Betaine for Nonalcoholic Fatty Liver Disease: Results of a Randomized Placebo-Controlled Trial
Betaine for Nonalcoholic Fatty Liver Disease: Results of a Randomized Placebo-Controlled Trial
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DOI：
10.1002/hep.23239
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发表时间：
2009-12-01
期刊：
影响因子：
13.5
通讯作者：
Lindor, Keith D.
中科院分区：
文献类型：
--
作者：
Abdelmalek, Manal F.;Sanderson, Schuyler O.;Lindor, Keith D.
基于动物研究和人类中的初步研究，甜菜碱（同型半胱氨酸再甲基化的甲基供体）可能是非酒精性脂肪性肝炎（NASH）的治疗剂。我们评估了甜菜碱对NASH患者的安全性和有效性，以及甜菜碱是否积极修饰了被假设为“二次打击”的因素和NASH的潜在机制。我们对55例经活检证实的NASH患者进行了随机安慰剂对照研究，这些患者接受口服甜菜碱（每日20 g）或安慰剂治疗12个月。使用配对t检验或Wilcoxon秩检验分析治疗前和治疗后变量。治疗组在基线时相当。在完成研究的35名患者（17名甜菜碱，18名安慰剂）中，34名患者（16名甜菜碱，18名安慰剂）接受了治疗后肝活检。随机分配至甜菜碱组的患者脂肪变性等级降低。非酒精性脂肪性肝病活动性评分或纤维化分期未发现组内或组间差异或变化。在NASH患者中观察到的胰岛素、葡萄糖和促炎细胞因子的升高以及抗氧化状态的降低并没有通过甜菜碱治疗得到改善。两组的抗炎剂脂联素均显著降低，且不随治疗而改变。最后，S-腺苷高半胱氨酸大约是正常的两倍，甜菜碱治疗没有减少。结论：与安慰剂相比，甜菜碱改善了肝脏脂肪变性，并可能防止脂肪变性恶化。高剂量甜菜碱补充剂未能减少S-腺苷高半胱氨酸，也没有积极影响任何第二次打击机制，假设有助于NASH，我们研究。尽管甜菜碱已被证明在几种动物模型中有效治疗肝脂肪变性，但将动物研究中发现的新治疗选择转化为NASH患者将具有挑战性。（《肝脏病学》2009年;50：1818-1826）
Based on animal studies and pilot studies in humans, betaine, a methyl donor for the remethylation of homocysteine, may be a therapeutic agent for nonalcoholic steatohepatitis (NASH). We evaluated the safety and efficacy of betaine for patients with NASH and whether betaine positively modified factors postulated to be "second hits" and underlying mechanisms of NASH. We conducted a randomized placebo-control study of 55 patients with biopsy-proven NASH who received either oral betaine (20 g daily) or placebo for 12 months. Pre- and posttreatment variables were analyzed using the paired t test or Wilcoxon rank test. Treatment groups were comparable at baseline. Of the 35 patients (17 betaine, 18 placebo) who completed the study, 34 patients (16 betaine, 18 placebo) underwent posttreatment liver biopsy. Patients randomized to betaine had a decrease in steatosis grade. No intra- or intergroup differences or changes in nonalcoholic fatty liver disease activity score or fibrosis stage were noted. Elevations of insulin, glucose, and proinflammatory cytokines and the reduced antioxidant status noted in NASH patients did not improve with betaine therapy. The anti inflammatory agent adiponectin was significantly reduced in both groups and did not change with therapy. Lastly, S-adenosylhomocysteine was approximately twice normal and was not reduced by betaine therapy. Conclusion: Compared to placebo, betaine improved hepatic steatosis and may protect against worsening steatosis. High-dose betaine supplementation failed to reduce S-adenosylhomocysteine and did not positively affect any of the second hit mechanisms postulated to contribute to NASH that we studied. Although betaine has been proven effective in treating hepatic steatosis in several animal models, translating novel therapeutic options noted in animal studies to humans with NASH will prove challenging. (HEPATOLOGY 2009;50:1818-1826.)