Caldwell Stephen
GI/Hepatology Division, University of Virginia, Charlottesville, Virginia, USA.
Clin Mol Hepatol. 2017 Jun;23(2):103-108. doi: 10.3350/cmh.2017.0103. Epub 2017 May 10.
Non-alcoholic steatohepatitis (NASH) is the more aggressive form of non-alcoholic fatty liver disease (NAFLD). NASH can progress to hepatic fibrosis, cirrhosis, portal hypertension and primary liver cancer. Therapy is evolving with a substantial number of trials of promising new agents now in progress. In this article however, we will examine data for several older forms of therapy which have been fairly extensively studied over the years: Polyunsaturated Fatty Acid (PUFA) supplements, vitamin E, insulin sensitizing agents with a focus on pioglitazone and statin agents. Early interest in PUFA derived from their potential benefit in cardio-metabolic disease and the close association of NAFLD/NASH with Metabolic Syndrome. Results have been variable although most studies show reduction of liver fat without other major effects and their effects are influenced by concomitant weight loss and underlying genetic factors. Vitamin E has had some efficacy in pediatric NASH but questionable efficacy in even mild NASH among adults. Pioglitazone has shown significant histological benefit in a number of trials but concern over side-effects (especially weight gain) have dampened enthusiasm. A newer insulin sensitizer, liraglutide, has also shown promise in a small randomized, controlled trial. Very limited data exists regarding the histological effects of the statins in NASH and these agents appear to be fairly neutral with neither clear cut benefit nor detriment. Their use is best guided by cardiovascular risks rather than liver histology.
非酒精性脂肪性肝炎(NASH)是非酒精性脂肪性肝病(NAFLD)中更具侵袭性的一种形式。NASH可进展为肝纤维化、肝硬化、门静脉高压和原发性肝癌。随着大量有前景的新型药物试验正在进行,治疗方法也在不断发展。然而,在本文中,我们将研究几种多年来已得到相当广泛研究的较老治疗方法的数据:多不饱和脂肪酸(PUFA)补充剂、维生素E、以吡格列酮为重点的胰岛素增敏剂和他汀类药物。早期对PUFA的兴趣源于其在心血管代谢疾病中的潜在益处以及NAFLD/NASH与代谢综合征的密切关联。尽管大多数研究表明肝脏脂肪减少但无其他主要影响,且其效果受体重减轻和潜在遗传因素的影响,结果存在差异。维生素E在儿童NASH中具有一定疗效,但在成人中即使是轻度NASH其疗效也存在疑问。吡格列酮在多项试验中显示出显著的组织学益处,但对副作用(尤其是体重增加)的担忧减弱了人们的热情。一种较新的胰岛素增敏剂利拉鲁肽在一项小型随机对照试验中也显示出前景。关于他汀类药物在NASH中的组织学作用的数据非常有限,这些药物似乎相当中性,既没有明显的益处也没有损害。它们的使用最好以心血管风险而非肝脏组织学为指导。