Second Propedeutic Department of Internal Medicine, Medical School, Aristotle University of Thessaloniki, Hippocration Hospital, Thessaloniki, Greece.
Military Medical Department, Thessaloniki, Greece.
Curr Vasc Pharmacol. 2018;16(3):246-253. doi: 10.2174/1570161115666170621082910.
Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease (30% of the general population) and up to 40% of cases advance to the more severe form of the disease: nonalcoholic steatohepatitis (NASH), which is causally related to cirrhosis and cardiovascular disease (CVD). There is no generally accepted effective treatment for NAFLD/NASH. The joint guidelines of the European Association for the Study of the Liver (EASL), the European Association for the Study of Diabetes (EASD) and the European Association for the Study of Obesity (EASO) suggest the "off label" use of pioglitazone in patients without type 2 diabetes mellitus (T2DM) and pioglitazone in subjects with T2DM or vitamin E or their combination for the treatment of NASH; however pioglitazone has considerable limitations: weight gain, bone fractures in women, and heart failure. The aim of this narrative review is to assess the existing evidence supporting statin use for the treatment of NASH and the reduction of the high CVD risk of these patients. Animal data suggest that there is some benefit from statin use in liver histology in models of NASH. In humans, 3 post hoc analyses of randomised controlled trials (n=1,600, n=1,123, n=8,864) suggest that the use of atorvastatin (even in 80 mg/day) has a beneficial effect on NAFLD/NASH, in terms of liver enzyme reduction and ultrasonographic amelioration. Moreover, and most importantly, statin treatment halved CVD morbidity and mortality in statin-treated NAFLD/NASH patients compared with statin-treated participants with normal liver structure and function and reduced by 2/3rds CVD events in comparison with NAFLD/NASH patients that were not on a statin (90% of this population is not on statins because of the unjustified fear for liver damage). Three biopsy studies (n=20, n=107 and n=356) showed that statin treatment had a protective effect on steatosis, steatohepatitis and fibrosis. Data suggest that statin treatment in humans substantially improve or cure NAFLD/NASH, but above all substantially reduce CVD morbidity and mortality. Administration of potent statins appears safe and effective in saving lives in NAFLD/NASH patients.
非酒精性脂肪性肝病（NAFLD）是最常见的肝脏疾病（占普通人群的 30%），多达 40%的病例会发展为更严重的疾病：非酒精性脂肪性肝炎（NASH），它与肝硬化和心血管疾病（CVD）有因果关系。目前尚无普遍接受的有效治疗方法NAFLD/NASH。欧洲肝脏研究协会（EASL）、欧洲糖尿病研究协会（EASD）和欧洲肥胖研究协会（EASO）联合指南建议在没有 2 型糖尿病（T2DM）的患者中使用吡格列酮，在 T2DM 或维生素 E 或两者联合治疗 NASH 的患者中使用吡格列酮；然而，吡格列酮有相当大的局限性：体重增加、女性骨折和心力衰竭。本叙述性综述的目的是评估现有证据支持他汀类药物治疗 NASH 和降低这些患者的高 CVD 风险。动物数据表明，在 NASH 模型中，他汀类药物的使用在肝脏组织学上有一定的益处。在人类中，3 项随机对照试验（n=1600、n=1123、n=8864）的事后分析表明，阿托伐他汀（即使每天 80mg）的使用对 NAFLD/NASH 有有益的影响，可降低肝酶和改善超声表现。此外，最重要的是，与他汀类药物治疗的具有正常肝脏结构和功能的参与者相比，他汀类药物治疗的 NAFLD/NASH 患者的 CVD 发病率和死亡率减半，与未服用他汀类药物的 NAFLD/NASH 患者相比，CVD 事件减少 2/3（该人群中有 90%未服用他汀类药物，因为担心肝脏损伤而不合理）。3 项活检研究（n=20、n=107 和 n=356）表明，他汀类药物治疗对脂肪变性、脂肪性肝炎和纤维化有保护作用。数据表明，在人类中，他汀类药物治疗可显著改善或治愈 NAFLD/NASH，但最重要的是可显著降低 CVD 的发病率和死亡率。在 NAFLD/NASH 患者中，使用强效他汀类药物似乎可以安全有效地挽救生命。
