Departments of Gastroenterology and MetabolismExperimental Pathology and Tumor BiologyCell Biology and Anatomy, Nagoya City University Graduate School of Medical Sciences, Nagoya, Aichi, Japan.
Hepatol Res. 2011 Apr;41(4):375-85. doi: 10.1111/j.1872-034X.2010.00769.x. Epub 2011 Jan 30.
Non-alcoholic steatohepatitis (NASH) may progress to liver cirrhosis, and NASH patients with liver cirrhosis are at risk of developing hepatocellular carcinoma. Statins, 3-hydroxy-3-methyglutaryl-coenzyme A reductase inhibitors, are well known to reduce low-density lipoprotein cholesterol and reduce the incidence of coronary heart disease and other major vascular events by anti-inflammatory and antifibrotic effects, and antiproliferative properties in colorectal cancers have also been reported. Recently, statins have been reported to improve hepatic steatosis; however, the effect on fibrosis is controversial.
The effects of pitavastatin (one of the strongest statins) were examined using a choline-deficient L-amino acid-defined (CDAA) diet liver fibrosis model.
Pitavastatin significantly attenuated increases in serum aspartate aminotransferase, alanine aminotransferase, hepatic steatosis, oxidative stress, pre-neoplastic lesions (glutathione S-transferase placental form-positive lesions), expression of cytokines, such as tumor necrosis factor-α and transforming growth factor-β1, and the expression of tissue inhibitor of metalloproteinase-1, tissue inhibitor of metalloproteinase-2 and type I procollagen genes followed by attenuating fibrosis of the liver of CDAA-fed rats.
These results indicate that pitavastatin may inhibit steatosis, hepatic fibrosis and carcinogenesis in rat model of NASH.
非酒精性脂肪性肝炎（NASH）可能进展为肝硬化，NASH 合并肝硬化患者发生肝细胞癌的风险增加。他汀类药物，即 3-羟基-3-甲基戊二酰辅酶 A 还原酶抑制剂，通过抗炎和抗纤维化作用以及在结直肠癌中的抗增殖作用，众所周知可降低低密度脂蛋白胆固醇并降低冠心病和其他主要血管事件的发生率。最近，有报道称他汀类药物可改善肝脂肪变性；然而，其对纤维化的影响存在争议。
使用胆碱缺乏 L-氨基酸定义（CDAA）饮食肝纤维化模型检查了匹伐他汀（最强的他汀类药物之一）的作用。
匹伐他汀显著减弱了血清天冬氨酸转氨酶、丙氨酸转氨酶、肝脂肪变性、氧化应激、前肿瘤病变（谷胱甘肽 S-转移酶胎盘形式阳性病变）、细胞因子如肿瘤坏死因子-α和转化生长因子-β1 的表达以及组织抑制剂的表达。金属蛋白酶-1、金属蛋白酶-2 和 I 型前胶原基因的表达，从而减弱了 CDAA 喂养大鼠的肝纤维化。
这些结果表明，匹伐他汀可能抑制 NASH 大鼠模型中的脂肪变性、肝纤维化和癌变。
