Resolution of non-alcoholic steatohepatitis by rosuvastatin monotherapy in patients with metabolic syndrome
Resolution of non-alcoholic steatohepatitis by rosuvastatin monotherapy in patients with metabolic syndrome
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DOI：
10.3748/wjg.v21.i25.7860
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发表时间：
2015-07-07
影响因子：
4.3
通讯作者：
Mikhailidis, Dimitri P.
中科院分区：
文献类型：
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作者：
Kargiotis, Konstantinos;Athyros, Vasilios G.;Mikhailidis, Dimitri P.
目的：探讨瑞舒伐他汀单药治疗非酒精性脂肪性肝炎（NASH）的疗效。目前，对于非酒精性脂肪性肝病或其晚期形式 NASH 尚无有效治疗方法。 方法：这项前瞻性研究纳入了 20 名活检证实患有 NASH、代谢综合征 (MetS) 和血脂异常的患者。在基线时对患者血液的生化参数和肝脏进行超声检查。然后患者接受生活方式建议，并接受为期 12 个月的瑞舒伐他汀（10 毫克/天）单药治疗。研究期间每隔 3 个月对患者进行一次重新评估，在此期间测量血液的生化参数，包括肝酶。研究结束时，对所有 20 名患者进行了重复的肝脏活检和超声检查。每 3 个月评估一次肝酶、空腹血糖、血清肌酐、血清尿酸 (SUA)、超敏 C 反应蛋白 (hsCRP) 和血脂谱的变化。主要终点是 NASH 的消退，次要终点是肝酶和血脂值的变化。 结果：重复肝活检和超声检查显示 19 名患者的 NASH 完全消退，而第 20 名患者在研究期间出现动脉高血压和甘油三酯水平大幅升高，这可能是由于生活方式的改变（包括酗酒），该患者既没有改善也没有恶化。血清丙氨酸转氨酶、天冬氨酸转氨酶和谷氨酰转肽酶在第 3 个治疗个月时恢复正常（方差分析 P < 0.001），而碱性磷酸酶活性在第 6 个治疗个月时恢复正常（方差分析，P = 0.01）。空腹血糖和糖化血红蛋白显着降低（P < 0.001）。治疗第 3 个月时血脂值已正常化。到第 9 个治疗月时，没有患者出现 MetS。研究期间体重指数和腰围保持不变。因此，肝脏病理学和功能的变化应完全归因于瑞舒伐他汀治疗。该研究的局限性在于缺乏对照组。结论：这些研究结果表明瑞舒伐他汀单药疗法可以改善活检证实的 NASH 并在 12 个月内解决 MetS。这些作用以及空腹血糖和 SUA 水平的降低可能会降低 NASH 患者血管和肝脏发病率和死亡率的风险。这些发现需要在更大规模的研究中得到证实。
AIM: To investigate the effect of rosuvastatin monotherapy on non-alcoholic steatohepatitis (NASH). At present there is no effective treatment for non-alcoholic fatty liver disease or its advanced form NASH.METHODS: This prospective study included 20 biopsy proven patients with NASH, metabolic syndrome (MetS) and dyslipidaemia. Biochemical parameters of the blood of the patients and an ultrasonography of the liver were performed at baseline. Then patients received lifestyle advice and were treated for a 12 mo period with rosuvastatin (10 mg/d) monotherapy. Patients were re-evaluated during the study at 3 mo intervals, during which biochemical parameters of the blood were measured including liver enzymes. A repeat biopsy and ultrasonography of the liver were performed at the end of the study in all 20 patients. Changes in liver enzymes, fasting plasma glucose, serum creatinine, serum uric acid (SUA), high sensitivity C reactive protein (hsCRP) and lipid profile were assessed every 3 mo. The primary endpoint was the resolution of NASH and the secondary endpoints were the changes in liver enzyme and lipid values.RESULTS: The repeat liver biopsy and ultrasonography showed complete resolution of NASH in 19 patients, while the 20th, which had no improvement but no deterioration either, developed arterial hypertension and substantial rise in triglyceride levels during the study, probably due to changes in lifestyle including alcohol abuse. Serum alanine transaminase, aspartate transaminase, and.-glutamyl transpeptidase were normalised by the 3rd treatment month (ANOVA P < 0.001), while alkaline phosphatase activities by the 6th treatment month (ANOVA, P = 0.01). Fasting plasma glucose and glycated haemoglobin were significantly reduced (P < 0.001). Lipid values were normalised by the 3rd treatment month. No patient had MetS by the 9th treatment month. Body mass index and waist circumference remained unchanged during the study. Thus, changes in liver pathology and function should be attributed solely to rosuvastatin treatment. A limitation of the study is the absence of a control group.CONCLUSION: These findings suggest that rosuvastatin monotherapy could ameliorate biopsy proven NASH and resolve MetS within 12 mo. These effects and the reduction of fasting plasma glucose and SUA levels may reduce the risk of vascular and liver morbidity and mortality in NASH patients. These findings need confirmation in larger studies.