Gradenigo Hospital, Turin, Italy.
Curr Pharm Des. 2013;19(29):5297-313.
This review is part of a special issue dealing with various aspects of non-alcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH). We will focus on promising treatments of NASH with antioxidants and drugs that interfere with lipid metabolism.The other therapies of interest, such as diet, behavioral changes, and insulin sensitizers are presented elsewhere. Oxidative stress is believed to play a key role in the pathogenesis of NASH and other liver diseases. Antioxidants aimed at improving chronic alcoholic or viral liver diseases have been an object of study for some time. However, only a few high quality, randomized, versus placebo-controlled, double-blinded trials have been carried out to assess these drugs. Vitamin E is currently the most widely assessed antioxidant. Several questions need to be answered, including long-term tolerance and efficacy of vitamin E in particular subsets, such as diabetes and NASH-related cirrhosis. Other antioxidants are promising, and should be assessed using the standards of evidence-based medicine. NAFLD frequently coexists with hyperlipidemia and carries an increased risk of cardiovascular disease (CVD). Furthermore, altered lipid metabolism is thought to be central to the pathogenesis of liver injury in NASH. Therefore, lipid-lowering drugs are attractive therapeutic tools in the treatment of NAFLD. Statins have ameliorated surrogate markers of steatosis in several randomized controlled trials, but their impact on liver histology is unknown. They have, however, been found to be the only class of lipid-lowering drugs that reduces cardiovascular risk in NAFLD. Preliminary evidence suggests that ezetimibe, an inhibitor of intestinal and hepatic cholesterol absorption, may improve liver histology, but its impact on the risk of CVD and on clinical outcome remains to be determined. Despite strong experimental evidence supporting the use of omega-3 polyunsaturated fatty acids in NAFLD, the studies published on humans have consisted of small sample sizes and had a number of methodological flaws, including the absence of post-treatment histology. Association of antioxidants and/or lipid-lowering drugs plus other drugs of interest in NASH, such as insulin sensitizers, warrant investigation. However, as promising as these drug treatments may continue to be, they should be associated with diet and modifications in lifestyle.
这篇综述是专门讨论非酒精性脂肪性肝病（NAFLD）和非酒精性脂肪性肝炎（NASH）各方面问题的特刊的一部分。我们将重点介绍抗氧化剂和干扰脂质代谢的药物治疗 NASH 的有前途的方法。其他有治疗意义的方法，如饮食、行为改变和胰岛素增敏剂，将在别处介绍。氧化应激被认为在 NASH 和其他肝病的发病机制中起关键作用。一段时间以来，人们一直在研究旨在改善慢性酒精性或病毒性肝病的抗氧化剂。然而，只有少数高质量的、随机的、安慰剂对照的、双盲试验被用于评估这些药物。维生素 E 是目前评估最多的抗氧化剂。需要回答几个问题，包括维生素 E 在某些特定亚组（如糖尿病和 NASH 相关肝硬化）中的长期耐受性和疗效。其他抗氧化剂也很有前途，应该使用循证医学的标准进行评估。NAFLD 常伴有高脂血症，增加了心血管疾病（CVD）的风险。此外，脂质代谢改变被认为是 NASH 中肝损伤发病机制的核心。因此，降脂药物是治疗 NAFLD 的有吸引力的治疗工具。他汀类药物在几项随机对照试验中改善了脂肪变性的替代标志物，但它们对肝组织学的影响尚不清楚。然而，它们已被发现是唯一一类能降低 NAFLD 患者心血管风险的降脂药物。初步证据表明，胆固醇吸收抑制剂依折麦布可能改善肝组织学，但它对 CVD 风险和临床结局的影响仍有待确定。尽管有强有力的实验证据支持在 NAFLD 中使用ω-3 多不饱和脂肪酸，但在人类中发表的研究样本量较小，并且存在许多方法学缺陷，包括缺乏治疗后组织学。在 NASH 中联合使用抗氧化剂和/或降脂药物以及其他有治疗意义的药物，如胰岛素增敏剂，值得研究。然而，这些药物治疗方法可能仍然很有前途，但它们应该与饮食和生活方式的改变相结合。
