Tanaka Naoki, Sano Kenji, Horiuchi Akira, Tanaka Eiji, Kiyosawa Kendo, Aoyama Toshifumi
Department of Metabolic Regulation, Shinshu University Graduate School of Medicine, Asahi, Matsumoto, Japan.
J Clin Gastroenterol. 2008 Apr;42(4):413-8. doi: 10.1097/MCG.0b013e31815591aa.
Recent studies have demonstrated that n-3 polyunsaturated fatty acids ameliorate nonalcoholic fatty liver disease. Although eicosapentaenoic acid (EPA), one of the major components of n-3 polyunsaturated fatty acids, is widely used as an antilipidemic agent, its single efficacy for nonalcoholic steatohepatitis (NASH) remains unclear. As such, we aimed to evaluate the efficacy and safety of EPA on 23 biopsy-proven NASH patients in a pilot trial. Highly purified EPA (2700 mg/d) was administered for 12 months and efficacy was assessed by biochemical parameters and liver histology. All patients completed the treatment with no adverse events, indicating acceptable tolerance to the treatment. After 12 months, serum alanine aminotransferase levels were significantly improved (from 79+/-36 to 50+/-20 U/L), and serum free fatty acids, plasma soluble tumor necrosis factor receptor 1 and 2 levels, and serum ferritin and thioredoxin levels, which may reflect hepatic oxidative stress, were significantly decreased. Body weight, blood glucose, insulin, and adiponectin concentrations remained unchanged. Seven of the 23 patients consented to undergo posttreatment liver biopsy, which showed improvement of hepatic steatosis and fibrosis, hepatocyte ballooning, and lobular inflammation in 6 patients. In conclusion, EPA treatment seems to be safe and efficacious for patients with NASH, largely due to its anti-inflammatory and antioxidative properties. To confirm these results, appropriately powered, controlled trials are needed.
近期研究表明,n-3多不饱和脂肪酸可改善非酒精性脂肪性肝病。虽然n-3多不饱和脂肪酸的主要成分之一二十碳五烯酸(EPA)被广泛用作抗血脂药,但其对非酒精性脂肪性肝炎(NASH)的单一疗效仍不明确。因此,我们旨在通过一项试点试验评估EPA对23例经活检证实的NASH患者的疗效和安全性。给予高纯度EPA(2700毫克/天),持续12个月,并通过生化参数和肝脏组织学评估疗效。所有患者均完成治疗,未出现不良事件,表明对该治疗的耐受性良好。12个月后,血清丙氨酸氨基转移酶水平显著改善(从79±36降至50±20 U/L),血清游离脂肪酸、血浆可溶性肿瘤坏死因子受体1和2水平以及可能反映肝脏氧化应激的血清铁蛋白和硫氧还蛋白水平均显著降低。体重、血糖、胰岛素和脂联素浓度保持不变。23例患者中有7例同意接受治疗后的肝脏活检,结果显示6例患者的肝脂肪变性、纤维化、肝细胞气球样变和小叶炎症有所改善。总之,EPA治疗对NASH患者似乎是安全有效的,这主要归功于其抗炎和抗氧化特性。为证实这些结果,需要进行适当规模的对照试验。