。

随后进行了几项前瞻性研究和荟萃分析，以支持更广泛地使用他汀类药物，特别是在NAFLD领域。在本期“胃肠病学和肝病学专家评论”中，Imprialos等。回顾有关他汀类药物和NAFLD的现有证据，讨论其可能超过心血管风险降低的正面影响，并将他汀类药物作为肝病本身可能的治疗选择[6 Imprialos KP，Stavropoulos K，Doumas M，et al。他汀类药物在治疗肝病中的潜在作用。专家Rev Gastroenterol Hepatol。 2018; 12（4）：331-339。[Taylor＆Francis Online]，[Web ofScience®]，[Google Scholar]]。关于这个相关问题的一些评论可能会引起关注。
非酒精性脂肪肝，即在没有显着酒精摄入的情况下，肝细胞中脂质的积累高于5％的生理阈值（限制：女性为20克/天，男性为30克/天），发生在将近25％的成人中世界范围内，但近75％的肥胖受试者和超过50％的2型糖尿病患者[7 Younossi Z，Anstee QM，Marietti M，et al。 NAFLD和NASH的全球负担：趋势，预测，风险因素和预防。 Nat Rev Gastroenterol Hepatol。 2018; 15（1）：11-20。[Crossref]，[PubMed]，[Web ofScience®]，[Google Scholar]]。大约10％的脂肪肝病例发展为肝脏坏死性炎症和纤维化（非酒精性脂肪性肝炎 - NASH），肝硬化（NASH - 肝硬化），最终发展为肝细胞癌（HCC）。由于肥胖的流行，预计疾病的总体患病率会进一步增加，而NAFLD现在是美国肝移植的第二大原因[8 Wong RJ，Aguilar M，Cheung R，et al。非酒精性脂肪性肝炎是美国等待肝移植的成年人中肝病的第二大病因。消化内科。 2015; 148（3）：547-555。[Crossref]，[PubMed]，[Web ofScience®]，[Google Scholar]]。然而，在长期随访研究中，致命的心血管事件是导致NASH相关死亡的最常见原因[9 Ekstedt M，Franzen LE，Mathiesen UL，et al。 NAFLD和肝酶升高患者的长期随访。肝病。 2006; 44（4）：865-873。[Crossref]，[PubMed]，[Web ofScience®]，[Google Scholar]]，由2型糖尿病（T2DM），代谢综合征驱动，小水平增加致密致动脉粥样硬化脂蛋白亚组分[10 Sonmez A，Nikolic D，Dogru T，et al。非酒精性脂肪性肝病患者的低密度和高密度脂蛋白亚类。 J Clin Lipidol。 2015; 9（4）：576-582。[Crossref]，[PubMed]，[Web ofScience®]，[Google Scholar]]和弥漫性动脉粥样硬化病变[11 Purnak T，Efe C，Beyazit Y，et al。最近对炎性肝病与动脉粥样硬化之间关系的见解。 J Investig Med。 2011; 59（6）：904-911。[Crossref]，[PubMed]，[Web ofScience®]，[Google Scholar]]，并要求强化治疗。这是他汀类药物在这个人群中使用的基本原理，但它们对肝脏有何影响呢？
他汀类药物对肝功能有益作用的初步证据来自流行病学研究，其中他汀类药物的使用与降低的超声检查风险和/或组织学评估的NAFLD / NASH相关[12 Dongiovanni P，Petta S，Mannisto V，et al 。他汀类药物使用和非酒精性脂肪性肝炎患者。 J Hepatol。 2015; 63（3）：705-712。[Crossref]，[PubMed]，[Web ofScience®]，[Google Scholar]，13 Bril F，Portillo Sanchez P，Lomonaco R，et al。他汀类药物在前驱糖尿病或T2DM和非酒精性脂肪性肝炎中的肝脏安全性：随机试验的事后分析。 J Clin Endocrinol Metab。 2017; 102（8）：2950-2961。[Crossref]，[PubMed]，[Web ofScience®]，[Google Scholar]]，也存在糖尿病，使用他汀类药物可降低NASH的风险和严重纤维化[14 Nascimbeni F，Aron-Wisnewsky J，Pais R，et al。他汀类药物，抗糖尿病药物和肝脏组织学在患有非酒精性脂肪性肝病的糖尿病患者中。 BMJ开放胃肠道。 2016; 3（1）：e000075。[Crossref]，[PubMed]，[Web ofScience®]，[Google Scholar]]。阿托伐他汀降低肝细胞中perilipin 5的表达，通过蛋白激酶A磷酸化促进脂解作用和降低甘油三酯积累[15 Gao X，Nan Y，Zhao Y，et al。阿托伐他汀通过激活蛋白激酶A介导的perilipin磷酸化来减少肝脏中的脂质积累.Biochim Biophys Acta。 2017; 1862（12）：1512-1519。[Crossref]，[PubMed]，[Web ofScience®]，[Google Scholar]]。系统评价和荟萃分析证实他汀类药物与晚期肝病和死亡风险较低有关，也可能降低门静脉高压，阻止疾病进展，甚至促进纤维化消退[16 Kim RG，Loomba R，Prokop LJ，et al 。他汀类药物的使用和慢性肝病患者肝硬化和相关并发症的风险：系统评价和荟萃分析。 Clin Gastroenterol Hepatol。 2017; 15（10）：1521-1530 e1528。[Crossref]，[PubMed]，[Web ofScience®]，[Google Scholar]]。辛伐他汀作为Krüppel样因子2诱导剂，改善细胞活力，改善缺血/再灌注时肝损伤，改善肝窦内皮细胞和星状细胞的动物和人体模型中的纤维化，内皮功能障碍和门静脉高压[17 Guixe-Muntet S， De Mesquita FC，Vila S，et al。自噬和KLF2之间的串扰决定了急性肝损伤中的内皮细胞表型和微血管功能。 J Hepatol。 2017; 66（1）：86-94。[Crossref]，[PubMed]，[Web ofScience®]，[Google Scholar]，18 Marrone G，Maeso-Diaz R，Garcia-Cardena G，et al。 KLF2在肝硬化大鼠肝脏中发挥抗纤维化和血管保护作用：他汀类药物的分子机制背后。肠道。 2015; 64（9）：1434-1443。[Crossref]，[PubMed]，[Web ofScience®]，[Google Scholar]]。急性预处理用供体的辛伐他汀保护肝组织和细胞在冷藏期间进行后移植[19 Gracia-Sancho J，Garcia-Caldero H，Hide D，et al。辛伐他汀维持用于移植的脂肪性大鼠肝脏的功能和活力。 J Hepatol。 2013; 58（6）：1140-1146。[Crossref]，[PubMed]，[Web ofScience®]，[Google Scholar]]。他汀类药物的多效作用也延伸到抗纤维化作用，以及对慢性丙型肝炎治疗的更好反应，降低肝细胞癌的风险和更好的存活率[20 Janicko M，Drazilova S，Pella D，et al。他汀类药物对肝脏疾病的多效作用。 World J Gastroenterol。 2016; 22（27）：6201-6213。[Crossref]，[PubMed]，[Web ofScience®]，[Google Scholar]]。不幸的是，只有少数和有限的研究专门用于检测他汀类药物在NAFLD治疗中的应用，尚无定论。考虑到他汀类药物的使用会增加患新发糖尿病的风险，因此难以安排更大规模的研究，尤其是糖尿病相关的NAFLD [21 Katsiki N，Athyros VG，Karagiannis A，et al。他汀类药物和2型糖尿病：1年后更新。 Curr Pharm Des。 2016; 22（18）：2723-2725。[Crossref]，[PubMed]，[Web ofScience®]，[Google Scholar]]。几种新型药物即将在NAFLD / NASH治疗中出现，并且正在为有/无糖尿病的受试者进行2-3期试验，以减少肝脏坏死性炎症，而不会使纤维化恶化[22 Brodosi L，Marchignoli F，Petroni ML等人。 NASH：瞥一眼药物治疗的景观。安·赫普托尔。 2016; 15（5）：673-681。[PubMed]，[Web ofScience®]，[Google Scholar]]。无论他们是否可能与他汀类药物相关联，以实现更好的肝脏和心血管结果。由欧洲肝病，糖尿病和肥胖协会（EASL-EASD-EASO）联合出版的NAFLD临床实践指南强烈建议严格控制NAFLD / NASH患者的心血管风险[23欧洲研究协会糖尿病和肥胖（EASL-EASD-EASO）强烈建议严格控制NAFLD / NASH患者的心血管风险[23欧洲肝脏研究协会，欧洲糖尿病研究协会，欧洲肥胖研究协会。 EASL-EASD-EASO非酒精性脂肪性肝病管理临床实践指南。糖尿病学。 2016; 59（6）：1121-1140。[Crossref]，[PubMed]，[Web ofScience®]，[Google Scholar]]和他汀类药物仍然是实现这一目标的安全，有效和关键的治疗选择。
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除与公开的文件中所述的主题或材料有财务利益或财务冲突之外，作者与任何组织或实体没有相关联系或财务参与。 本手稿的同行评审员没有相关的财务或其他关系要披露。

王震宇

StephenW 发表于 2018-7-21 19:54
社论
肝脏疾病中的他汀类药物：不仅预防心血管事件
Antonio Magan-Fernandez ORCID Icon，Manfredi Rizzo O ...

大傻子呀大傻子！
你吃饱了撑的没事干啦！
你怎么又折腾起他汀来了？
这类破药有什么可研究的，净惹事！！

StephenW

回复 王震宇 的帖子

如果你不知道他汀药对高胆固醇，脂肪肝和有纤维化的hbv患者的潜在用处, 这是你自己的问题.

王震宇

脂肪肝只是脂代谢异常的结果，只是个全身疾病的局部表现，把焦点只放在肝上，而且他汀只管抑制脂代谢，把灾难拥堵在上游，岂不是更可怕么？

王震宇

顺便告诉你，我们一家老老少少全都脂代谢异常，但没有一个吃他汀药的。

王震宇

烤不吃盐去控制血压，靠不吃饭去控制血糖，还有比这更愚蠢的妙招么？

newchinabok

王震宇 发表于 2018-7-21 23:50
烤不吃盐去控制血压，靠不吃饭去控制血糖，还有比这更愚蠢的妙招么？

靠不吃拉米，去控制乙肝DNA。老王，我这招妙不妙？

StephenW

王震宇 发表于 2018-7-21 23:48
顺便告诉你，我们一家老老少少全都脂代谢异常，但没有一个吃他汀药的。
...

祝他们身体健康.

MP4

王震宇 发表于 2018-7-21 23:48
顺便告诉你，我们一家老老少少全都脂代谢异常，但没有一个吃他汀药的。
...

你女儿还好不？小孩呢？