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降脂治疗在脂肪肝疾病管理中是否发挥作用?

Is there a role of lipid-lowering therapies in the management of fatty liver disease?

作者信息

Tzanaki Ismini, Agouridis Aris P, Kostapanos Michael S

机构信息

School of Medicine, European University Cyprus, Nicosia, Cyprus, Nicosia 2404, Cyprus.

School of Medicine, European University Cyprus, Nicosia 2404, Cyprus.

出版信息

World J Hepatol. 2022 Jan 27;14(1):119-139. doi: 10.4254/wjh.v14.i1.119.

Abstract

Atherogenic dyslipidemia is characterized by increased triglyceride-rich lipoproteins and low high-density lipoprotein cholesterol concentrations. It is highly prevalent in non-alcoholic fatty liver disease (NAFLD) and contributes to the increased cardiovascular risk associated with this condition. Alongside insulin resistance it plays an important pathogenetic role in NAFLD/non-alcoholic steatohepatitis (NASH) development and progression. It has been shown that cholesterol-lowering reduces cardiovascular risk more in NAFLD non-NAFLD high-risk individuals. This evidence highlights the importance of effective lipid modulation in NAFLD. In this narrative review the effects of the most commonly used lipid-lowering therapies on liver outcomes alongside their therapeutic implications in NAFLD/NASH are critically discussed. Preclinical and clinical evidence suggests that statins reduce hepatic steatosis, inflammation and fibrosis in patients with NAFLD/NASH. Most data are derived from observational and small prospective clinical studies using changes in liver enzyme activities, steatosis/fibrosis scores, and imaging evidence of steatosis as surrogates. Also, relevant histologic benefits were noted in small biopsy studies. Atorvastatin and rosuvastatin showed greater benefits, whereas data for other statins are scarce and sometimes conflicting. Similar studies to those of statins showed efficacy of ezetimibe against hepatic steatosis. However, no significant anti-inflammatory and anti-fibrotic actions of ezetimibe have been shown. Preclinical studies showed that fibrates through peroxisome proliferator-activated receptor (PPAR)α activation may have a role in NAFLD prevention and management. Nevertheless, no relevant benefits have been noted in human studies. Species-related differences in PPARα expression and its activation responsiveness may help explain this discrepancy. Omega-3 fatty acids reduced hepatic steatosis in numerous heterogeneous studies, but their benefits on hepatic inflammation and fibrosis have not been established. Promising preliminary data for the highly purified eicosapentaenoic acid require further confirmation. Observational studies suggest that proprotein convertase subtilisin/kexin9 inhibitors may also have a role in the management of NAFLD, though this needs to be established by future prospective studies.

摘要

致动脉粥样硬化性血脂异常的特征是富含甘油三酯的脂蛋白增加和高密度脂蛋白胆固醇浓度降低。它在非酒精性脂肪性肝病(NAFLD)中高度普遍,并导致与该疾病相关的心血管风险增加。除胰岛素抵抗外,它在NAFLD/非酒精性脂肪性肝炎(NASH)的发生和发展中起重要的致病作用。研究表明,在NAFLD和非NAFLD高危个体中,降低胆固醇对降低心血管风险的作用更大。这一证据凸显了在NAFLD中进行有效脂质调节的重要性。在这篇叙述性综述中,批判性地讨论了最常用的降脂疗法对肝脏结局的影响及其在NAFLD/NASH中的治疗意义。临床前和临床证据表明,他汀类药物可减轻NAFLD/NASH患者的肝脂肪变性、炎症和纤维化。大多数数据来自观察性研究和小型前瞻性临床研究,这些研究使用肝酶活性变化、脂肪变性/纤维化评分以及脂肪变性的影像学证据作为替代指标。此外,在小型活检研究中也注意到了相关的组织学益处。阿托伐他汀和瑞舒伐他汀显示出更大的益处,而其他他汀类药物的数据稀少且有时相互矛盾。与他汀类药物类似的研究表明依折麦布对肝脂肪变性有效。然而,尚未显示依折麦布有显著的抗炎和抗纤维化作用。临床前研究表明,贝特类药物通过激活过氧化物酶体增殖物激活受体(PPAR)α可能在NAFLD的预防和管理中发挥作用。然而,在人体研究中未观察到相关益处。PPARα表达及其激活反应性的物种相关差异可能有助于解释这种差异。在众多不同研究中,ω-3脂肪酸可减轻肝脂肪变性,但其对肝脏炎症和纤维化的益处尚未得到证实。高度纯化的二十碳五烯酸的有前景的初步数据需要进一步证实。观察性研究表明,前蛋白转化酶枯草溶菌素/kexin9抑制剂可能在NAFLD的管理中也发挥作用,不过这需要未来的前瞻性研究来证实。

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